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Akos Czibere - One of the best experts on this subject based on the ideXlab platform.
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A phase 1 study combining the HER3 antibody Seribantumab (MM-121) and cetuximab with and without irinotecan
Investigational New Drugs, 2017Co-Authors: James M. Cleary, Autumn J. Mcree, Geoffrey I. Shapiro, Sara M. Tolaney, Bert H. O’neil, Jeffrey D. Kearns, Sara Mathews, Rachel Nering, Gavin Macbeath, Akos CzibereAbstract:Background HER3/EGFR heterodimers have been implicated as a mode of resistance to EGFR-directed therapies. Methods This Phase 1 trial assessed the tolerability, maximum tolerated dose (MTD) and pharmacokinetic (PK) properties of the HER-3 antibody Seribantumab in combination with cetuximab (Part I) or cetuximab and irinotecan (Part II) in patients with EGFR-dependent cancers. In Part I, escalating doses of Seribantumab and cetuximab were administered. In Part II of the trial, escalating doses of Seribantumab/cetuximab were combined with irinotecan 180 mg/m2 administered every two weeks. Results 34 patients were enrolled in Part I (Seribantumab/cetuximab) and 14 patients were enrolled in Part II (Seribantumab/cetuximab/irinotecan). Common toxicities of Seribantumab/cetuximab included acneiform rash, diarrhea, stomatitis, and paronychia. The MTD of Part I was Seribantumab 40 mg/kg bolus, then 20 mg/kg weekly combined with cetuximab 400 mg / m2 bolus, then 250 mg / m2 IV weekly. Common toxicities reported in the Seribantumab/cetuximab/irinotecan combination were similar to the Part I portion. However, toxicities were more frequent and severe with the triplet combination. There was one treatment-related death in Part II secondary to Grade 4 neutropenia and grade 3 diarrhea. Other dose-limiting toxicities in Part II were Grade 3 mucositis and Grade 3 diarrhea. A cholangiocarcinoma patient, previously untreated with EGFR-directed therapy, had a confirmed partial response (PR). One colorectal cancer patient, previously treated with EGFR-directed therapy, had an unconfirmed PR. Conclusions Seribantumab/cetuximab was well tolerated and patients experienced toxicities typical to EGFR inhibition. Unlike the Seribantumab/cetuximab doublet, Seribantumab/cetuximab/irinotecan was difficult to tolerate in this heavily pretreated population. There was limited efficacy of the combination therapy.
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abstract a14 a randomized trial of exemestane Seribantumab mm 121 in postmenopausal women with locally advanced or metastatic er pr her2 breast cancer final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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Abstract A14: A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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abstract a19 identification of heregulin hrg expression as a driver of a difficult to treat cancer phenotype and development of a companion diagnostic for the hrg erbb3 targeting drug Seribantumab
Clinical Cancer Research, 2017Co-Authors: Sara Mathews, Gavin Macbeath, Akos Czibere, Arthur J Kudla, Gregory J Finn, Victoria Rimkunas, Peter Laivins, Jason BaumAbstract:Heregulin (HRG) is the cognate ligand of the ErbB3 receptor and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Seribantumab (MM-121) is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and to prevent the establishment of HRG-driven cancer cell survival in response to cytotoxic therapies. Clinical evidence from randomized studies suggests that patients who receive standard therapy have shorter progression-free survival (PFS) when their tumors are positive for HRG RNA expression compared to patients receiving standard therapy with HRG-negative tumors. The addition of Seribantumab was able to enhance the anti-tumor effect of these respective standard therapies and prolong PFS in patients with HRG-positive tumors. Profiling data indicates that positive HRG expression can be found in more than a third of most solid tumors identifying a high unmet medical need. In order to identify HRG-driven tumors with a more difficult-to-treat phenotype, an RNA in situ hybridization (ISH) diagnostic assay has been developed. Details will be presented illustrating the benefits of RNA ISH over alternate detection methods for HRG. This includes the visualization of tumor cell HRG expression with high sensitivity and specificity in small tissue specimens such as fine needle aspirates and core needle biopsies. This assay is currently being used to select patients for inclusion into diagnostic-driven clinical studies. Citation Format: Sara Mathews, Gregory Finn, Arthur J. Kudla, Victoria Rimkunas, Peter Laivins, Gavin MacBeath, Akos Czibere, Jason Baum. Identification of Heregulin (HRG) expression as a driver of a difficult-to-treat cancer phenotype and development of a companion diagnostic for the HRG-ErbB3 targeting drug Seribantumab. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A19.
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traitements combines avec Seribantumab
2016Co-Authors: Bambang Adiwijaya, Rachel Nering, Akos Czibere, Gavin MacbeathAbstract:La presente invention concerne des compositions et des methodes pour traiter un cancer chez un patient humain selectionne, lesdites methodes consistant a administrer au patient une combinaison d'un anticorps anti-ErbB3 (par exemple, Seribantumab) et un second medicament anti-cancer. Les cancers a traiter par les methodes et les compositions selon l'invention comprennent des cancers qui sont positifs a l'hereguline (HRG).
Sara Mathews - One of the best experts on this subject based on the ideXlab platform.
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abstract ot3 06 01 sherboc a double blind placebo controlled phase 2 trial of Seribantumab mm 121 plus fulvestrant in postmenopausal women with hormone receptor positive heregulin positive her2 negative metastatic breast cancer whose disease progress
Cancer Research, 2018Co-Authors: P A Kaufman, Sara Mathews, M Pipas, G J Finn, Hong Zhang, J Richards, Arthur J Kudla, T Bloom, A A Zalutskaya, J LlorinsangalangAbstract:Background: The receptor tyrosine kinase, HER3 and its ligand, heregulin (HRG), have been implicated in the initiation and progression of multiple cancer types including: breast, lung, and head & neck cancers. Seribantumab is a fully human, monoclonal IgG2 antibody that binds to the ligand-binding domain of HER3 and inhibits HRG-mediated signaling. Previously, Seribantumab was tested in combination with exemestane in a placebo-controlled, Phase 2 study in post-menopausal women with ER/PR+, HER2 negative metastatic breast cancer (mBC). Although the trial failed to meet its primary efficacy objective of a 50% reduction in hazard ratio in the Seribantumab/exemestane treatment vs. the placebo/exemestane control group, a positive trend in PFS and a statistically significant improvement in median OS was observed in patients in the Seribantumab/exemestane treatment group. Seribantumab has also been tested in three randomized Phase 2 studies adding to standard of care (SOC) in non-small cell lung, ER/PR+ mBC, and platinum resistant/refractory ovarian cancer. These studies were retrospectively analyzed to determine correlation between HRG mRNA levels in tumor tissue and PFS. In each of these studies, the presence of tumor cell HRG mRNA was prognostic for shortened PFS with SOC treatment. Further, the addition of Seribantumab to SOC therapy improved PFS for patients with HRG+ tumors. These data support the hypothesis that HRG expression may define a drug tolerant cancer cell phenotype characterized by poor response to multiple classes of cytotoxic and targeted therapies, including aromatase inhibitors and SERDs. Additionally, blockade of HRG-induced HER3 signaling by Seribantumab may counter such protective effects of HRG on cancer cells, with the potential for improved outcomes in HRG+ patients. It is estimated that ˜45% of hormone-receptor positive, HER2 negative advanced breast cancers are HRG+ and that HRG expression may contribute to accelerated clinical progression observed in this subset of patients. Trial design: In the upcoming randomized, double-blinded, multi-center, Phase 2 study, ER/PR receptor-positive, HER2 negative mBC patients with HRG+ tumors will be prospectively selected using a HRG RNA in situ hybridization assay. Approximately 200 women will be screened to enroll 80 HRG+ subjects. Eligible subjects will be randomized in a 1:1 ratio to receive Seribantumab/fulvestrant or placebo/fulvestrant until investigator-assessed disease progression or unacceptable toxicity, whichever comes first. Subjects will have progressed on one or two prior hormonal therapies, one of which must have been a CDKi-containing regimen. The goal of this study is to determine if the combination of Seribantumab + fulvestrant is more effective than placebo + fulvestrant based on PFS (primary end point) in HRG positive subjects. Secondary endpoints include OS, objective response rate, and time to progression. Safety will also be assessed. Enrollment is expected to begin in 2017 at approximately 80 sites globally. Citation Format: Kaufman PA, Pipas M, Finn GJ, Mathews SE, Zhang H, Richards J, Kudla AJ, Bloom T, Zalutskaya AA, Llorin-Sangalang J, Pinto AC, Ettl J. SHERBOC: A double-blind, placebo-controlled, phase 2 trial of Seribantumab (MM-121) plus fulvestrant in postmenopausal women with hormone receptor-positive, heregulin positive, HER2 negative metastatic breast cancer whose disease progressed after prior systemic therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-06-01.
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A phase 1 study combining the HER3 antibody Seribantumab (MM-121) and cetuximab with and without irinotecan
Investigational New Drugs, 2017Co-Authors: James M. Cleary, Autumn J. Mcree, Geoffrey I. Shapiro, Sara M. Tolaney, Bert H. O’neil, Jeffrey D. Kearns, Sara Mathews, Rachel Nering, Gavin Macbeath, Akos CzibereAbstract:Background HER3/EGFR heterodimers have been implicated as a mode of resistance to EGFR-directed therapies. Methods This Phase 1 trial assessed the tolerability, maximum tolerated dose (MTD) and pharmacokinetic (PK) properties of the HER-3 antibody Seribantumab in combination with cetuximab (Part I) or cetuximab and irinotecan (Part II) in patients with EGFR-dependent cancers. In Part I, escalating doses of Seribantumab and cetuximab were administered. In Part II of the trial, escalating doses of Seribantumab/cetuximab were combined with irinotecan 180 mg/m2 administered every two weeks. Results 34 patients were enrolled in Part I (Seribantumab/cetuximab) and 14 patients were enrolled in Part II (Seribantumab/cetuximab/irinotecan). Common toxicities of Seribantumab/cetuximab included acneiform rash, diarrhea, stomatitis, and paronychia. The MTD of Part I was Seribantumab 40 mg/kg bolus, then 20 mg/kg weekly combined with cetuximab 400 mg / m2 bolus, then 250 mg / m2 IV weekly. Common toxicities reported in the Seribantumab/cetuximab/irinotecan combination were similar to the Part I portion. However, toxicities were more frequent and severe with the triplet combination. There was one treatment-related death in Part II secondary to Grade 4 neutropenia and grade 3 diarrhea. Other dose-limiting toxicities in Part II were Grade 3 mucositis and Grade 3 diarrhea. A cholangiocarcinoma patient, previously untreated with EGFR-directed therapy, had a confirmed partial response (PR). One colorectal cancer patient, previously treated with EGFR-directed therapy, had an unconfirmed PR. Conclusions Seribantumab/cetuximab was well tolerated and patients experienced toxicities typical to EGFR inhibition. Unlike the Seribantumab/cetuximab doublet, Seribantumab/cetuximab/irinotecan was difficult to tolerate in this heavily pretreated population. There was limited efficacy of the combination therapy.
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abstract a14 a randomized trial of exemestane Seribantumab mm 121 in postmenopausal women with locally advanced or metastatic er pr her2 breast cancer final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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Abstract A14: A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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abstract a19 identification of heregulin hrg expression as a driver of a difficult to treat cancer phenotype and development of a companion diagnostic for the hrg erbb3 targeting drug Seribantumab
Clinical Cancer Research, 2017Co-Authors: Sara Mathews, Gavin Macbeath, Akos Czibere, Arthur J Kudla, Gregory J Finn, Victoria Rimkunas, Peter Laivins, Jason BaumAbstract:Heregulin (HRG) is the cognate ligand of the ErbB3 receptor and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Seribantumab (MM-121) is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and to prevent the establishment of HRG-driven cancer cell survival in response to cytotoxic therapies. Clinical evidence from randomized studies suggests that patients who receive standard therapy have shorter progression-free survival (PFS) when their tumors are positive for HRG RNA expression compared to patients receiving standard therapy with HRG-negative tumors. The addition of Seribantumab was able to enhance the anti-tumor effect of these respective standard therapies and prolong PFS in patients with HRG-positive tumors. Profiling data indicates that positive HRG expression can be found in more than a third of most solid tumors identifying a high unmet medical need. In order to identify HRG-driven tumors with a more difficult-to-treat phenotype, an RNA in situ hybridization (ISH) diagnostic assay has been developed. Details will be presented illustrating the benefits of RNA ISH over alternate detection methods for HRG. This includes the visualization of tumor cell HRG expression with high sensitivity and specificity in small tissue specimens such as fine needle aspirates and core needle biopsies. This assay is currently being used to select patients for inclusion into diagnostic-driven clinical studies. Citation Format: Sara Mathews, Gregory Finn, Arthur J. Kudla, Victoria Rimkunas, Peter Laivins, Gavin MacBeath, Akos Czibere, Jason Baum. Identification of Heregulin (HRG) expression as a driver of a difficult-to-treat cancer phenotype and development of a companion diagnostic for the HRG-ErbB3 targeting drug Seribantumab. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A19.
Gavin Macbeath - One of the best experts on this subject based on the ideXlab platform.
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A phase 1 study combining the HER3 antibody Seribantumab (MM-121) and cetuximab with and without irinotecan
Investigational New Drugs, 2017Co-Authors: James M. Cleary, Autumn J. Mcree, Geoffrey I. Shapiro, Sara M. Tolaney, Bert H. O’neil, Jeffrey D. Kearns, Sara Mathews, Rachel Nering, Gavin Macbeath, Akos CzibereAbstract:Background HER3/EGFR heterodimers have been implicated as a mode of resistance to EGFR-directed therapies. Methods This Phase 1 trial assessed the tolerability, maximum tolerated dose (MTD) and pharmacokinetic (PK) properties of the HER-3 antibody Seribantumab in combination with cetuximab (Part I) or cetuximab and irinotecan (Part II) in patients with EGFR-dependent cancers. In Part I, escalating doses of Seribantumab and cetuximab were administered. In Part II of the trial, escalating doses of Seribantumab/cetuximab were combined with irinotecan 180 mg/m2 administered every two weeks. Results 34 patients were enrolled in Part I (Seribantumab/cetuximab) and 14 patients were enrolled in Part II (Seribantumab/cetuximab/irinotecan). Common toxicities of Seribantumab/cetuximab included acneiform rash, diarrhea, stomatitis, and paronychia. The MTD of Part I was Seribantumab 40 mg/kg bolus, then 20 mg/kg weekly combined with cetuximab 400 mg / m2 bolus, then 250 mg / m2 IV weekly. Common toxicities reported in the Seribantumab/cetuximab/irinotecan combination were similar to the Part I portion. However, toxicities were more frequent and severe with the triplet combination. There was one treatment-related death in Part II secondary to Grade 4 neutropenia and grade 3 diarrhea. Other dose-limiting toxicities in Part II were Grade 3 mucositis and Grade 3 diarrhea. A cholangiocarcinoma patient, previously untreated with EGFR-directed therapy, had a confirmed partial response (PR). One colorectal cancer patient, previously treated with EGFR-directed therapy, had an unconfirmed PR. Conclusions Seribantumab/cetuximab was well tolerated and patients experienced toxicities typical to EGFR inhibition. Unlike the Seribantumab/cetuximab doublet, Seribantumab/cetuximab/irinotecan was difficult to tolerate in this heavily pretreated population. There was limited efficacy of the combination therapy.
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abstract a14 a randomized trial of exemestane Seribantumab mm 121 in postmenopausal women with locally advanced or metastatic er pr her2 breast cancer final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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Abstract A14: A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis
Clinical Cancer Research, 2017Co-Authors: Greg Finn, Art Kudla, Sara Mathews, Gavin Macbeath, Hong Zhang, Anna Blois, Jason Baum, Mike Cieslewicz, Bambang Adiwijaya, Akos CzibereAbstract:Heregulin (HRG) is the cognate ligand of the human epidermal growth factor receptor 3 (ErbB3) and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Preclinical studies indicate that not only can HRG induce proliferation of cellular cancer models but also that it can mediate insensitivity to numerous classes of anticancer agents including chemotherapies and targeted therapeutics. Furthermore, we and others have found that HRG-ErbB3 signaling is adept at mediating insensitivity to several classes of anti-hormonal agents that currently represent the mainstay of treatment options for hormone receptor (HR+), HER2 negative advanced breast cancer. This finding, coupled with the fact that HRG is expressed in almost half of all HR+, HER2 negative advanced breast cancers, indicates that HRG-ErbB3 signal transduction may be contributing to loss of sensitivity to endocrine based therapies in this disease. Mechanistically, anti-hormonal drugs including, fulvestrant have been implicated in increasing ErbB3 expression levels, resulting in a compensatory mechanism where cells become resistant to endocrine treatments due to estrogen independent proliferation. Seribantumab is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and prevent the establishment of HRG-driven cancer cell survival in response to standard of care therapies, including chemotherapies and anti-endocrine therapies. Clinical results from a randomized, Phase 2 study in women with metastatic breast cancer who received Seribantumab plus exemestane or placebo plus exemestane highlighted the ability to sensitize HRG-positive tumors to exemestane by co-administration with Seribantumab. Overall, data indicated that there was a positive trend in prolonging progression-free survival (PFS) and a statistically significant difference in overall survival (OS) in this randomized and unselected or “all-comers” patient population for those patients who had Seribantumab added to their exemestane therapy rather than placebo. Safety analysis indicated that Seribantumab plus exemestane was well tolerated, with manageable diarrhea being the most frequent adverse event observed. A preplanned biomarker analysis using archived tissue samples showed that women who have HRG-positive tumors were less sensitive to exemestane alone and derived substantial clinical benefit when receiving the combination of Seribantumab plus exemestane, illustrated by a statistically significant improvement in PFS in this HRG-positive population. Further clinical subgroup analysis suggested that patients who received prior chemotherapy and patients whose disease had progressed in the metastatic setting may be more likely to benefit from the addition of Seribantumab to their exemestane. To identify patients with HRG-driven cancers, an RNA in situ hybridization (ISH) diagnostic assay has been developed and is currently being utilized to select patients in a Phase 2 non-small cell lung cancer trial. We will present updates on clinical outcomes based on recent patient subgroup analyses along with a clinical development plan for Seribantumab in HR+, HER2- advanced breast cancer. Citation Format: Greg Finn, Hong Zhang, Anna Blois, sara Mathews, Art Kudla, Jason Baum, Mike Cieslewicz, gavin macbeath, Bambang Adiwijaya, Akos Czibere. A randomized trial of exemestane +/- Seribantumab (MM-121) in postmenopausal women with locally advanced or metastatic ER/PR+ HER2- breast cancer: Final analysis and extended subgroup analysis. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A14.
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abstract a19 identification of heregulin hrg expression as a driver of a difficult to treat cancer phenotype and development of a companion diagnostic for the hrg erbb3 targeting drug Seribantumab
Clinical Cancer Research, 2017Co-Authors: Sara Mathews, Gavin Macbeath, Akos Czibere, Arthur J Kudla, Gregory J Finn, Victoria Rimkunas, Peter Laivins, Jason BaumAbstract:Heregulin (HRG) is the cognate ligand of the ErbB3 receptor and has been identified as a potent driver of a distinct tumor cell phenotype characterized by enhanced survival that appears to be inherently more resistant to standard of care therapies. Seribantumab (MM-121) is a fully human monoclonal antibody designed to block HRG from binding to ErbB3 and to prevent the establishment of HRG-driven cancer cell survival in response to cytotoxic therapies. Clinical evidence from randomized studies suggests that patients who receive standard therapy have shorter progression-free survival (PFS) when their tumors are positive for HRG RNA expression compared to patients receiving standard therapy with HRG-negative tumors. The addition of Seribantumab was able to enhance the anti-tumor effect of these respective standard therapies and prolong PFS in patients with HRG-positive tumors. Profiling data indicates that positive HRG expression can be found in more than a third of most solid tumors identifying a high unmet medical need. In order to identify HRG-driven tumors with a more difficult-to-treat phenotype, an RNA in situ hybridization (ISH) diagnostic assay has been developed. Details will be presented illustrating the benefits of RNA ISH over alternate detection methods for HRG. This includes the visualization of tumor cell HRG expression with high sensitivity and specificity in small tissue specimens such as fine needle aspirates and core needle biopsies. This assay is currently being used to select patients for inclusion into diagnostic-driven clinical studies. Citation Format: Sara Mathews, Gregory Finn, Arthur J. Kudla, Victoria Rimkunas, Peter Laivins, Gavin MacBeath, Akos Czibere, Jason Baum. Identification of Heregulin (HRG) expression as a driver of a difficult-to-treat cancer phenotype and development of a companion diagnostic for the HRG-ErbB3 targeting drug Seribantumab. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Targeting the Vulnerabilities of Cancer; May 16-19, 2016; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(1_Suppl):Abstract nr A19.
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traitements combines avec Seribantumab
2016Co-Authors: Bambang Adiwijaya, Rachel Nering, Akos Czibere, Gavin MacbeathAbstract:La presente invention concerne des compositions et des methodes pour traiter un cancer chez un patient humain selectionne, lesdites methodes consistant a administrer au patient une combinaison d'un anticorps anti-ErbB3 (par exemple, Seribantumab) et un second medicament anti-cancer. Les cancers a traiter par les methodes et les compositions selon l'invention comprennent des cancers qui sont positifs a l'hereguline (HRG).
Lecia V. Sequist - One of the best experts on this subject based on the ideXlab platform.
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randomized phase ii trial of Seribantumab in combination with erlotinib in patients with egfr wild type non small cell lung cancer
Oncologist, 2019Co-Authors: Lecia V. Sequist, Jhanelle E. Gray, Wael A Harb, Ariel Lopezchavez, Robert C Doebele, Manuel R Modiano, David M Jackman, Maria Q Baggstrom, Akin Atmaca, Enriqueta FelipAbstract:BACKGROUND Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3) to block heregulin (HRG/NRG)-mediated ErbB3 signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of Seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of Seribantumab plus erlotinib, versus erlotinib alone, in patients with EGFR wild-type tumors and describe the potential predictive power of HRG. MATERIALS AND METHODS Patients with EGFR wild-type NSCLC were assigned randomly to receive Seribantumab + erlotinib or erlotinib alone. Patients underwent pretreatment core needle biopsy and archived tumor samples were collected to support prespecified biomarker analyses. RESULTS One hundred twenty-nine patients received Seribantumab + erlotinib (n = 85) or erlotinib alone (n = 44). Median estimated progression-free survival (PFS) in the unselected intent-to-treat (ITT) population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (hazard ratio [HR], 0.822; 95% confidence interval [CI], 0.37-1.828; p = 0.63), and median estimated overall survival was 27.3 and 40.3 weeks in the experimental and control arm, respectively (HR, 1.395; 95% CI, 0.846 to 2.301; p = .1898) In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the Seribantumab + erlotinib combination (HR, 0.35; 95% CI, 0.16-0.76; p = .008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97-4.76; p = .059, HRG-by-treatment interaction, p value = .0016). CONCLUSION The addition of Seribantumab to erlotinib did not result in improved PFS in unselected patients. However, predefined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from Seribantumab. An ongoing clinical trial of Seribantumab, in combination with docetaxel, is underway in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216). IMPLICATIONS FOR PRACTICE The poor prognosis of patients with non-small cell lung cancer (NSCLC) underscores the need for more effective treatment options, highlighting the unmet medical need in this patient population. The results of this study show that a novel biomarker, heregulin, may help to identify patients with advanced NSCLC who could benefit from treatment with Seribantumab. On the basis of the observed safety profile and promising clinical efficacy, a prospective, randomized, open-label, international, multicenter phase II trial (SHERLOC, NCT02387216) is under way to investigate the efficacy and safety of Seribantumab in combination with docetaxel in patients with heregulin-positive advanced adenocarcinoma.
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SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).
Journal of Clinical Oncology, 2019Co-Authors: Lecia V. Sequist, Pasi A. Jänne, Rudolf M. Huber, Jhanelle E. Gray, Enriqueta Felip, Maurice Pérol, Fred R. Hirsch, Geoffrey Kuesters, Alena ZalutskayaAbstract:9036Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that Seribantumab reverses HRG mediated drug resistance across...
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evaluation of fixed dose regimens of Seribantumab in patients with solid tumors
Journal of Clinical Oncology, 2018Co-Authors: Bambang Adiwijaya, Lecia V. Sequist, Walid S Kamoun, Sara Ghassemifar, Sergio Santillana, Peter A Kaufman, Johannes Ettl, M Higgins, Marc J PipasAbstract:2524Background: Seribantumab (MM-121) is an anti-ErbB3 human monoclonal antibody being tested as an anti-cancer therapy for patients with high expression of heregulin mRNA in NSCLC (SHERLOC study, ...
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a phase 2 study of Seribantumab mm 121 in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive hrg locally advanced or metastatic non small cell lung cancer nsclc
Journal of Clinical Oncology, 2016Co-Authors: Lecia V. Sequist, Art Kudla, Sara Mathews, Rudolf M. Huber, Enriqueta Felip, Wael A Harb, Ian Anderson, Nathan Demars, Ty Mcclure, Jorge NievaAbstract:TPS9110Background: The role of the HER3 receptor and its ligand heregulin (HRG) in the progression of multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal ...
Enriqueta Felip - One of the best experts on this subject based on the ideXlab platform.
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randomized phase ii trial of Seribantumab in combination with erlotinib in patients with egfr wild type non small cell lung cancer
Oncologist, 2019Co-Authors: Lecia V. Sequist, Jhanelle E. Gray, Wael A Harb, Ariel Lopezchavez, Robert C Doebele, Manuel R Modiano, David M Jackman, Maria Q Baggstrom, Akin Atmaca, Enriqueta FelipAbstract:BACKGROUND Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3) to block heregulin (HRG/NRG)-mediated ErbB3 signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of Seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of Seribantumab plus erlotinib, versus erlotinib alone, in patients with EGFR wild-type tumors and describe the potential predictive power of HRG. MATERIALS AND METHODS Patients with EGFR wild-type NSCLC were assigned randomly to receive Seribantumab + erlotinib or erlotinib alone. Patients underwent pretreatment core needle biopsy and archived tumor samples were collected to support prespecified biomarker analyses. RESULTS One hundred twenty-nine patients received Seribantumab + erlotinib (n = 85) or erlotinib alone (n = 44). Median estimated progression-free survival (PFS) in the unselected intent-to-treat (ITT) population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (hazard ratio [HR], 0.822; 95% confidence interval [CI], 0.37-1.828; p = 0.63), and median estimated overall survival was 27.3 and 40.3 weeks in the experimental and control arm, respectively (HR, 1.395; 95% CI, 0.846 to 2.301; p = .1898) In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the Seribantumab + erlotinib combination (HR, 0.35; 95% CI, 0.16-0.76; p = .008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97-4.76; p = .059, HRG-by-treatment interaction, p value = .0016). CONCLUSION The addition of Seribantumab to erlotinib did not result in improved PFS in unselected patients. However, predefined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from Seribantumab. An ongoing clinical trial of Seribantumab, in combination with docetaxel, is underway in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216). IMPLICATIONS FOR PRACTICE The poor prognosis of patients with non-small cell lung cancer (NSCLC) underscores the need for more effective treatment options, highlighting the unmet medical need in this patient population. The results of this study show that a novel biomarker, heregulin, may help to identify patients with advanced NSCLC who could benefit from treatment with Seribantumab. On the basis of the observed safety profile and promising clinical efficacy, a prospective, randomized, open-label, international, multicenter phase II trial (SHERLOC, NCT02387216) is under way to investigate the efficacy and safety of Seribantumab in combination with docetaxel in patients with heregulin-positive advanced adenocarcinoma.
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SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).
Journal of Clinical Oncology, 2019Co-Authors: Lecia V. Sequist, Pasi A. Jänne, Rudolf M. Huber, Jhanelle E. Gray, Enriqueta Felip, Maurice Pérol, Fred R. Hirsch, Geoffrey Kuesters, Alena ZalutskayaAbstract:9036Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that Seribantumab reverses HRG mediated drug resistance across...
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a phase 2 study of Seribantumab mm 121 in combination with docetaxel or pemetrexed versus docetaxel or pemetrexed alone in patients with heregulin positive hrg locally advanced or metastatic non small cell lung cancer nsclc
Journal of Clinical Oncology, 2016Co-Authors: Lecia V. Sequist, Art Kudla, Sara Mathews, Rudolf M. Huber, Enriqueta Felip, Wael A Harb, Ian Anderson, Nathan Demars, Ty Mcclure, Jorge NievaAbstract:TPS9110Background: The role of the HER3 receptor and its ligand heregulin (HRG) in the progression of multiple cancers has been well established. Seribantumab (MM-121) is a fully human, monoclonal ...
