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The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.
Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.
Phase 1b
The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).
The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.
The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.
The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
Phase 2
The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).
Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.
After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.
The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
Safety
In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).
The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).
Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.
“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”
This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.
SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.
The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.
Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.
Phase 1b
The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).
The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.
The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.
The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
Phase 2
The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).
Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.
After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.
The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
Safety
In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).
The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).
Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.
“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”
This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.
SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.
The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.
Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.
Phase 1b
The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).
The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.
The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.
The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
Phase 2
The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).
Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.
After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.
The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
Safety
In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).
The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).
Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.
“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”
This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.
SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.
FROM THE JOURNAL OF CLINICAL ONCOLOGY