Exelixis, Inc. (Nasdaq: EXEL) today announced results for cabozantinib (CABOMETYX®) in combination with immunotherapies in patients with advanced colorectal cancer, including encouraging data from cohort 16 of the phase 1b COSMIC-021 trial of cabozantinib in combination with atezolizumab in patients with metastatic colorectal cancer who were previously treated with fluoropyrimidine-containing chemotherapy. Results from cohort 2 of the phase 2 CAMILLA trial of cabozantinib in combination with durvalumab in patients with advanced mismatch repair proficient/micro satellite stable (pMMR/MSS) colorectal cancer patients who were chemotherapy-refractory were also announced. The data from these studies are being presented during Poster Session C: Cancers of the Colon, Rectum, and Anus on Saturday, January 22 at the 2022 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI).
Abstract 121: A phase 1b multi-tumor cohort study of cabozantinib plus atezolizumab in advanced solid tumors (COSMIC-021): Results of the colorectal cancer cohort
At a median follow-up of 28.1 months, the primary endpoint of objective response rate (ORR) by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in cohort 16 (n=31) was 10%. The disease control rate (DCR; complete response + partial response + stable disease) was 71%. Median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI]: 2.7-5.4), and median overall survival (OS) was 14.0 months (95% CI: 5.5-16.7). Median duration of response was 7.6 months (95% CI: 4.2-not estimable [NE]).
A post-hoc exploratory analysis showed that patients with wild-type RAS (n=12) had longer PFS and OS compared with patients with RAS mutations (n=19): median PFS was 5.8 months (95% CI: 2.8-11.0) compared with 2.7 months (95% CI: 1.6-4.1), respectively, and median OS was 16.7 months (95% CI: 8.4-NE) compared with 8.7 months (95% CI: 4.7-15.9), respectively. ORR was 25% for patients with wild-type RAS and 0% for patients with RAS mutations.
“Colorectal cancer is a serious disease affecting more than 150,000 people in the U.S., about a quarter of whom have metastatic disease when diagnosed,” said Thomas A. Abrams, M.D., Assistant Professor of Medicine, Harvard Medical School, Senior Physician, Dana-Farber Cancer Institute, and lead investigator. “Metastatic colorectal cancer becomes more challenging to treat following disease progression on chemotherapy. Data from cohort 16 of COSMIC-021 are encouraging for clinicians and patients, as they show the potential utility of cabozantinib in combination with atezolizumab to help patients with metastatic colorectal cancer who have already progressed on at least one line of fluoropyrimidine-containing therapy.”
Eligible patients had metastatic colorectal cancer with an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 and had progressed during or following systemic chemotherapy, including fluoropyrimidine plus oxaliplatin or irinotecan. Patients were allowed to have received up to two prior lines of anti-cancer therapy, including EGFR-targeted therapy. Patients with known microsatellite instability high and/or mismatch repair-deficient disease were excluded. Sixty-one percent of patients had an ECOG Performance Status of 1, 71% had received two prior lines of therapy and 94% had visceral disease, including 81% with liver metastases.
The most common treatment-related adverse events (AEs) were diarrhea (52%), fatigue (42%) and nausea (35%). Grade 3/4 treatment-related AEs occurred in 52% of patients. The most common grade 3/4 treatment-related AEs were hypertension (10%), fatigue (6%) and lipase increased (6%). No grade 5 events were reported. Six percent of patients discontinued both cabozantinib and atezolizumab due to treatment-related AEs; 6% discontinued cabozantinib only and 6% discontinued atezolizumab only.
Abstract 135: Phase II trial of cabozantinib (Cabo) plus durvalumab (Durva) in chemotherapy refractory patients with advanced mismatch repair proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC): CAMILLA CRC cohort results
Of the 36 patients enrolled in cohort 2 of the CAMILLA trial, 29 were evaluable for the efficacy analysis. The primary outcome of investigator-assessed ORR per modified RECIST version 1.1 was 27.6%. The confirmed partial response rate was 20.7%, and the DCR was 86.2%. Median PFS was 3.8 months (95% CI: 3.4-6.3), with a 6-month PFS of 34.5% (95% CI: 17.9-54.3). Median OS was 9.1 months (95% CI: 5.8-21.8). In a subgroup analysis of those with wild-type RAS (n=12), ORR was 50.0%, and DCR was 83.3%. Median PFS was 6.3 months (95% CI: 1.8-NE), and median OS was 21.8 months (95% CI: 4.5-NE).