Trial results for the Phase 2 study NCT04941287, investigating atezolizumab in combination with CDX-1127 (varlilumab), with or without cobimetinib, for advanced-stage biliary tract cancer, were posted on ClinicalTrials.gov on 2025-05-23. The triple therapy arm (cobimetinib, atezolizumab, varlilumab) showed a median Progression-Free Survival (PFS) of 2.40 months, compared to 1.84 months for the dual therapy arm (atezolizumab, varlilumab).
Background
Atezolizumab is an immunotherapy that works by helping the body's immune system attack cancer cells. Varlilumab (CDX-1127) is an immune agonist antibody intended to further enhance the immune response. Cobimetinib is a kinase inhibitor. This trial investigated these agents for the treatment of advanced-stage biliary tract cancer, including metastatic and recurrent forms of distal bile duct adenocarcinoma, gallbladder carcinoma, and intrahepatic cholangiocarcinoma.
Trial design
The Phase 2 trial (NCT04941287) enrolled 57 participants with advanced-stage biliary tract cancer, specifically metastatic distal bile duct adenocarcinoma, metastatic gallbladder carcinoma, metastatic intrahepatic cholangiocarcinoma, recurrent distal bile duct adenocarcinoma, and recurrent gallbladder carcinoma. The study evaluated two treatment arms: Arm A, consisting of cobimetinib, atezolizumab, and varlilumab; and Arm B, consisting of atezolizumab and varlilumab.
Key results
The trial reported outcomes for Progression-Free Survival (PFS) and adverse events.
- For "Duration of Progression Free Survival (PFS)":
- Participants in Arm A (Cobimetinib, Atezolizumab, Varlilumab) had a median PFS of 2.40 months.
- Participants in Arm B (Atezolizumab, Varlilumab) had a median PFS of 1.84 months.
- Regarding "The Number of Participants Experiencing Grade 3, 4 and 5 Adverse Events":
- In Arm A (Cobimetinib, Atezolizumab, Varlilumab), 1 participant experienced Grade 3, 4, or 5 adverse events in one measurement, and 1 participant in another.
- In Arm B (Atezolizumab, Varlilumab), 2 participants experienced Grade 3, 4, or 5 adverse events in one measurement, and 3 participants in another.
What this means
The results suggest that the addition of cobimetinib to the atezolizumab and varlilumab regimen (Arm A) may lead to a numerically longer median Progression-Free Survival in patients with advanced-stage biliary tract cancer compared to the dual therapy alone (Arm B). The safety profile, as indicated by the number of participants experiencing severe adverse events, appears to be manageable across both arms, though the numbers are small. These findings provide preliminary data for the ongoing investigation of these combination immunotherapies in this challenging cancer type.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04941287, titled "Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer," were posted on 2025-05-23 on clinicaltrials.gov.