Phase 2 Study of Gemcitabine, Cisplatin, Quemliclustat (AB680) and Zimberelimab (AB122) during First-Line Treatment of Advanced Biliary Tract Cancers Big Ten Cancer Research Consortium BTCRC-GI22-564

Inclusion Criteria

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

2. 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.

3. 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.

4. Age ≥ 18 years at the time of consent.

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

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

7. Adequate organ function as detailed in the protocol.

8. 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.

9. 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.

10. 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.

Exclusion Criteria

1. Prior therapy with gemcitabine, cisplatin, or any immune checkpoint inhibitors for the

treatment of BTC.

2. Known hypersensitivity to recombinant proteins, or any excipient contained in

treatment medication formulations.

3. Active autoimmune disease that has required systemic treatment in the past 2 years

(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive

drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid

replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a

form of systemic treatment.

NOTE: participants with asthma who require intermittent use of bronchodilators,

inhaled corticosteroids, or local corticosteroid injections will not be excluded from

this study.

4. History of solid organ or allogeneic bone marrow transplantation.

5. Pregnant or breastfeeding. NOTE: breast milk cannot be stored for future use while the

mother is being treated on study.

6. Patients with a prior or concurrent malignancy whose natural history or treatment has

the potential to interfere with the safety or efficacy assessment of the

investigational regimen are not eligible for this trial.

7. Untreated central nervous system (CNS) metastasis. Screening of asymptomatic patients

for CNS metastasis is not required for enrollment.

8. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, will

make the administration of IP(s) hazardous, including but not limited to

- Interstitial lung disease, including history of interstitial lung disease or

non-infectious pneumonitis.

- Active viral, bacterial, or fungal infections requiring parenteral treatment

within 14 days of the initiation of the study treatments.

9. History of trauma or major surgery within 28 days prior to the first dose of IP. (Note

that placement of central venous access catheter (e.g., port or similar) is not

considered a major surgical procedure.

10. Treatment with palliative radiation therapy within 14 days of study treatment

initiation.

11. Has known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the trial.

12. Significant dementia or other mental condition that precludes the participant's

ability to consent to the study.

13. Use of any live vaccines against infectious diseases within 4 weeks (28 days) of

initiation of investigational products.