Title
Phase 2 Study of Gemcitabine, Cisplatin, AB680 and AB122 during first line treatment of advanced biliary tract cancers: BTCRC-GI22-564

Description
This is a phase 2 study of gemcitabine, cisplatin, zimberelimab (AB122) and quemliclustat (AB680) in subjects with untreated advanced biliary tract cancers (BTC). The study will include a safety run-in involving 6 study participants. The goal of the safety run-in is to screen for early safety signals of the proposed drug combination. Trial enrollment can continue while full safety assessment is being completed for the first 6 subjects.

Participants will receive 4 cycles of combination therapy as described. After 4 cycles (~6 months), cisplatin will be discontinued, while gemcitabine, zimberelimab (AB122), and quemliclustat (AB680) will be continued. Subjects will be treated until disease progression or development of intolerable toxicities. In total, there will be up to 39 participants on the study.

Objective
Primary Objective:
1. Estimate the Progression Free Survival (PFS) for combination treatment with Gemcitabine, Cisplatin, quemliclustat (AB680) and zimberelimab (AB122) in advanced biliary tract cancers (BTC).

Secondary Objectives:
1. Estimate the Overall Survival (OS).
2. Estimate the Objective Response Rate (ORR).
3. Estimate the Disease Control Rate (DCR).
4. Estimate the Duration of Response (DOR).
5. Evaluate the Safety of the studied drug combination.

Treatment Drug: Gemcitabine
Drug: Cisplatin
Drug: Zimberelimab
Drug: Quemliclustat

Key Eligibility Inclusion Criteria:

Patients with cytologically or histologically confirmed BTC by AJCC version 8.

Patients must have late stage (locally advanced, recurrent or metastatic) BTC. Patients must not have received systemic treatment for advanced disease. Prior adjuvant therapy is allowed as long as recurrences occurred 6 months or later from all treatment completion.

Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Age >/= 18 years at the time of consent.

ECOG Performance Status of 0-2 within 28 days prior to registration.

Presence of measurable or evaluable disease, as defined by RECIST v1.1.

Adequate organ function as detailed in the protocol.

Females of childbearing potential who are sexually active with a male able to father a child must have a negative pregnancy test (serum or urine) within 14 days prior to registration.

Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from heterosexual vaginal intercourse or use an effective method(s) of contraception from the time of informed consent, during the study and for up to 120 days after the last dose of study drug(s). Males able to father a child must be willing to abstain from heterosexual vaginal intercourse or to use an effective method(s) of contraception from initiation of treatment, during the study and for up to 120 days after the last dose of study drug(s). See the protocol for specific timeframes for each drug.

Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.

Applicable Disease Sites
Gastrointestinal cancers, other

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital