Phase 2 Study of Daraxonrasib in Recurrent KRAS-Mutant Biliary Tract Cancer

A Multi-Institutional Phase 2 Evaluation of Daraxonrasib in Recurrent KRAS-Mutant Biliary Tract Cancer

The purpose of this study is to evaluate the anti-tumor efficacy of daraxonrasib monotherapy in patients with unresectable or advanced/metastatic, KRAS-mutant BTC who have progressed on or are intolerant of 1st line systemic therapy.

Inclusion Criteria:

• Unresectable locally advanced or metastatic histologically or cytologically confirmed biliary tract cancer
• Must have documented disease progression or intolerance of one prior systemic chemotherapy regimen (with or without immunotherapy) for unresectable and/or advanced stage disease.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
• Have measurable disease based on RECIST 1.1.
• Documented KRAS mutation
• Adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• Willingness to provide serial tissue and blood samples for mandatory translational research.
• Evidence of post-menopausal status or a negative pregnancy test in women of childbearing potential (WOCBP).
• All participants must agree to use acceptable form of birth control while on study.
• Ability to take oral medications and willingness to keep daily adherence record in a medication diary.
• Must understand the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form in accordance with regulatory and institutional guidelines.

Exclusion Criteria:

• Any systemic anti-cancer therapy for advanced BTC within 3 weeks of enrollment or 5 half-lives of the drug, whichever is shorter.
• Prior treatment with any KRAS, RTK, or MEK inhibitor or other RAS-pathway targeting signal transduction inhibitor agents
• Major surgery, extended field radiotherapy, or local regional therapy within 4 weeks from first dose of study drug, limited field radiotherapy within 2 weeks of first dose, or failure to recover from side effects of these prior therapies
• Known additional malignancy that is progressing and requires active treatment.
• Receiving concomitant medications that interfere with Daraxonrasib.
• Significant cardiovascular disease.
• Significant cardiac conduction abnormalities.
• Impaired gastrointestinal function.
• Active autoimmune disease
• Clinically active ascites.
• Active uncontrolled infection requiring systemic therapy within 72 hours prior to C1D1.
• Known history of human immunodeficiency virus (HIV).
• Active or chronic hepatitis B or hepatitis C.
• Known history of central nervous system (CNS) metastases and/or history of uncontrolled seizures.
• Any uncontrolled acute or chronic medical illness.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Pregnant or breastfeeding
• Patient is unwilling or unable to follow the study schedule for any reason.
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial.