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

Conditions

• Metastatic Distal Bile Duct Adenocarcinoma
• Metastatic Gallbladder Carcinoma
• Metastatic Intrahepatic Cholangiocarcinoma
• Recurrent Distal Bile Duct Adenocarcinoma
• Recurrent Gallbladder Carcinoma
• Recurrent Intrahepatic Cholangiocarcinoma
• Stage IV Distal Bile Duct Cancer AJCC v8
• Stage IV Gallbladder Cancer AJCC v8
• Stage IV Intrahepatic Cholangiocarcinoma AJCC v8
• Unresectable Liver Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — BIOLOGICAL
  Given IV
• Biopsy — PROCEDURE
  Undergo tumor biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Cobimetinib — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo a CT scan
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Varlilumab — DRUG
  Given IV

Study Details

This phase II trial investigates the effect of combining two immune therapies, atezolizumab and CDX-1127 (varlilumab), with or without cobimetinib, in treating patients with biliary tract cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Varlilumab is an immune agonist antibody that may further strengthen the immune system's attack on the cancer. Cobimetinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving atezolizumab in combination with varlilumab and cobimetinib may work better than atezolizumab and varlilumab alone in treating patients with unresectable biliary tract cancer.

Key Dates

Start date

Dec 15, 2021

Status verified

May 2025

Primary completion

Jan 2, 2024

Completion

Apr 29, 2026

Study Design

Enrollment

57 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A (cobimetinib, atezolizumab, varlilumab)
  Patients receive cobimetinib PO QD on days 1-21 of each cycle, atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle, and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.
• Experimental: Arm B (atezolizumab, varlilumab)
  Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 of each cycle and varlilumab IV over 90 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI at baseline, every 8 weeks while on treatment, and at end of treatment or progression. Patients also undergo a tumor biopsy at baseline and on day 21 of cycle 1. Patients also undergo blood sample collection on study.

Primary Outcome Measure

Number of Participants Experiencing a Response [ Time Frame: Up to 2 years ]

Locations (29)

Related coverage on Hipa.ai

• Atezolizumab Triple Therapy Shows Longer PFS vs Dual in Biliary Tract Cancer
  Atezolizumab · May 23, 2025 · ClinicalTrials.gov

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