Cabometyx (cabozantinib) plus Imfinzi (durvalumab) Achieves 86% Disease Control Rate in Chemorefractory pMMR/MSS Metastatic Colorectal Cancer

News on January 22, 2022 /BioValleyBIOON/ --Exelixis, Inc. recently announcedTyrosine Kinase Inhibitor (TKI) Cabometyx (cabozantinib)Results of Combination Immunotherapy in Patients with Advanced Colorectal Cancer (CRC), Including Data from Cohort 2 (Colorectal Cancer Cohort) of the Phase 2 CAMILLA Trial. The trial is evaluating Cabometyx.UnitedAstraZenecaAnti-PD-L1 Therapy Imfinzi(Imfinzi, generic name: durvalumab) treatmentChemotherapy-refractory advanced mismatch repair-proficient/microsatellite stable (pMMR/MSS) CRCPatient.

Mismatch repair status and microsatellite instability status are considered prognostic factors for CRC and can influence treatment decisions.With microsatellite stability (MSS) and/or mismatch repair proficiency (pMMR)TumorPatients with metastatic CRC often show poor response to single-agent immune checkpoint inhibitors., which means that alternative treatment strategies are needed.

The CAMILLA trial cohort 2 enrolled patients with advanced pMMR/MSS colorectal cancer (CRC) who had previously received two or more treatments but experienced disease progression, with 90% of the patients being in the Eastern region.TumorThe Eastern Cooperative Oncology Group (ECOG) performance status was 1, 41% of patients had wild-type RAS, and 79% had liver metastases. Approximately half (52%) of the patients had received at least three prior treatments.

Of the 36 patients enrolled in Cohort 2, 29 were evaluable for efficacy. The investigator assessments were determined according to the modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1).The objective response rate (ORR) was 27.6%, and the disease control rate (DCR; complete response + partial response + stable disease) was 86.2%. The median progression-free survival (PFS) was 3.8 months (95% CI: 3.4-6.3), and the median overall survival (OS) was 9.1 months (95% CI: 5.8-21.8).。Subgroup analysis of wild-type RAS patients (n=12) showed an ORR of 50.0%, DCR of 83.3%, median PFS of 6.3 months (95% CI: 1.8-not estimable [NE]), and median OS of 21.8 months (95% CI: 4.5-NE).

Among 36 patients evaluable for safety, the most common treatment-related adverse events were grade 1/2 fatigue (53%), nausea (42%), diarrhea (36%), anorexia (31%), and hand-foot syndrome (25%). Eleven patients (31%) experienced treatment-related adverse events of grade 3 or higher. Immune-related adverse events of grade 3 or higher occurred in 16.6% of patients. One patient discontinued Imfinzi due to adverse events; no patients discontinued Cabometyx.

Previously, Exelixis also announcedCabometyx in combination with Roche's anti-PD-L1 therapy Tecentriq(Tecentriq, generic name: atezolizumab, Atezolizumab) encouraging data from Cohort 16 of the Phase 1b COSMIC-021 trial for the treatment of advanced solid tumors. Cohort 16 (n=31) enrolled patients withMetastatic colorectal cancer (mCRC) with disease progression during or after prior systemic chemotherapy (including fluorouracil + oxaliplatin or irinotecan)Patients, these patients in the eastern partTumorPatients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were allowed to have received up to two prior anticancer therapies, including EGFR-targeted agents. Sixty-one percent of patients had an ECOG performance status of 1, 71% had received two prior lines of therapy, 94% had visceral disease, and 81% had liver metastases.

The results showed that, in this cohort, the Cabometyx+Tecentriq regimen demonstrated encouraging clinical activity and manageable safety. The specific data were as follows: median follow-up of 28.1 months,ORR was 10%, DCR was 71%, median PFS was 3.0 months (95% CI: 2.7-5.4), median OS was 14.0 months (95% CI: 5.5-16.7), and median duration of response (DOR) was 7.6 months.(95% CI: 4.2-Not Estimable [NE]). Post-hoc exploratory analysis showed that,Patients with wild-type RAS (n=12) showed longer PFS and OS outcomes compared to patients with mutant RAS (n=19): median PFS (5.8 months vs 2.7 months), median OS (16.7 months vs 8.7 months). The ORR in wild-type RAS patients was 25%, while the ORR in RAS mutant patients was 0%.

Vicki L. Goodman, M.D., Executive Vice President of Product Development and Medical Affairs and Chief Medical Officer of Exelixis, stated: "Patients with previously treated advanced colorectal cancer need more treatment options to help manage their disease. We are pleased that the results from cohort 16 of COSMIC-021 and cohort 2 of CAMILLA confirm the potential of Cabometyx in combination with immunotherapy for the treatment of advanced colorectal cancer, a patient population that often faces poor prognosis." (Bioon.com)

Source of the original text:Exelixis Announces Detailed Results for Cabozantinib in Combination with Immunotherapies in Patients with Advanced Colorectal Cancer at ASCO GI 2022