Results from COSMIC-021 Trial Announced: Cabozanitinib in Combination with Atezolizumab with Multiple Advanced Solid Tumor Types

San Francisco, California ( Exelixis, Inc. announced phase 1b clinical trial results for the combination of cabozantinib (CABOMETYX®) and atezolizumab (TECENTRIQ®) in patients with locally advanced or metastatic solid tumors. The data from three expansion cohorts of the COSMIC-021 trial will be presented during the 2020 American Society of Clinical Oncology Virtual Scientific Program (ASCO 20). Results from the non-small cell lung cancer (NSCLC) and the metastatic castration resistant prostate cancer (CRPC) cohorts will be presented as posters, and results from the urothelial carcinoma (UC) cohort will be presented as a poster discussion; all three presentations will be available on demand for ASCO20 registrants beginning Friday, May 29 at 8:00 a.m. ET.

NSCLC Expansion Cohort (abstract 9610): Initial results from the NSCLC expansion cohort (cohort 7) will be presented by Joel Neal, M.D., Ph.D., Associate Professor of Medicine – Oncology at the Stanford University School of Medicine, one of the lead trial investigators. The analysis included 30 patients who had received prior therapy with immune checkpoint inhibitors, and 87% of patients had received prior chemotherapy. Fifty percent of patients received the cabozantinib and atezolizumab combination as their second line of therapy and 50% as their third line of therapy. At the time of enrollment in the study, the best response to prior immune checkpoint inhibitor therapy was a partial response in 3 (10%) patients, stable disease in 7 (23%) patients, progressive disease in 14 (47%) patients and unknown in 5 (17%) patients.

At a median follow-up of 12.1 months, the investigator-assessed confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, the trial’s primary endpoint, was 27%, and the disease control rate was 83%. Median progression-free survival (PFS) was 4.2 months (95% confidence interval [CI] 2.7–7 months) with 22 events (73%), and median duration of response for all responding patients was 5.7 months.

“Cabozantinib, in combination with immune checkpoint inhibitors, has now demonstrated promise in multiple difficult to treat tumor types,” said Dr. Sumanta Pal, Clinical Professor, City of Hope, the principal investigator for the COSMIC-021 study.

“The findings from the three COSMIC-021 cohorts presented at ASCO20 add to the growing body of evidence of potential synergistic effects with cabozantinib and immune checkpoint inhibitors. We are particularly encouraged by the new data emerging from the NSCLC cohort which showed a 27% confirmed overall response rate, including three patients with primary refractory disease to checkpoint inhibition. Further evaluation of cabozantinib and atezolizumab in patients with advanced tumor types, including immune checkpoint inhibitor-pretreated NSCLC, and forms of prostate and urothelial cancers, is warranted.”
The most common treatment-related adverse events (AEs) were diarrhea (53%), fatigue (37%), nausea (30%), decreased appetite (23%), palmar-plantar erythrodysesthesia (20%) and vomiting (20%). One patient experienced grade 5 pneumonitis that was related to atezolizumab, and one patient (3%) discontinued due to treatment-related AEs not associated with disease progression.

“We are encouraged by these promising findings in patients with non-small cell lung cancer who had been previously treated with immune checkpoint inhibitor therapy, along with other COSMIC-021 results presented at ASCO20,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The efficacy data and favorable safety profiles seen in the three cohorts suggest the combination of cabozantinib and atezolizumab offers promise for patients with advanced, difficult-to-treat tumor types. These findings and additional data from these cohorts will inform the design of future studies, including planned phase 3 pivotal trials for the combination of cabozantinib and atezolizumab in advanced or metastatic NSCLC and CRPC.”

UC Expansion Cohort (abstract 5013): Initial results from the UC expansion cohort (cohort 2) will be presented by Dr. Pal. The analysis included 30 patients who had been previously treated with platinum-containing chemotherapy, with a median follow-up of 19.7 months. The investigator-assessed ORR per RECIST v. 1.1 was 27%, with two complete responses; disease control rate was 63%. Median duration of response was not yet reached, and the longest ongoing response was 15.6 months. Median PFS was 5.4 months. Preliminary data did not suggest an association between PD-L1 expression and tumor response.

The most common treatment-related AEs were asthenia (37%), diarrhea (27%), decreased appetite (23%), increased transaminases (23%), and mucosal inflammation (20%). No discontinuations due to treatment related AEs occurred. 

CRPC Expansion Cohort (abstract 5564): An interim analysis from the metastatic CRPC expansion cohort (cohort 6) was previously presented at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium and was now updated with additional biomarker results that will be presented by Neeraj Agarwal, M.D., Professor, Huntsman Cancer Center, University of Utah, and an investigator of the trial. This analysis of 44 patients who had been previously treated with enzalutamide and/or abiraterone found an ORR per RECIST v. 1.1 of 32% and a disease control rate of 80% at a median follow up of 15.8 months. Preliminary data from the analysis did not suggest an association between PD-L1 expression and antitumor activity, suggesting patients with or without PD-L1 may respond to treatment with the combination of cabozantinib plus atezolizumab. Comparison of baseline and circulating immune cell counts after 21 days showed a total increase in circulating T cells (CTLs) and a decrease in immunosuppressive cells. Subpopulations of CTLs also increased with the largest accumulation observed for prolonged activated CTLs.

Additional safety and efficacy findings from this analysis were previously presented at the 2020 American Society of Clinical Oncology’s Genitourinary Cancers Symposium.

Based on regulatory feedback from the U.S. Food & Drug Administration (FDA), and if supported by the clinical data, Exelixis intends to file with the FDA for accelerated approval in a metastatic CRPC indication as early as 2021.

Source: "Exelixis Announces Results From COSMIC-021 Trial Of Cabozantinib In Combination With Atezolizumab In Multiple Advanced Solid Tumor Types | Exelixis, Inc.". 2020. Exelixis, Inc.

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