Exelixis Announces Results from Two Renal Cell Carcinoma Cohorts of the COSMIC-021 Trial of Cabozantinib in Combination with Atezolizumab

– Cabozantinib in combination with atezolizumab demonstrated promising preliminary efficacy and a favorable safety profile in cohorts of patients with clear cell and non-clear cell renal cell carcinoma

– Data presented during the European Society for Medical Oncology Virtual Congress 2020

San Francisco, CA (UroToday.com) -- Exelixis, Inc. announced positive phase 1b clinical trial results for the combination of cabozantinib (CABOMETYX®) and atezolizumab (TECENTRIQ®) in patients with locally advanced or metastatic solid tumors. Data from two expansion cohorts of the COSMIC-021 trial were presented during the European Society for Medical Oncology (ESMO) Virtual Congress 2020. Results from the clear cell renal cell carcinoma (RCC) cohort are being presented in the GU Proffered Paper Session on September 21, 2020, and results from the non-clear cell RCC cohort were presented as a poster available on-demand for registrants beginning September 17, 2020, at 9:00 a.m. CEST.

“Given the broad experience with cabozantinib as monotherapy for advanced kidney cancer, it’s very exciting to see the growing body of clinical evidence that demonstrates encouraging tolerability and clinical activity when combining cabozantinib with atezolizumab in this disease,” said Dr. Sumanta Pal Clinical Professor, City of Hope, the principal investigator for the COSMIC-021 study. “We are especially encouraged to see a durable objective response in more than 50% of patients with previously untreated clear cell RCC, paired with an acceptable safety profile at both cabozantinib dose levels evaluated in combination with atezolizumab. We look forward to learning more about the potential of this combination regimen to improve outcomes for patients with advanced kidney cancer from the ongoing phase 3 CONTACT-03 trial.”
Clear Cell RCC Expansion Cohort (abstract 702O):

Initial results from the clear cell RCC expansion cohort (cohort 1) are being presented by Dr. Pal. The analysis included 70 RCC patients with clear cell histology who had not received prior systemic therapy. Patients received atezolizumab in combination with either a 40 mg or 60 mg daily dose of cabozantinib.

At a median follow-up of 25.8 months for the cabozantinib 40 mg dose group, the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, the trial’s primary endpoint for the expansion cohorts, was 53%, with one complete response; disease control rate was 94%. Median progression-free survival (PFS) was 19.5 months (95% confidence interval [CI] 11.0–NR) with 17 events observed among 34 patients. Median duration of response was not yet reached.

At a median follow-up of 15.3 months for the cabozantinib 60 mg dose group, ORR per RECIST v. 1.1 was 58%, with four complete responses; disease control rate was 92%. Median PFS was 15.1 months (95% CI 8.2–22.3) with 19 events observed among 36 patients. Median duration of response for all responding patients was 15.4 months.

For both dose groups combined, positive PD-L1 status at baseline and higher levels of CD8+ T cells each showed a significant positive association with overall response.

In the 40 mg dose group, treatment-related grade 3/4 adverse events (AEs) occurring in ≥5% of patients were diarrhea (9%), fatigue (6%), hypertension (24%), and hypophosphatemia (15%); the discontinuation rate for either cabozantinib or atezolizumab due to treatment-related AEs was 24%, and 15% discontinued both study treatments due to treatment-related AEs. In the 60 mg dose group, treatment-related grade 3/4 were diarrhea (19%), fatigue (6%), hypertension (14%), alanine aminotransferase (ALT) increased (14%), aspartate aminotransferase (AST) increased (6%), lipase increased (8%) and mucosal inflammation (6%); the discontinuation rate for either study treatment due to treatment-related AEs was 19%, and 6% discontinued both study treatments due to treatment-related AEs.

Non-Clear Cell RCC Expansion Cohort (abstract 709P):

Initial results from the non-clear cell expansion cohort (cohort 10) were presented by Dr. Bradley A. McGregor, Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. The analysis included 30 patients with non-clear cell RCC who could have received one prior VEGFR-TKI therapy but could not have been previously treated with an immune checkpoint inhibitor or chemotherapy. Four patients (13%) had received prior VEGFR-TKI therapy. All patients received cabozantinib 40 mg daily in combination with atezolizumab.

At a median follow-up of 13 months, ORR per RECIST v1.1 was 33%, and disease control rate was 93%. Median PFS was 9.5 months (95% CI 5.5-NE), and median duration of response was 8.3 months.

Treatment-related grade 3/4 AEs occurred in 37% of patients, and hypophosphatemia (13%) was the most common grade 3/4 AE. Seventeen percent of patients discontinued either study treatment for treatment-related AEs, and 3% discontinued both study treatments for treatment-related AEs.

“Following on our pivotal CheckMate -9ER data, we are thrilled to share these additional findings at the ESMO Virtual Congress 2020 that speak to the potential of cabozantinib in combination with immune checkpoint inhibitor therapy for the treatment of advanced kidney cancer,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “The encouraging durable objective response and disease control rates demonstrated in both of these cohorts build on the positive results we’ve seen for cabozantinib in combination with atezolizumab in other difficult-to-treat tumor types and support the further evaluation of this regimen for the treatment of renal cell carcinoma.”
Source: "Exelixis Announces Results From Two Renal Cell Carcinoma Cohorts Of The COSMIC-021 Trial Of Cabozantinib In Combination With Atezolizumab | Exelixis, Inc.". 2020. Exelixis, Inc.

Related Content:

ESMO Virtual Congress 2020: Cabozantinib in Combination with Atezolizumab in Non-Clear Cell Renal Cell Carcinoma: Results from Cohort 10 of the COSMIC-021 Study

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