Biliary Tract Cancers, Intrahepatic Cholangiocarcinoma (Icc), Extrahepatic Cholangiocarcinoma, Gallbladder Carcinoma, Ampulla of Vater Carcinoma, Ampullary Carcinoma
Conditions
Keywords
Daraxonrasib (RMC-6236), KRAS (Kirsten rat sarcoma virus) mutations, Immunotherapy, Biliary Tract Cancer, Liver Cancer, Carcinoma, Metastatic Cancer, Gastrointestinal Cancer
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.
Interventions
DRUGDaraxonrasib
Daraxonrasib will be taken at a dose of 300 mg orally once daily in 28-day cycles.
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Revolution Medicines, Inc.
Cholangiocarcinoma Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (ORR) | 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 4 years | OS is defined as the number of months from the date of treatment initiation until death from any cause or end of follow-up. OS will be censored on the date the participant was last known to be alive for participants without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve. |
| Progression free survival (PFS) | 4 years | PFS is defined as the number of months from the date of treatment initiation to radiographic disease progression using RECIST v1.1 criteria or death due to any cause, whichever occurs first. Progression of disease (PD) will be censored at the date of the last scan for participants without documentation of disease progression at the time of analysis. Progression will be censored at the time of treatment initiation for participants that do not have a follow up scan. Estimation based on the Kaplan-Meier curve. |
| Duration of response (DOR) | 4 years | DOR, defined as the number of months from the date of response to the date of clinically determined disease progression or death from any cause, in participants achieving CR or PR. |
| Disease control rate (DCR) | 4 years | DCR is defined as the proportion of participants who achieved CR, PR and stable disease (SD). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. |
| Unacceptable Toxicities | 4 years | Number of participants experiencing treatment-related adverse events requiring treatment discontinuation. Defined using NCI CTCAE version 6.0 |
Countries
United States
Contacts
CONTACTColleen Apostal, RN
CONTACTNilo Azad, MD
PRINCIPAL_INVESTIGATORNilo Azad, MD
Johns Hopkins University
Outcome results
None listed