Biliary Tract Cancer (BTC)Phase 2NCT07908550
Daraxonrasib in Asian RAS-mutant Biliary Tract Cancer
A Phase 2 study testing Daraxonrasib in people with Biliary Tract Cancer (BTC), run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
Trial summary
The trial will assess the efficacy, safety, and tolerability of daraxonrasib monotherapy in Asian patients with RAS-mutated advanced biliary tract cancer in second-line treatment. The Primary Endpoint is Objective Response Rate (ORR). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Biliary Tract Cancer (BTC)
- What is being tested?
- Daraxonrasib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2027to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years at the time of consent.
- Histologically or cytologically confirmed unresectable locally advanced and/or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, and carcinoma of the Ampulla of Vater, that has progressed or recurred after prior therapy.
- Documented pathogenic RAS (KRAS, NRAS, or HRAS) mutations confirmed by a CAP or CLIA-certified assay from tumor tissue or plasma.
- Progression or intolerance of first-line systemic chemotherapy lines (with or without immunotherapy) for unresectable and/or advanced stage disease. Prior systemic therapy administered in the adjuvant or neoadjuvant context may be considered as a prior line of therapy if disease recurrence or progression occurred during or within 6 months after the last dose of the systemic therapy.
- Radiographically measurable or evaluable disease per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 prior to registration.
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- Adequate organ function as defined by the following:
- Absolute neutrophil count (ANC) ≥ 1.5 × 10³/uL
- Platelet count ≥ 75 × 10³/uL
- Hemoglobin ≥ 8 g/dL
- Total bilirubin ≤ 2 × upper limit of normal (ULN) (except participants with Gilbert Syndrome who must have a total bilirubin level of ≤ 3.0 x ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN, or ≤ 5.0 × ULN in the presence of liver metastases
- Calculated creatinine clearance ≥ 45 mL/min (CKD-EPI equation or other equation per institutional guidelines, or based on 24-hour urine collection.)
Who cannot join
- Receipt of any systemic anti-cancer therapy for advanced BTC within 3 weeks of allocation/randomization or 5 half-lives of the drug (whichever is longer).
- Prior treatment with any RAS pathway inhibitor, including any KRAS, MEK, or receptor tyrosine kinase (RTK) inhibitor (or other RAS-pathway targeting agents).
- Concurrent use of strong CYP3A4 modulators or drugs that strongly inhibit/induce P-gp or BCRP, if alternatives are not feasible.
- Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies:
- Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy).
- Radiotherapy (any dose) for extended field within 4 weeks or limited-field radiotherapy within 2 weeks, and/or has not recovered from acute impact of radiotherapy. Note: evaluable lesion must be outside the treated field.
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- Local-regional therapy (e.g., TACE, SIRT, or ablation) within 4 weeks. Note: evaluable lesion must be outside the treated field.
- Known CNS (central nervous system) metastases or history of uncontrolled seizures. Participants with treated CNS metastases are eligible if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period, and without steroid requirement (with the exception of low-dose steroid use for reasons such as appetite stimulant).
- Known diagnosis of an additional malignancy that is progressing or requires active treatment, with the exception of individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen as agreed upon by the Investigator (e.g., non-melanoma skin cancer, carcinoma in situ of the breast or cervix).
- Pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site
Kaohsiung Medical University Hospital
Kaohsiung City
Li-Tzong Chen, MD, PhD, +886-7-3121101, leochenk153@gmail.com
About this study
Official title: A Phase 2, Open-Label Study of Daraxonrasib Monotherapy as Second-line Treatment in Asian Patients With RAS-mutant Advanced Biliary Tract Cancer
The trial will assess the efficacy, safety, and tolerability of daraxonrasib monotherapy in Asian patients with RAS-mutated advanced biliary tract cancer in second-line treatment. The Primary Endpoint is Objective Response Rate (ORR).
Read the detailed description
After progression on first-line therapy, second-line treatment options for BTC remain limited, with standard regimens such as FOLFOX demonstrating modest efficacy (ORR ~5%, median OS 6.2 months) for those without druggable mutations. KRAS mutations are present in over 15% of BTC cases and are associated with poorer outcomes compared to KRAS wild-type. Daraxonrasib is a first-in-class multi-selective RAS(ON) inhibitor that has shown encouraging activity in KRAS-mutated cancers, including ORRs of 27-36% and median PFS up to 8.8 months in early-phase trials for metastatic pancreatic cancer, providing strong rationale to evaluate daraxonrasib in BTC.
The trial will assess the efficacy, safety, and tolerability of daraxonrasib monotherapy in patients with RAS-mutated advanced biliary tract cancer in second-line treatment.
- Primary Endpoint: Objective Response Rate (ORR).
- Secondary Endpoints: Progression-Free Survival (PFS); Overall Survival (OS); Duration of Response (DOR); Disease Control Rate (DCR); Adverse Event Profile (AEs); Quality of Life (QoL).
This is an open-label, single-arm study using Bayesian Optimal Phase II Design (N=55). Patients will be treated with daraxonrasib at 300 mg QD with continuous dosing in 28-day cycles. Competitive enrollment applies; however, a minimum of 6 patient slots is mandated for Japan. The trial tests a null hypothesis of a 5% response rate versus an alternative of 20%, with one-sided α < 0.05 and >90% power. An interim analysis occurs after 20 patients: if ≤1 response is observed, the trial stops for futility; if ≥2 responses are observed, enrollment continues to 55 patients. If ≥6 responses are observed among 55 patients, the treatment is considered promising. The interim decision is based on confirmed responses per RECIST v1.1. Enrollment continues while the interim analysis is pending so that the study timeline is preserved; only the first 20 patients contribute to the interim decision, and accrual during that period is capped at 16 additional patients (36 enrolled in total).
- Conditions
- Biliary Tract Cancer (BTC)
- Being tested
- Daraxonrasib
- Keywords
- RAS, second-line
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaraxonrasibDrug
Daraxonrasib 300 mg orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Daraxonrasib | Experimental | Not described Receives: Drug: Daraxonrasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR determined by the Investigator based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Each patient will be assigned a best overall response of one of the following RECIST categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE). A patient's best overall response will be determined from all tumor assessments performed from the date of treatment initiation until confirmed disease progression or study discontinuation for any reason, whichever occurs first.
Measured: 2 years
Secondary outcomes (6)
Disease Control Rate (DCR)
The proportion of patients who achieve confirmed CR, PR, or SD for at least 8 weeks.
Measured: 2 years
Progression-Free Survival (PFS)
The time from the start of treatment to either radiographic disease progression or death from any cause. Censoring rules and progression date definitions will follow the FDA's Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics (2007).
Measured: 3 years
Overall Survival (OS)
The time from the start of treatment until death from any cause.
Measured: 4 years
Duration of Response (DOR)
The period from the first documented response (CR or PR per RECIST v1.1 as assessed by the Investigator) until documented tumor progression or death, whichever occurs first.
Measured: 3 years
Safety Profile
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), as well as clinical laboratory tests and vital sign abnormalities. Toxicity will be graded according to the NCI CTCAE version 5.0.
Measured: 2 years
Quality of Life (QoL)
EQ-5D-5L, EORTC QLQ-C30, and EORTC QLQ-BIL21 will be assessed at baseline (C1D1) and every 8 weeks thereafter alongside tumor evaluations up to C5D1 (no QoL assessment from Cycle 6 onward), regardless of study drug interruptions
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2026
- Study startJan 2027 (estimated)
- Primary completionDec 2029 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract Cancer (BTC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Center, Japan, Kanagawa Cancer Center, National Cancer Center Hospital East, Taipei Veterans General Hospital, Taiwan, National Taiwan University Hospital, China Medical University Hospital, Taichung Veterans General Hospital, National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07908550
- Sponsor's protocol ID
- 111169
- Status last verified
- Oct 2026
- First submitted
- 26 Oct 2026
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, Hammel P, Cremolini C, Manji GA, Oberstein PE, Garrido-Laguna I, Springfeld C, Azad NS, Ueno M, Chui SY, Zhang Y, Patel H, Lee Y, Salman Z, Wolpin BM; RASolute 302 Trial Investigators. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 Jul 23;395(4):325-337. doi: 10.1056/NEJMoa2605555. Epub 2026 May 31.
PubMed 42223072
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label Study of Daraxonrasib Monotherapy as Second-line Treatment in Asian Patients With RAS-mutant Advanced Biliary Tract Cancer
- ClinicalTrials.gov ID
- NCT07908550
- Acronym / sponsor ID
- 111169
- Conditions
- Biliary Tract Cancer (BTC)
- Keywords
- RAS, second-line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Cancer Center, Japan, Kanagawa Cancer Center, National Cancer Center Hospital East, Taipei Veterans General Hospital, Taiwan, National Taiwan University Hospital, China Medical University Hospital, Taichung Veterans General Hospital, National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital
- Study start
- Jan 2027 (estimated)
- Primary completion
- Dec 2029 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 2 Nov 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial will assess the efficacy, safety, and tolerability of daraxonrasib monotherapy in Asian patients with RAS-mutated advanced biliary tract cancer in second-line treatment. The Primary Endpoint is Objective Response Rate (ORR).
Detailed description
After progression on first-line therapy, second-line treatment options for BTC remain limited, with standard regimens such as FOLFOX demonstrating modest efficacy (ORR ~5%, median OS 6.2 months) for those without druggable mutations. KRAS mutations are present in over 15% of BTC cases and are associated with poorer outcomes compared to KRAS wild-type. Daraxonrasib is a first-in-class multi-selective RAS(ON) inhibitor that has shown encouraging activity in KRAS-mutated cancers, including ORRs of 27-36% and median PFS up to 8.8 months in early-phase trials for metastatic pancreatic cancer, providing strong rationale to evaluate daraxonrasib in BTC.
The trial will assess the efficacy, safety, and tolerability of daraxonrasib monotherapy in patients with RAS-mutated advanced biliary tract cancer in second-line treatment.
- Primary Endpoint: Objective Response Rate (ORR).
- Secondary Endpoints: Progression-Free Survival (PFS); Overall Survival (OS); Duration of Response (DOR); Disease Control Rate (DCR); Adverse Event Profile (AEs); Quality of Life (QoL).
This is an open-label, single-arm study using Bayesian Optimal Phase II Design (N=55). Patients will be treated with daraxonrasib at 300 mg QD with continuous dosing in 28-day cycles. Competitive enrollment applies; however, a minimum of 6 patient slots is mandated for Japan. The trial tests a null hypothesis of a 5% response rate versus an alternative of 20%, with one-sided α < 0.05 and >90% power. An interim analysis occurs after 20 patients: if ≤1 response is observed, the trial stops for futility; if ≥2 responses are observed, enrollment continues to 55 patients. If ≥6 responses are observed among 55 patients, the treatment is considered promising. The interim decision is based on confirmed responses per RECIST v1.1. Enrollment continues while the interim analysis is pending so that the study timeline is preserved; only the first 20 patients contribute to the interim decision, and accrual during that period is capped at 16 additional patients (36 enrolled in total).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daraxonrasib | Experimental | Drug: Daraxonrasib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Age ≥ 18 years at the time of consent.
- Histologically or cytologically confirmed unresectable locally advanced and/or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, and carcinoma of the Ampulla of Vater, that has progressed or recurred after prior therapy.
- Documented pathogenic RAS (KRAS, NRAS, or HRAS) mutations confirmed by a CAP or CLIA-certified assay from tumor tissue or plasma.
- Progression or intolerance of first-line systemic chemotherapy lines (with or without immunotherapy) for unresectable and/or advanced stage disease. Prior systemic therapy administered in the adjuvant or neoadjuvant context may be considered as a prior line of therapy if disease recurrence or progression occurred during or within 6 months after the last dose of the systemic therapy.
- Radiographically measurable or evaluable disease per RECIST v1.1.
Key exclusion criteria (10 listed)
- Receipt of any systemic anti-cancer therapy for advanced BTC within 3 weeks of allocation/randomization or 5 half-lives of the drug (whichever is longer).
- Prior treatment with any RAS pathway inhibitor, including any KRAS, MEK, or receptor tyrosine kinase (RTK) inhibitor (or other RAS-pathway targeting agents).
- Concurrent use of strong CYP3A4 modulators or drugs that strongly inhibit/induce P-gp or BCRP, if alternatives are not feasible.
- Treatment with any of the following within the specified time frame prior to the first dose of study therapy, or failure to recover from side effects of these prior therapies:
- Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of study therapy).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DaraxonrasibDaraxonrasib 300 mg orally once daily | Drug | Daraxonrasib |
Primary outcome
Objective Response Rate (ORR)
Time frame: 2 years
ORR determined by the Investigator based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Each patient will be assigned a best overall response of one of the following RECIST categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE). A patient's best overall response will be determined from all tumor assessments performed from the date of treatment initiation until confirmed disease progression or study discontinuation for any reason, whichever occurs first.
6 secondary outcomes
Disease Control Rate (DCR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 3 years
Overall Survival (OS)
Time frame: 4 years
Duration of Response (DOR)
Time frame: 3 years
Safety Profile
Time frame: 2 years
Quality of Life (QoL)
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Results publication: PubMed 42223072O'Reilly EM, Wainberg ZA, Hendifar AE, Borad MJ, Pietrantonio F, Pant S, Hammel P, Cremolini C, Manji GA, Oberstein PE, Garrido-Laguna I, Springfeld C, Azad NS, Ueno M, Chui SY, Zhang Y, Patel H, Lee Y, Salman Z, Wolpin BM; RASolute 302 Trial Investigators. Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer. N Engl J Med. 2026 Jul 23;395(4):325-337. doi: 10.1056/NEJMoa2605555. Epub 2026 May 31.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Daraxonrasib in people with Biliary Tract Cancer (BTC), run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yung-Yeh Su, MD, PhD (886-6-7000123 ext. 65181, yysu@nhri.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07908550, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.