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David A Reardon - One of the best experts on this subject based on the ideXlab platform.
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Rindopepimut with bevacizumab for patients with relapsed egfrviii expressing glioblastoma react results of a double blind randomized phase ii trial
Clinical Cancer Research, 2020Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Donald M Orourke, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S AshbyAbstract:Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of Rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naive patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive Rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 Rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for Rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the Rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of Rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
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imct 08react long term survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:BACKGROUND: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of an EGFRvIII-specific peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety. METHODS: In the Phase II “ReACT” study, 73 bevacizumab (BV)-naive pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary; target α = 0.2 by 1-sided chi-square test), objective response rate (ORR), PFS, OS and safety. RESULTS: Primary Rindopepimut toxicity is Grade 1-2 injection site reaction. For Rindopepimut + BV vs. KLH + BV (per centralized review; RANO criteria): PFS6 = 28% (10/36) vs. 16% (6/37) (p = 0.116); ORR = 30% (9/30) vs. 18% (6/34). Cessation of steroids > 2 months: 44% (8/18) vs 21% (4/19), >6 months: 33% (6/18) vs. 0. Median (95% CI) OS = 11.6 (10.0, 16.2) vs. 9.3 (7.1, 11.3) months (HR = 0.57 [0.33, 0.98], p = 0.039). 9 vs 6 pts remain in follow-up; 6 vs. 2 are progression-free. OS analyses adjusted for various prognostic factors consistently favor Rindopepimut. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Antibodies, predominantly IgG1 isotype, mediate killing of EGFRvIII+ tumor cells through ADCC and CDCC in vitro. Within the Rindopepimut arm, peak titer (≥1:12,800 at any time) and rapid titer generation (≥1:12,800 by Day 57) were associated with prolonged OS (HR = 0.16, p = <0.0001 and HR = 0.59, p = 0.182, respectively). Evaluation of humoral response quality, HLA typing vs. outcome, and survival follow-up continue. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. CONCLUSIONS: Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.
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107 react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neurosurgery, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:Author(s): Reardon, DA; Schuster, JM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Desjardins, A; Ashby, LS; Duic, JP; Mrugala, MM; Werner, A; Hawthorne, T; He, Y; Green, J; Yellin, MJ; Turner, CD; Davis, TA; Sampson, JH | Abstract: INTRODUCTION: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with granulocyte macrophage colony-stimulating factor. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS), and safety profile. Compassionate-use experience suggests that Rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV). METHODS: In the Phase II "ReACT" study, BV-naive patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). END POINTS: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety. RESULTS: Accrual is complete (n = 72); study follow-up continues (n = 30). Primary Rindopepimut toxicity is grade 1 to 2 injection site reaction. For Rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side χ test); ORR = 24% (7/29) vs 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; P = .0208), with 8 vs 4 patients progression-free. OS analyses favor Rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the Rindopepimut arm, and was most frequent in patients with KPS ≥ 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response. CONCLUSION: These near-final data show that Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV in patients with relapsed GB.
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Rindopepimut vaccine and bevacizumab combination therapy improving survival rates in relapsed glioblastoma patients
Immunotherapy, 2015Co-Authors: Martha R Neagu, David A ReardonAbstract:Glioblastoma (GBM), the most common malignant primary tumor in adults, carries a dismal prognosis. Median overall survival (OS) following currently available standard therapy for newly diagnosed patients, which includes maximal safe resection followed by fractionated radiotherapy plus concurrent and adjuvant temozolomide is under 15 months [1] and has failed to improve despite recently reported randomized Phase III studies evaluating dose dense temozolomide [2], VEGF blockade [3,4] and anti-integrin therapy [5]. Effective therapy for patients following recurrence has been even more problematic. Although the genetic complexity of GBM tumors has recently been elegantly articulated [6,7], exploitation of this information using targeted molecular therapeutics in multiple clinical studies has been uniformly disappointing to date [8]. Furthermore, although GBM tumors are highly angiogenic and express high levels of VEGF; VEGF targeting therapeutics such as bevacizumab have modestly improved progression-free survival at best for recurrent patients [9]. Therapeutics capable of improving OS for GBM have remained elusive, underscoring the critical need for innovative treatment approaches for this major unmet need in oncology. A variety of immunotherapy approaches, including cancer vaccines, immune checkpoint blockade and chimeric antigen receptor T cells, have recently demonstrated exciting benefit across a spectrum of cancers. Nonetheless, the role of these agents for GBM patients remains undefined [10]. Furthermore, many speculate that immunotherapies are unlikely to be of value for GBM patients based on historical dogma supporting immuno privilege of the CNS. Despite this bias, growing data argues against the concept of CNS immunosanctity, and in fact demonstrates that a dynamic and effective interaction exists between the CNS and systemic immune systems. Accordingly, a wide array of immune-based therapies is currently under clinical evaluation for GBM patients. The most advanced immuno therapeutic in the clinical arena for GBM patients is Rindopepimut, a peptide vaccine targeting EGFRvIII. In contrast to early GBM vaccines utilizing either whole tumor lysate or tumor-associated antigen (TAA) cocktail approaches, Rindopepimut was developed to attack EGFRvIII, a target that is exquisitely tumor specific. EGFRvIII is present in approximately 30% of GBM tumors and can be readily detected by available immunohistochemistry or RT-PCR assays. EGFRvIII results from an in-frame deletion of exons 2–7 that leads to the physical approximation of two normally separated portions of Rindopepimut vaccine and bevacizumab combination therapy: improving survival rates in relapsed glioblastoma patients?
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a phase ii multicenter trial of Rindopepimut cdx 110 in newly diagnosed glioblastoma the act iii study
Neuro-oncology, 2015Co-Authors: James M Schuster, Lawrence Recht, David A Reardon, Rose Lai, Nina Paleologos, Morris D GrovesAbstract:The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, results in a constitutively activated receptor with a novel, highly immunogenic extracelluar epitope. EGFRvIII is present in 25%–30% of glioblastomas1 but is not significantly expressed in healthy tissue. Expression of EGFRvIII correlates with increased tumorigenicity in mouse models.2 In glioblastoma, EGFRvIII has been associated with poor long-term survival, independent of other known significant prognostic factors, such as gross total resection (GTR).3–6 EGFRvIII expression is often heterogeneous in glioblastoma specimens, but EGFRvIII+ cells may influence neighboring EGFRvIII–tumor cells through cytokines and microvesicles, providing a proliferative signal even to nonexpressing cells.7–9 EGFRvIII is also frequently expressed in glioblastoma tumor stem cells.10,11 EGFRvIII and isocitrate dehydrogenase (IDH) 1/2 mutations, the latter associated with long-term survival, rarely coexist in the same patient.12,13 Rindopepimut vaccine consists of the unique 13 amino acid sequence created by the in-frame deletion of EGFRvIII, chemically conjugated to keyhole limpet hemocyanin (KLH) as described by Heimberger and colleagues.14 Rindopepimut is designed to generate a specific immune response against EGFRvIII+ tumor cells, an approach which may be particularly relevant for glioblastoma, where diffuse infiltration of tumor into healthy white matter presents a treatment challenge. Preclinical models have demonstrated that induction of humoral and cellular anti-EGFRvIII immune responses can be effective against EGFRvIII+ intracranial tumors.14 In 2 small single-arm phase II trials conducted at MD Anderson and Duke University (“ACTIVATE” and “ACT II”),6,15 Rindopepimut was well tolerated in patients with resected, EGFRvIII+ glioblastoma with promising progression-free survival (PFS) and overall survival (OS) compared with a contemporary cohort of patients matched for major study eligibility. In addition, the vaccine elicited robust anti-EGFRvIII immune responses despite concurrent temozolomide chemotherapy, and EGFRvIII was routinely eliminated in posttreatment tumor samples obtained at recurrence. The current study (“ACT III”) was performed to confirm these results in a larger, multicenter trial.
John H Sampson - One of the best experts on this subject based on the ideXlab platform.
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prospect of Rindopepimut in the treatment of glioblastoma
Expert Opinion on Biological Therapy, 2017Co-Authors: Aladine A Elsamadicy, Pakawat Chongsathidkiet, Rupen Desai, Karolina Woroniecka, Harrison S Farber, Peter E Fecci, John H SampsonAbstract:ABSTRACTIntroduction: Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain – glioblastoma (GBM).Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH). The EGFRvIII neoantigen is exclusively present on GBM cells, providing Rindopepimut tumor-specific activity. The authors review Rindopepimut’s clinical efficacy, administration, safety, and prospects in the treatment of GBM.Expert opinion: Rindopepimut showed clinical benefit and significant efficacy in phase II clinical trials, including as part of a multi-immunot...
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Rindopepimut a promising immunotherapeutic for the treatment of glioblastoma multiforme
Immunotherapy, 2014Co-Authors: Adam M Swartz, John H SampsonAbstract:Glioblastoma multiforme (GBM) is the most common and aggressive glial cell-derived primary tumor. Current standard of care for patients with GBM includes maximal tumor resection plus adjuvant radiotherapy and temozolomide chemotherapy, increasing median overall survival to a mere 15 months from diagnosis. Because these therapies are inherently nonspecific, there is an increased likelihood of off-target and incomplete effects; therefore, targeted modalities are required for enhanced safety and efficacy. Rindopepimut is emerging as a safe and potentially effective drug for the treatment of GBM. Rindopepimut consists of a 14-mer peptide that spans the length of EGF receptor variant III, a mutant variant of EGF receptor found on approximately 30% of primary GBM, conjugated to the carrier protein keyhole limpet hemocyanin. Vaccination with Rindopepimut has been shown to specifically eliminate cells expressing EGF receptor variant III. Phase II clinical trials have suggested that vaccination of newly diagnosed GBM patients with Rindopepimut plus adjuvant granulocyte-macrophage colony-stimulating factor results in prolonged progression-free and overall survival with minimal toxicity. This review will outline the development of Rindopepimut, as well as the current status of this vaccine.
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Rindopepimut anti egfrviii peptide vaccine oncolytic
Drugs of The Future, 2013Co-Authors: Patrick C Gedeon, John H Sampson, Bryan D Choi, Darell D BignerAbstract:Glioblastoma, the most common primary malignant brain tumor, is among the most difficult cancers to treat. Despite the aggressive standard of care, including surgical removal followed by radiotherapy with concomitant and adjuvant chemotherapy, the often sudden onset, diffuse infiltrating nature and highly malignant features of the lesion result in a median overall survival of < 15 months. Currently employed standard- of-care therapy for glioblastoma is nonspecific, leading to premature withdrawal of treatment due to off-target toxicity. Rindopepimut is a peptide-based vaccine that elicits a potent humoral and cellular immune response specifically against cells expressing EGFRvIII, a rearranged, cell-surface tyrosine kinase receptor present exclusively in glioblastoma and other common neoplasms. Several phase I and phase II clinical trials have demonstrated that vaccination with Rindopepimut is safe, well tolerated and produces a highly potent immune response that effectively eradicates EGFRvIII-expressing tumor cells, leading to a 73% increase in survival among patients with newly diagnosed glioblastoma. Furthermore, temozolomide-induced lymphopenia enhances the Rindopepimut-induced immune response against EGFRvIII, allowing for enhanced vaccination responses in the context of standard-of-care chemotherapy. Rindopepimut is currently undergoing evaluation in a phase III international trial for newly diagnosed glioblastoma and is under clinical investigation for recurrent glioblastoma and pediatric brain stem gliomas.
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react a phase ii study of Rindopepimut cdx 110 plus bevacizumab bv in relapsed glioblastoma gb
Journal of Clinical Oncology, 2012Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Ronald G Steis, Erin M Dunbar, Nitin B Chandramouli, Olivier Rixe, Jennifer Green, Thomas A Davis, John H SampsonAbstract:TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). The investigational vaccine Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally (500ug with 150ug GM-CSF as an adjuvant). Remarkably consistent and promising results across 3 phase II studies in newly diagnosed, resected EGFRvIII+ GB (Lai 2011) represent a statistically significant improvement over a historical control cohort matched for major eligibility criteria (median overall survival [OS] = 24.4 - 24.6 vs. 15.2 months from diagnosis [m] and median progression-free survival [PFS] = 12.3 - 15.3 vs. 6.4 m). ACT IV, a phase III trial in this population, is ongoing. The immunosuppressive influence of residual/advanced GB presents a challenge to activation of efficacious antitumor immune responses. Anecdotal evidence (compassionate us...
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react a phase ii study of Rindopepimut cdx 110 plus bevacizumab bv in relapsed glioblastoma gb
Journal of Clinical Oncology, 2012Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Ronald G Steis, Erin M Dunbar, Olivier Rixe, Jennifer Green, Thomas A Davis, Nitin Chandramouli, John H SampsonAbstract:TPS2103 Background: EGFRvIII is a constitutively active tumorigenic deletion mutation of EGFR. It is expressed in ~30% of primary GB where it is linked to poor long-term survival (Pelloski 2007). T...
Annick Desjardins - One of the best experts on this subject based on the ideXlab platform.
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Rindopepimut with bevacizumab for patients with relapsed egfrviii expressing glioblastoma react results of a double blind randomized phase ii trial
Clinical Cancer Research, 2020Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Donald M Orourke, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S AshbyAbstract:Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of Rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naive patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive Rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 Rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for Rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the Rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of Rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
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imct 08react long term survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:BACKGROUND: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of an EGFRvIII-specific peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety. METHODS: In the Phase II “ReACT” study, 73 bevacizumab (BV)-naive pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary; target α = 0.2 by 1-sided chi-square test), objective response rate (ORR), PFS, OS and safety. RESULTS: Primary Rindopepimut toxicity is Grade 1-2 injection site reaction. For Rindopepimut + BV vs. KLH + BV (per centralized review; RANO criteria): PFS6 = 28% (10/36) vs. 16% (6/37) (p = 0.116); ORR = 30% (9/30) vs. 18% (6/34). Cessation of steroids > 2 months: 44% (8/18) vs 21% (4/19), >6 months: 33% (6/18) vs. 0. Median (95% CI) OS = 11.6 (10.0, 16.2) vs. 9.3 (7.1, 11.3) months (HR = 0.57 [0.33, 0.98], p = 0.039). 9 vs 6 pts remain in follow-up; 6 vs. 2 are progression-free. OS analyses adjusted for various prognostic factors consistently favor Rindopepimut. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Antibodies, predominantly IgG1 isotype, mediate killing of EGFRvIII+ tumor cells through ADCC and CDCC in vitro. Within the Rindopepimut arm, peak titer (≥1:12,800 at any time) and rapid titer generation (≥1:12,800 by Day 57) were associated with prolonged OS (HR = 0.16, p = <0.0001 and HR = 0.59, p = 0.182, respectively). Evaluation of humoral response quality, HLA typing vs. outcome, and survival follow-up continue. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. CONCLUSIONS: Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.
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107 react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neurosurgery, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:Author(s): Reardon, DA; Schuster, JM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Desjardins, A; Ashby, LS; Duic, JP; Mrugala, MM; Werner, A; Hawthorne, T; He, Y; Green, J; Yellin, MJ; Turner, CD; Davis, TA; Sampson, JH | Abstract: INTRODUCTION: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with granulocyte macrophage colony-stimulating factor. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS), and safety profile. Compassionate-use experience suggests that Rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV). METHODS: In the Phase II "ReACT" study, BV-naive patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). END POINTS: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety. RESULTS: Accrual is complete (n = 72); study follow-up continues (n = 30). Primary Rindopepimut toxicity is grade 1 to 2 injection site reaction. For Rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side χ test); ORR = 24% (7/29) vs 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; P = .0208), with 8 vs 4 patients progression-free. OS analyses favor Rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the Rindopepimut arm, and was most frequent in patients with KPS ≥ 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response. CONCLUSION: These near-final data show that Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV in patients with relapsed GB.
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react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Journal of Clinical Oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:2009 Background: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists ...
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it 30react a phase ii study of Rindopepimut vaccine cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2014Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J Duic, Lynn AneiroAbstract:BACKGROUND: EGFRvIII, a constitutively active tumorigenic EGFR deletion mutation, is linked to poor long-term survival. The investigational vaccine Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of Rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. Bevacizumab (BV), an agent with activity in glioblastoma, may augment EGFRvIII-specific immune response and antitumor activity through inhibition of VEGF and its immunosuppressive properties. METHODS: “ReACT” is a Phase II study of Rindopepimut plus BV in patients with 1st or 2nd relapse of EGFRvIII+ glioblastoma. BV-naive pts (Group 1; n = 70) are randomized 1:1 to BV plus double-blinded injection of either Rindopepimut or control (KLH). BV-refractory patients (progression within 2 months of BV; Group 2/2C, n = 98) receive BV plus open-label Rindopepimut. RESULTS: 234/700 (33%) screened patients are EGFRvIII+. 115 patients (Group 1 = 72, Group 2/2C = 43) are enrolled. Primary toxicity is Grade 1-2 injection site reaction. In group 1, for Rindopepimut + BV vs. KLH + BV, objective response rate (ORR; investigator-assessed, RANO criteria) is 23% (6/26) vs 12% (3/25) [35% vs. 20% including responses observed at a single time point (“unconfirmed”)]. In Group 2/2C (evaluable n = 30), one unconfirmed PR and one sustained PR (patient continues treatment at 15 months) occurred. Two additional patients had pre-study progression >2 months after BV; one maintained a CR for 11.1 months (peak anti-EGFRvIII titer = 1:3,276,800), while the second experienced an unconfirmed CR. Median peak Rindopepimut-induced anti-EGFRvIII humoral response is 1:25,600 [range <1:100-1:6,553,600]). Rapid titer generation was associated with prolonged OS (Group 2: p = 0.01). CONCLUSIONS: Rindopepimut + BV has induced potent EGFRvIII-specific immune response and tumor regression in immunosuppressed recurrent glioblastoma patients naive or refractory to BV. Full response, PFS and OS data are expected to further define the potential clinical benefit of the combination in relapsed glioblastoma.
Lynn S Ashby - One of the best experts on this subject based on the ideXlab platform.
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Rindopepimut with bevacizumab for patients with relapsed egfrviii expressing glioblastoma react results of a double blind randomized phase ii trial
Clinical Cancer Research, 2020Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Donald M Orourke, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S AshbyAbstract:Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of Rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naive patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive Rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 Rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for Rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the Rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of Rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
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imct 08react long term survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:BACKGROUND: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of an EGFRvIII-specific peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety. METHODS: In the Phase II “ReACT” study, 73 bevacizumab (BV)-naive pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary; target α = 0.2 by 1-sided chi-square test), objective response rate (ORR), PFS, OS and safety. RESULTS: Primary Rindopepimut toxicity is Grade 1-2 injection site reaction. For Rindopepimut + BV vs. KLH + BV (per centralized review; RANO criteria): PFS6 = 28% (10/36) vs. 16% (6/37) (p = 0.116); ORR = 30% (9/30) vs. 18% (6/34). Cessation of steroids > 2 months: 44% (8/18) vs 21% (4/19), >6 months: 33% (6/18) vs. 0. Median (95% CI) OS = 11.6 (10.0, 16.2) vs. 9.3 (7.1, 11.3) months (HR = 0.57 [0.33, 0.98], p = 0.039). 9 vs 6 pts remain in follow-up; 6 vs. 2 are progression-free. OS analyses adjusted for various prognostic factors consistently favor Rindopepimut. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Antibodies, predominantly IgG1 isotype, mediate killing of EGFRvIII+ tumor cells through ADCC and CDCC in vitro. Within the Rindopepimut arm, peak titer (≥1:12,800 at any time) and rapid titer generation (≥1:12,800 by Day 57) were associated with prolonged OS (HR = 0.16, p = <0.0001 and HR = 0.59, p = 0.182, respectively). Evaluation of humoral response quality, HLA typing vs. outcome, and survival follow-up continue. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. CONCLUSIONS: Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.
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107 react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neurosurgery, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:Author(s): Reardon, DA; Schuster, JM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Desjardins, A; Ashby, LS; Duic, JP; Mrugala, MM; Werner, A; Hawthorne, T; He, Y; Green, J; Yellin, MJ; Turner, CD; Davis, TA; Sampson, JH | Abstract: INTRODUCTION: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with granulocyte macrophage colony-stimulating factor. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS), and safety profile. Compassionate-use experience suggests that Rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV). METHODS: In the Phase II "ReACT" study, BV-naive patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). END POINTS: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety. RESULTS: Accrual is complete (n = 72); study follow-up continues (n = 30). Primary Rindopepimut toxicity is grade 1 to 2 injection site reaction. For Rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side χ test); ORR = 24% (7/29) vs 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; P = .0208), with 8 vs 4 patients progression-free. OS analyses favor Rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the Rindopepimut arm, and was most frequent in patients with KPS ≥ 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response. CONCLUSION: These near-final data show that Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV in patients with relapsed GB.
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react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Journal of Clinical Oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:2009 Background: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists ...
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it 30react a phase ii study of Rindopepimut vaccine cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2014Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J Duic, Lynn AneiroAbstract:BACKGROUND: EGFRvIII, a constitutively active tumorigenic EGFR deletion mutation, is linked to poor long-term survival. The investigational vaccine Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of Rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. Bevacizumab (BV), an agent with activity in glioblastoma, may augment EGFRvIII-specific immune response and antitumor activity through inhibition of VEGF and its immunosuppressive properties. METHODS: “ReACT” is a Phase II study of Rindopepimut plus BV in patients with 1st or 2nd relapse of EGFRvIII+ glioblastoma. BV-naive pts (Group 1; n = 70) are randomized 1:1 to BV plus double-blinded injection of either Rindopepimut or control (KLH). BV-refractory patients (progression within 2 months of BV; Group 2/2C, n = 98) receive BV plus open-label Rindopepimut. RESULTS: 234/700 (33%) screened patients are EGFRvIII+. 115 patients (Group 1 = 72, Group 2/2C = 43) are enrolled. Primary toxicity is Grade 1-2 injection site reaction. In group 1, for Rindopepimut + BV vs. KLH + BV, objective response rate (ORR; investigator-assessed, RANO criteria) is 23% (6/26) vs 12% (3/25) [35% vs. 20% including responses observed at a single time point (“unconfirmed”)]. In Group 2/2C (evaluable n = 30), one unconfirmed PR and one sustained PR (patient continues treatment at 15 months) occurred. Two additional patients had pre-study progression >2 months after BV; one maintained a CR for 11.1 months (peak anti-EGFRvIII titer = 1:3,276,800), while the second experienced an unconfirmed CR. Median peak Rindopepimut-induced anti-EGFRvIII humoral response is 1:25,600 [range <1:100-1:6,553,600]). Rapid titer generation was associated with prolonged OS (Group 2: p = 0.01). CONCLUSIONS: Rindopepimut + BV has induced potent EGFRvIII-specific immune response and tumor regression in immunosuppressed recurrent glioblastoma patients naive or refractory to BV. Full response, PFS and OS data are expected to further define the potential clinical benefit of the combination in relapsed glioblastoma.
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Rindopepimut with bevacizumab for patients with relapsed egfrviii expressing glioblastoma react results of a double blind randomized phase ii trial
Clinical Cancer Research, 2020Co-Authors: David A Reardon, Annick Desjardins, James J Vredenburgh, Donald M Orourke, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S AshbyAbstract:Purpose: Rindopepimut is a vaccine targeting the tumor-specific EGF driver mutation, EGFRvIII. The ReACT study investigated whether the addition of Rindopepimut to standard bevacizumab improved outcome for patients with relapsed, EGFRvIII-positive glioblastoma. Patients and Methods: In this double-blind, randomized, phase II study (NCT01498328) conducted at 26 hospitals in the United States, bevacizumab-naive patients with recurrent EGFRvIII-positive glioblastoma were randomized to receive Rindopepimut or a control injection of keyhole limpet hemocyanin, each concurrent with bevacizumab. The primary endpoint was 6-month progression-free survival (PFS6) by central review with a one-sided significance of 0.2. Results: Between May 2012 and 2014, 73 patients were randomized (36 Rindopepimut, 37 control). Rindopepimut toxicity included transient, low-grade local reactions. As primary endpoint, PFS6 was 28% (10/36) for Rindopepimut compared with 16% (6/37) for control (P = 0.12, one-sided). Secondary and exploratory endpoints also favored the Rindopepimut group including a statistically significant survival advantage [HR, 0.53; 95% confidence interval (CI), 0.32–0.88; two-sided log-rank P = 0.01], a higher ORR [30% (9/30) vs. 18% (6/34; P = 0.38)], median duration of response [7.8 months (95% CI, 3.5–22.2) vs. 5.6 (95% CI, 3.7–7.4)], and ability to discontinue steroids for ≥6 months [33% (6/18) vs. 0% (0/19)]. Eighty percent of Rindopepimut-treated patients achieved robust anti-EGFRvIII titers (≥1:12,800), which were associated with prolonged survival (HR = 0.17; 95% CI, 0.07–0.45; P Conclusions: Our randomized trial supports the potential for targeted immunotherapy among patients with GBM, but the therapeutic benefit requires validation due to the small sample size and potential heterogeneity of bevacizumab response among recurrent patients with GBM.
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imct 08react long term survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neuro-oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:BACKGROUND: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of an EGFRvIII-specific peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety. METHODS: In the Phase II “ReACT” study, 73 bevacizumab (BV)-naive pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary; target α = 0.2 by 1-sided chi-square test), objective response rate (ORR), PFS, OS and safety. RESULTS: Primary Rindopepimut toxicity is Grade 1-2 injection site reaction. For Rindopepimut + BV vs. KLH + BV (per centralized review; RANO criteria): PFS6 = 28% (10/36) vs. 16% (6/37) (p = 0.116); ORR = 30% (9/30) vs. 18% (6/34). Cessation of steroids > 2 months: 44% (8/18) vs 21% (4/19), >6 months: 33% (6/18) vs. 0. Median (95% CI) OS = 11.6 (10.0, 16.2) vs. 9.3 (7.1, 11.3) months (HR = 0.57 [0.33, 0.98], p = 0.039). 9 vs 6 pts remain in follow-up; 6 vs. 2 are progression-free. OS analyses adjusted for various prognostic factors consistently favor Rindopepimut. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Antibodies, predominantly IgG1 isotype, mediate killing of EGFRvIII+ tumor cells through ADCC and CDCC in vitro. Within the Rindopepimut arm, peak titer (≥1:12,800 at any time) and rapid titer generation (≥1:12,800 by Day 57) were associated with prolonged OS (HR = 0.16, p = <0.0001 and HR = 0.59, p = 0.182, respectively). Evaluation of humoral response quality, HLA typing vs. outcome, and survival follow-up continue. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. CONCLUSIONS: Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.
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107 react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Neurosurgery, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:Author(s): Reardon, DA; Schuster, JM; Tran, DD; Fink, KL; Nabors, LB; Li, G; Bota, DA; Lukas, RV; Desjardins, A; Ashby, LS; Duic, JP; Mrugala, MM; Werner, A; Hawthorne, T; He, Y; Green, J; Yellin, MJ; Turner, CD; Davis, TA; Sampson, JH | Abstract: INTRODUCTION: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with granulocyte macrophage colony-stimulating factor. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS), and safety profile. Compassionate-use experience suggests that Rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV). METHODS: In the Phase II "ReACT" study, BV-naive patients in 1st or 2nd relapse with EGFRvIII+ GB were randomly assigned 1:1 to BV plus double-blinded injection of Rindopepimut or control (KLH). END POINTS: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS, and safety. RESULTS: Accrual is complete (n = 72); study follow-up continues (n = 30). Primary Rindopepimut toxicity is grade 1 to 2 injection site reaction. For Rindopepimut + BV vs KLH + BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs 11% (4/35) (P = .048, 1-side χ test); ORR = 24% (7/29) vs 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; P = .0208), with 8 vs 4 patients progression-free. OS analyses favor Rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12800-1:6553600) in 80% of patients. Rapid titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; P = .128) within the Rindopepimut arm, and was most frequent in patients with KPS ≥ 90 (odds ratio = 9.75; P = .007). Evaluation of humoral response quality and HLA typing vs outcome are underway. In an additional cohort of BV-exposed patients (n = 53), four patients experienced objective tumor response. CONCLUSION: These near-final data show that Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV in patients with relapsed GB.
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react overall survival from a randomized phase ii study of Rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
Journal of Clinical Oncology, 2015Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J DuicAbstract:2009 Background: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine Rindopepimut consists ...
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the evolution of the egfrviii Rindopepimut immunotherapy for glioblastoma multiforme patients
Human Vaccines & Immunotherapeutics, 2014Co-Authors: Michelle Paff, Daniela Alexandruabrams, Frank P K Hsu, Daniela A BotaAbstract:Glioblastoma Multiforme (GBM) is the most common type of brain tumor and it is uniformly fatal. The community standard of treatment for this disease is gross or subtotal resection of the tumor, followed by radiation and temozolomide. At recurrence bevacizumab can be added for increased progression free survival. Many challenges are encountered while trying to devise new drugs to treat GBM, such as the presence of the blood brain barrier which is impermeable to most drugs. Therefore in the past few years attention was turned to immunological means for the treatment of this devastating disease. EGFRvIII targeting has proven a good way to attack glioblastoma cells by using the immune system. Although in still in development, this approach holds the promise as a great first step toward immune-tailored drugs for the treatment of brain cancers.
