GEN-001 Plus Pembrolizumab for Patients With Advanced Refractory Biliary Tract Cancer

Study Overview
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Brief Summary
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This is a phase II, multicenter, open-label study with a safety run-in to evaluate the safety and efficacy of GEN-001 in combination with pembrolizumab or in combination with pembrolizumab and mFOLFOX for patients with advanced refractory BTC who have progressed after 1 or 2 prior standard therapy and are not candidates for any other standard therapy. The safety run-in phase will be conducted before the main study phase

Official Title
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A Phase II Study to Evaluate the Safety and the Efficacy of GEN-001 in Combination With Pembrolizumab for Patients With Advanced Refractory Biliary Tract Cancer

Conditions
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Biliary Tract Cancer

Intervention / Treatment
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* Drug: GEN-001
* Drug: Pembrolizumab
* Drug: mFOLFOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. Be ≥19 years of age on day of signing informed consent. Patient with histologically or cytologically confirmed diagnosis of unresectable, recurrent, or metastatic advanced biliary tract adenocarcinoma of the gallbladder or biliary tree (either intrahepatic or extrahepatic cholangiocarcinoma) Exclusion Criteria: A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (Cohort 1 only), and was discontinued from the previous IO therapy due to a Grade 3 or higher immune-related AE (irAE) (Cohort 2 and Cohort 3). Is currently participating and receiving study treatments or has participated in a study of an investigational agent and received the study therapy or has used an investigational device within 4 weeks prior to the first dose of study treatment. Has had an allogeneic tissue/solid organ transplan

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GEN-001 with pembrolizumab or GEN-001 with pembrolizumab and mFOLFOX<br>Drug: GEN-001 Drug: pembrolizumab Drug: mFOLFOX | Drug: GEN-001<br>* The capsules taken by mouth. Each capsule will contain ≥ 3x10^11 colony-forming units (CFU)<br>Drug: Pembrolizumab<br>* 200 mg given by intravenous (IV) infusion once every 3 weeks<br>* Other names: Keytruda;Drug: mFOLFOX<br>* mFOLFOX given by intravenous (IV) once every 2 weeks for only cohort 3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The recommended Phase 2 dose (RP2D) of GEN-001 in patients with advanced refractory biliary tract cancer (BTC), when administered as combined with pembrolizumab or as combined with pembrolizumab and mFOLFOX. | Incidence of dose-limiting toxicity (DLT) | 1 years | 
| Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by the Investigator. | The assessment of the anti-tumor activity per cohort | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Event (AE)s and laboratory abnormalities per National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) v.5.0. cohort. | The assessment the overall safety and tolerability per cohort. | 1 years | 
| Duration of Response (DoR) | the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first | 1 years | 
| Progression-free Survival (PFS) | the time from the start date of treatment to the date of PD by RECIST v1.1 or death due to any cause, whichever occurs first | 1 years | 
| Overall Survival (OS) | the time from the start date of treatment to the date of death | 1 years |