February 03, 2022
A phase II study led by investigators at The University of Kansas Cancer Center shows promising efficacy in people with metastatic colorectal cancer who have tried standard systemic chemotherapy, but it did not work.
Anwaar Saeed, MD, associate professor in the Department of Medical Oncology and associate director of the Early Phase Program at the cancer center, is studying a drug combination that has the potential to prolong the life of patients with advanced-stage colorectal cancer. She and her team are exploring the efficacy of cabozantinib, a small molecule inhibitor, in combination with durvalumab, an immunotherapy drug. Cabozantinib targets a protein, called vascular endothelial growth factor (VEGF), which helps tumors grow new blood vessels.
“There is growing clinical evidence supporting the efficacy of cabozantinib plus immunotherapy combinations in other disease types like renal cell carcinoma, hepatocellular carcinoma, non-small cell lung cancer and others. Considering the known activity of VEGF-targeted therapy in some gastrointestinal cancers, we proposed that combining cabozantinib with durvalumab will lead to clinical synergy in this patient population,” Dr. Saeed said.
Called CAMILLA, the investigator-initiated trial is studying the drug combination in people with colorectal cancer, gastric and esophageal cancer and hepatocellular carcinoma, a type of liver cancer. After phase Ib results of the gastrointestinal cancer basket CAMILLA trial demonstrated promising safety and efficacy, the study expanded to a phase II, multicohort, multicenter trial of 117 patients. The cohort involving colorectal cancer patients is the furthest along; Dr. Saeed recently discussed the results at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.
The results show encouraging efficacy and safety data in this cohort of patients with advanced colorectal cancer. Survival rates were particularly high among participants with RAS wild type cancer. Patients with RAS wild type means their RAS gene is not mutated.
The colorectal cancer cohort included 29 participants with results revealing an overall response rate of 27.6%, confirmed partial response rate of 20.7% and disease control rate of 86.2%. Investigators reported median progression-free survival, which means the cancer did not worsen, of 3.8 months and median overall survival of 9.1 months. About 34% of patients went six months without their cancer worsening. In the subgroup of patients with RAS wild type, investigators observed an overall response rate of 50%, median progression-free survival of 6.3 months and median overall survival of 21.8 months.
The RAS wild-type population findings from CAMILLA prompted deeper analysis of data from another clinical study that was presented at the 2022 ASCO GI Cancers Symposium.
“Results from cohort 16 of the COSMIC-021 trial that examined cabozantinib plus PD-L1 inhibitor atezolizumab in advanced pretreated colorectal cancer patients revealed similar findings that those with RAS wild type also experienced higher survival rates - a median progression-free survival of around six months,” Dr. Saeed said. “While the results won’t change how we practice in oncology clinics today, it definitely highlights the potential for this combination to change the current practice if the same positive outcome is confirmed in upcoming pivotal trials."
Nearly a quarter of colorectal cancer cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 15%. Progression-free survival is around six weeks and median overall survival is about seven to eight months with the currently available agents. According to Dr. Saeed, results from CAMILLA and COSMIC-021 suggest possibility of higher survival rates with cabozantinib plus immunotherapy.
A global trial
Up next, Dr. Saeed and other investigators will lead a randomized trial examining a similar combination against the standard of care therapy in third line setting in patients with advanced microsatellite stable (MSS) colorectal cancer. Patients with metastatic colorectal cancer who have MSS and/or mismatch repair-proficient tumors tend to have poor responses to immune checkpoint inhibitor monotherapy. Called STELLAR 303, the phase III trial will be available at sites across the globe. About 600 participants will enroll in the trial.
“We are thrilled and looking forward to the launch of the STELLAR 303 trial later this year. This trial will examine XL092, a next-generation multi-tyrosine kinase inhibitor that targets cancer growth like cabozantinib, in combination with atezolizumab versus regorafenib in this population,” Dr. Saeed said.