NCT04941287

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

A Randomized Phase 2 Study of Combination Atezolizumab and CDX-1127 (Varlilumab) With or Without Addition of Cobimetinib in Previously Treated Unresectable Biliary Tract Cancers

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To assess the response rate (ORR) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib. II. To assess the progression free survival (PFS) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib in patients with unresectable, pre-treated biliary cancers. II. To assess overall survival (OS) of patients with unresectable, pre-treated biliary cancers treated with the combination of atezolizumab and CDX-1127 (varlilumab) with or without cobimetinib. III. To determine the effect of combination atezolizumab and CDX-1127 (varlilumab) +/- cobimetinib on T cell subpopulations systemically and intratumorally. CORRELATIVE OBJECTIVES: I. To explore the effect of atezolizumab and CDX-1127 (varlilumab) +/- cobimetinib on local and systemic immune activation pathways, immune suppressive pathways, and cytokine/chemokine signaling in peripheral blood and within the tumor microenvironment. II. To assess whether atezolizumab and CDX-1127 (varlilumab) clearance at baseline and over time correlate with clinical outcomes (ORR, PFS and OS) and the presence of cachexia. III. To assess immunogenicity by monitoring for the presence of anti-drug antibodies (ADA) to both atezolizumab and CDX-1127 (varlilumab). OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive cobimetinib orally (PO) once daily (QD) on days 1-21 of each cycle, atezolizumab intravenously (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 computed tomography (CT) or magnetic resonance imaging (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. ARM B: 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. After completion of study treatment, patients are followed up at 30 days and then every 3 months until death, withdrawal of consent, or study closure.

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

Interventions

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

Timeline

• Start date: 2021-12-15
• Primary completion: 2024-01-02
• Completion: 2026-04-29
• First posted: 2021-06-28
• Last updated: 2025-05-23
• Results posted: 2025-05-23

Locations

29 sites across 1 country: United States

Regulatory

• FDA-regulated drug study