The Experts below are selected from a list of 36 Experts worldwide ranked by ideXlab platform
Jeffrey S Weber - One of the best experts on this subject based on the ideXlab platform.
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safety and tumor responses with Lambrolizumab anti pd 1 in melanoma
2013Co-Authors: Omid Hamid, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Wenjen Hwu, Peter Hersey, Richard W Joseph, Jeffrey S WeberAbstract:A b s t r ac t Background The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti–PD-1 antibody Lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. Methods We administered Lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. Results A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. Conclusions In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with Lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. (Funded by Merck Sharp and Dohme; ClinicalTrials.gov number, NCT01295827.)
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clinical efficacy and safety of Lambrolizumab mk 3475 anti pd 1 monoclonal antibody in patients with advanced melanoma
2013Co-Authors: Antoni Ribas, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Amita Patnaik, Wenjen Hwu, Jeffrey S Weber, Anthony M JoshuaAbstract:9009Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1....
Talha Khan Burki - One of the best experts on this subject based on the ideXlab platform.
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Lambrolizumab induces advanced melanoma regression
2013Co-Authors: Talha Khan BurkiAbstract:Formerly known as MK-3475, Lambrolizumab is an antibody that targets PD-1, and a phase 1 clinical trial has indicated that it could be a highly eff ective therapy for advanced melanoma. The researchers prescribed Lambrolizumab to 135 patients with advanced melanoma. 48 of these patients had previously been treated with ipilimumab. The overall response rate was 38% (95% CI 25–44); those in the cohort with the highest dose of Lambrolizumab had a response rate of 52% (95% CI 38–66). Moreover, the responses were durable. 81% of patients who had a response continued to receive treatment at the time of analysis. “Treatment with Lambrolizumab resulted in a high rate of sustained tumour regression with mainly grade 1 or 2 toxic eff ects”, the authors concluded. Interestingly, the response rate was roughly the same regardless of whether patients’ had previously received ipilimumab. “It is related to the idea that all immunotherapies are diff erent; whether you’ve had previous therapy or not, you still have a high chance of responding”, explains coauthor Omid Hamid (Angeles Clinic and Research Institute, Los Angeles, California, USA). The future will bring trials of the drug in combination, while a randomised trial between Lambrolizumab and chemotherapy is ongoing. “Clearly the goal of this drug is to fi nd its way towards approval for metastatic melanoma and also to look at it in terms of other solid tumours including breast cancer and lung cancer”, Hamid told The Lancet Oncology. “All the PD-1 and PDL-1 inhibitors are paradigm shifters for therapy”, adds Hamid. “They don’t just shift the paradigm for melanoma; they have the ability to shift it for all solid tumours”. In which case, a robust biomarker would be extremely useful. “We’d like to know which patients should receive PD-1 treatment, and we still don’t really know that”, affi rmed Lynn Schuchter (University of Pennsylvania, USA). Schuchter believes that Lambrolizumab has enormous potential. “To see this kind of activity with a lack of signifi cant autoimmune toxicity is certainly encouraging”. She points out that it has been diffi cult to partner molecularly targeted therapies, BRAF inhibitors, with ipilimumab. “Maybe with this more favourable safety profi le, we will be able to partner the PD-1 antibodies with the BRAF inhibitors”, she told The Lancet Oncology.
Christopher P Leamon - One of the best experts on this subject based on the ideXlab platform.
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abstract 262 combination therapy of folate targeted chemotherapeutics with anti pd 1 antibody against folate receptor positive tumors in immunocompetent murine models
2016Co-Authors: Yingjuan June Lu, Leroy W Wheeler, Vicky A Cross, Elaine Westrick, Alex M Lloyd, Christopher P LeamonAbstract:The PD-1/PD-L1 (programmed cell death protein 1; programmed death-ligand 1) pathway plays a key role in immunological tolerance and autoimmunity. PD-1 is primarily expressed on activated T and B cells while its receptor, PD-L1, is expressed in a variety of cell types including resting lymphocytes, DCs, and macrophages. Recently, multiple human solid tumor types (melanoma, NSCLC, RCC, ovarian, and colorectal cancer) have been found to overexpress PD-L1 within its tumor microenvironment. More importantly, PD-1/PD-L1 blocking agents (pembrolizumab, nivolumab, Lambrolizumab, MPDL3280A) have been found active as a single agent or in combination with chemotherapy and some have produced durable clinical responses. On the other hand, human epithelial tumors are also known to overexpress the high-affinity folate receptor (FR)-alpha that is capable of bringing folate-linked drugs into the cell cytosol via endocytosis. Using flow cytometry, we assessed PD-L1 expression in various FR-positive syngeneic mouse tumor models (M109, Renca, L1210A, 4T1-Cl2, ID8-Cl15). PD-L1 expression was found to vary significantly among different tumor types and could be found not only on CD45- malignant cells but also on tumor stromal cells such as F4/80+CD11b+ tumor-associated macrophages. Using a rat anti-mouse PD-1 antibody (clone RMP1-14), we studied in-vivo efficacy of a folate-targeted chemotherapy in combination with PD-1/PD-L1 blockage in PD-L1-expressing tumor models. In syngeneic models with high PD-L1 expression and tumor-infiltrating lymphocytes, a synergistic and curable anti-tumor effect was observed and the animals developed tumor-protective immunity against rechallenge. Thus, our preliminary results suggest that folate-targeted chemotherapeutics may also be enhanced by PD-1/PD-L1 blockage by means of overcoming tumor-mediated immune suppression Citation Format: Yingjuan June Lu, Leroy W. Wheeler, Vicky Cross, Elaine Westrick, Alex Lloyd, Christopher P. Leamon. Combination therapy of folate-targeted chemotherapeutics with anti-PD-1 antibody against folate receptor-positive tumors in immunocompetent murine models. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 262.
Adil Daud - One of the best experts on this subject based on the ideXlab platform.
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safety and tumor responses with Lambrolizumab anti pd 1 in melanoma
2013Co-Authors: Omid Hamid, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Wenjen Hwu, Peter Hersey, Richard W Joseph, Jeffrey S WeberAbstract:A b s t r ac t Background The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti–PD-1 antibody Lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. Methods We administered Lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. Results A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. Conclusions In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with Lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. (Funded by Merck Sharp and Dohme; ClinicalTrials.gov number, NCT01295827.)
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clinical efficacy and safety of Lambrolizumab mk 3475 anti pd 1 monoclonal antibody in patients with advanced melanoma
2013Co-Authors: Antoni Ribas, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Amita Patnaik, Wenjen Hwu, Jeffrey S Weber, Anthony M JoshuaAbstract:9009Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1....
Caroline Robert - One of the best experts on this subject based on the ideXlab platform.
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safety and tumor responses with Lambrolizumab anti pd 1 in melanoma
2013Co-Authors: Omid Hamid, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Wenjen Hwu, Peter Hersey, Richard W Joseph, Jeffrey S WeberAbstract:A b s t r ac t Background The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti–PD-1 antibody Lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. Methods We administered Lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. Results A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. Conclusions In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with Lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. (Funded by Merck Sharp and Dohme; ClinicalTrials.gov number, NCT01295827.)
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clinical efficacy and safety of Lambrolizumab mk 3475 anti pd 1 monoclonal antibody in patients with advanced melanoma
2013Co-Authors: Antoni Ribas, Caroline Robert, Adil Daud, Stephen F Hodi, Jedd D Wolchok, Richard F Kefford, Amita Patnaik, Wenjen Hwu, Jeffrey S Weber, Anthony M JoshuaAbstract:9009Background: Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1....
