Study of Gemcitabine, Cisplatin, AB680 and AB122 During First Line Treatment of Advanced Biliary Tract Cancers (QUIC)

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. Prioradjuvant therapy is allowed as long as recurrences occurred 6 months or later fromall treatment completion.

3. Written informed consent and HIPAA authorization for release of personal healthinformation. NOTE: HIPAA authorization may be included in the informed consent orobtained 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 fathera child must have a negative pregnancy test (serum or urine) within 14 days prior toregistration. NOTE: Biliary cancer may secrete hormones to produce a false-positivepregnancy test. Female subjects of childbearing potential with a positive pregnancytest should have a thorough history and additional work up as determined by thetreating physician to rule out pregnancy (e.g. serial βHCG measurements,ultrasound). Once pregnancy has been ruled out, the subject may proceed withscreening and enrollment.

9. Females of childbearing potential who are sexually active with a male able to fathera child must be willing to abstain from heterosexual vaginal intercourse or use aneffective method(s) of contraception from the time of informed consent, during thestudy and for up to 14 months after the last dose of study drug(s). Males able tofather a child must be willing to abstain from heterosexual vaginal intercourse orto use an effective method(s) of contraception from initiation of treatment, duringthe study and for up to 11 months after the last dose of study drug(s). See theprotocol for specific timeframes for each drug.

10. Ability of the subject to understand and comply with study procedures for the entirelength 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 forthe treatment of BTC.

2. Known hypersensitivity to recombinant proteins, or any excipient contained intreatment 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 immunosuppressivedrugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is not considereda form of systemic treatment. NOTE: participants with asthma who require intermittent use of bronchodilators,inhaled corticosteroids, or local corticosteroid injections will not be excludedfrom 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 whilethe mother is being treated on study.

6. Patients with a prior or concurrent malignancy whose natural history or treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are not eligible for this trial.

7. Untreated central nervous system (CNS) metastasis. Screening of asymptomaticpatients for CNS metastasis is not required for enrollment.

8. Underlying medical conditions that, in the Investigator's or Sponsor's opinion, willmake the administration of IP(s) hazardous, including but not limited to

• Interstitial lung disease, including history of interstitial lung disease ornon-infectious pneumonitis.

• Active viral, bacterial, or fungal infections requiring parenteral treatmentwithin 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) isnot considered a major surgical procedure.

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

11. Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

12. Significant dementia or other mental condition that precludes the participant'sability to consent to the study.

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