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The combination of atezolizumab plus cabozantinib demonstrated promising antitumor activity with a tolerable safety profile among patients with previously untreated clear cell renal cell carcinoma (ccRCC), according to results of a phase 1b trial presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
“Cabozantinib promotes an immune-permissive environment that may enhance response to immune checkpoint inhibitors,” Sumanta Pal, MD, of the City of Hope Comprehensive Cancer Center in Duarte, California, and presenter of the study, said.
The phase 1b COSMIC-021 trial is evaluating the atezolizumab plus cabozantinib for multiple different advanced solid tumor types. This analysis included 70 patients with previously untreated ccRCC from the dose-escalation and expansion phases. Patients received 40 mg or 60 mg of cabozantinib and all patients received 1200 mg of atezolizumab every 3 weeks. The primary endpoint was objective response rate (ORR), and the secondary endpoint was safety.
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At baseline, the median age was 64 and 76% were male. In the 60-mg cabozantinib group, 39% of patients had favorable disease and 61% had intermediate/poor risk diseases. In the 40 mg cabozantinib group, 21% and 79% of patients had favorable risk disease or intermediate/poor risk disease, respectively. A sarcomatoid component was present in 26% and 6% of patients, respectively.
The ORR was similar between dose levels, at 53% with 40 mg and 58% with 60 mg of cabozantinib. The disease control rate was high in both groups, at 94% with 40 mg and 92% with 60 mg of cabozantinib. The duration of response was not estimable with 40 mg and was 15.4 months with 60 mg of cabozantinib.
“Many patients with a sarcomatoid component had a large target reduction,” Dr Pal said.
Progression-free survival was 19.5 months with 40 mg of cabozantinib and 15.1 months with 60 mg of cabozantinib.
Better best overall response was associated with PD-L1 positivity (P =.001), defined as ≥1% of tumor-infiltrating immune cells, but some patients with low or no PD-L1–positive tumors experienced a response. High CD8-positive T-cells (≥20%) was associated with greater rates of complete or partial response (P =.05). This association was also apparent when PD-L1 positivity and high CD8-positive T-cells were combined.
Patients with a tumor-infiltrating immune phenotype were also more likely to experience a response than patients with a myeloid dominant or immune low phenotype (P =.02).
The most common grade 3-4 treatment-related adverse events (TRAEs) were diarrhea, hypertension, alanine transferase elevation, and hypophosphatemia. Treatment discontinuations due to TRAEs occurred among 24% and 19% of patients in the 40-mg and 60-mg cabozantinib groups, respectively, though the 60-mg group had approximately 10 months longer follow-up. There were no dose-limiting toxicities during the dose-expansion phase and there were no grade 5 events.
Immune-related AEs occurred among a mean of 26% of patients, with 19% of grade 3-4 severity.
Dr Pal concluded that “the combination of cabozantinib and atezolizumab demonstrated encouraging clinical activity in previously untreated patients with advanced ccRCC.” He added that the phase 3 CONTACT-03 trial among patients with previously treated advanced RCC is ongoing.
Disclosures: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.
Read more of Cancer Therapy Advisor‘s coverage of the ESMO Virtual Congress 2020 by visiting the conference page.
Reference
Pal S, Tsao C-K, Suarez C, et al. Cabozantinib (C) in combination with atezolizumab (A) as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): results from the COSMIC-021 study. Presented at: European Society for Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. Abstract 702O.
