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

NCT07793253 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: J2695IRB00560104
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Biliary Tract Cancers; Intrahepatic Cholangiocarcinoma (Icc); Extrahepatic Cholangiocarcinoma; Gallbladder Carcinoma; Ampulla of Vater Carcinoma; Ampullary Carcinoma

Keywords

Daraxonrasib (RMC-6236); KRAS (Kirsten rat sarcoma virus) mutations; Immunotherapy; Biliary Tract Cancer; Liver Cancer; Carcinoma; Metastatic Cancer; Gastrointestinal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response (ORR)

  ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Subjects who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders.

  4 years

Secondary Outcomes (5)

• Overall Survival (OS)

  4 years

• Progression free survival (PFS)

  4 years

• Duration of response (DOR)

  4 years

• Disease control rate (DCR)

  4 years

• Unacceptable Toxicities

  4 years

Study Arms (1)

Daraxonrasib

EXPERIMENTAL

Drug: Daraxonrasib

Interventions

Daraxonrasib DRUG

Daraxonrasib will be taken at a dose of 300 mg orally once daily in 28-day cycles.

Also known as: RMC-6236

Daraxonrasib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Revolution Medicines, Inc.: collaborator
• Cholangiocarcinoma Foundation: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Gallbladder Neoplasms; Liver Neoplasms; Carcinoma; Neoplasm Metastasis; Gastrointestinal Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Diseases

Study Officials

• Nilo Azad, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Colleen Apostal, RN

CONTACT

410-614-3644; GIClinicalTrials@jhmi.edu

Nilo Azad, MD

CONTACT

410-614-9169; nilo.azad@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2030
• Study Completion (Estimated): November 1, 2030
• Last Updated: August 28, 2026

Record last verified: 2026-08

Locations

US (1)