Combination therapy for advanced biliary tract cancers

Study of Gemcitabine, Cisplatin, Quemliclustat (AB680) and Zimberelimab (AB122) During First-line Treatment of Advanced Biliary Tract Cancers (QUIC)

This study is testing a new combination of medications to see if it can help people with advanced biliary tract cancers feel better and manage their disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Big Ten Cancer Research Consortium (Academic / other)
• Drugs / interventions: radiation, zimberelimab
• Locations: 4 sites (Indianapolis, Indiana and 3 other locations)
• Trial ID: NCT06048133 on ClinicalTrials.gov

What this trial studies

This phase 2 study investigates the safety and efficacy of a combination therapy involving gemcitabine, cisplatin, zimberelimab (AB122), and quemliclustat (AB680) in patients with untreated advanced biliary tract cancers. The trial includes a safety run-in phase with 6 participants to monitor early safety signals before full enrollment. Participants will receive 4 cycles of treatment, after which cisplatin will be discontinued while the other medications continue until disease progression or intolerable side effects occur. The study aims to enroll up to 39 participants in total.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed late-stage biliary tract carcinoma who have not received prior systemic treatment for advanced disease.

Not a fit: Patients with early-stage biliary tract cancers or those who have previously received systemic treatment for advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced biliary tract cancers.

How similar studies have performed: Other studies have shown promise with similar combination therapies in treating advanced cancers, suggesting potential for success in this approach.

Eligibility criteria

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. NOTE: Biliary cancer may secrete hormones to produce a false-positive pregnancy test. Female subjects of childbearing potential with a positive pregnancy test should have a thorough history and additional work up as determined by the treating physician to rule out pregnancy (e.g. serial βHCG measurements, ultrasound). Once pregnancy has been ruled out, the subject may proceed with screening and enrollment.
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 14 months 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 11 months 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.

Where this trial is running

Indianapolis, Indiana and 3 other locations

• Indiana University Melvin and Bren Simon Comprehensive Cancer Center — Indianapolis, Indiana, United States (Recruiting)
• University of Michigan Health System — Ann Arbor, Michigan, United States (Recruiting)
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States (Recruiting)
• University of Wisconsin — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Nataliya Uboha, MD, PhD — University of Wisconsin, Madison
• Study coordinator: Nataliya Uboha, MD, PhD

Conditions Biliary Tract Carcinoma; Cholangiocarcinoma; Bile Duct Cancer