A Study to Select a Dose Regimen (Part A) and to Investigate Overall Survival (Part B) With Nanvuranlat Compared With Physician's Best Choice in Participants Aged 18 Years or Older With Biliary Tract Cancer

NCT07265674 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: JPH203-P3-BTC
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 18

Brief Summary

This study is designed to 1) select a dose regimen for continued development and 2) evaluate nanvuranlat versus Physicians Best Choice (PBC) (FOLFOX, FOLFIRI, or Best Supportive Care (BSC)) in participants aged 18 years and over with BTC. Participants enrolling in Part A the trial will be randomly assigned to receive 1 of 3 nanvuranlat dose regimens or PBC. In Part B, participants will be randomly assigned to receive nanvuranlat or PBC. Participants will receive treatment every 2 weeks for as long as they do not experience safety issues, or their cancer gets worse, and the study doctor feels they should stop treatment. Health measurements including physical examinations, vital signs, ECGs, and safety laboratory tests will be performed to monitor safety, and tumor imaging will be performed to monitor cancer response to treatment. Other exploratory makers will be measured to better understand how nanvuranlat works.

Conditions

Biliary Tract Cancer (BTC); Advanced Biliary Tract Cancer

Keywords

Intrahepatic cholangiocarcinoma (IHC); Extrahepatic cholangiocarcinoma (EHC); Gallbladder carcinoma (GBC)

Outcome Measures

Primary Outcomes (2)

• Part A: Preliminary Overall Survival (OS)

  OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.

  From date of first dose of study intervention until death [Approx. 24 months].

• Part B: Overall Survival

  OS is defined as the time from the date of Cycle 1 Day 1 to the date of death from any cause.

  From date of first dose of study intervention until death [Approx. 36 months]

Secondary Outcomes (6)

• Part B: Progression Free Survival

  From first dose of study intervention until disease progression or death (which ever occurs first) [Approx. 36 months].

• Part B: Objective Response Rate

  From first dose of study intervention until disease progression or death (which ever occurs first) [Approx. 36 months].

• Part B: Incidence of treatment-emergent adverse events (TEAEs)

  From first dose of study intervention and up to 30 days after last dose of study intervention [Approx. 36 months].

• Part B: Relative Dose Intensity

  From first dose of study intervention and up to first 8 weeks of treatment [Approx. 36 months].

• Part B: Dose Reductions, Interruptions and Discontinuations

  From first dose of study intervention through last dose of study drug intervention [Approx. 36 months].

Study Arms (4)

Nanvuranlat 50mg

EXPERIMENTAL

Nanvuranlat 50mg administered via a 90-minute intravenous infusion once daily for 5 consecutive days, followed by 9 days off treatment

Drug: Nanvuranlat

Navuranlat 75mg

EXPERIMENTAL

Nanvuranlat 75mg administered via a 90-minute intravenous infusion once daily for 5 consecutive days, followed by 9 days off treatment

Drug: Nanvuranlat

Navuranlat 375mg

EXPERIMENTAL

Nanvuranlat 375mg administered via a 46-hour continuous intravenous infusion once every 14 days

Drug: Nanvuranlat

Physicians Best Choice (PBC)

OTHER

1. FOLFOX regimen (Leucovorin, 5-Flurouracil and Oxaliplatin) administered on Day 1 of each 14 day cycle, or 2. FOLFIRI regimen (Leucovorin, 5-Flurouracil and Irinotecan) administered once during 14 day cycle, or 3. Best Supportive Care (BSC) including symptomatic therapeutics, palliative radiation for pre-existing metastases and transfusion of blood products administered at discretion of Investigator.

Other: Physician's Best Choice

Interventions

Physician's Best Choice OTHER

1. FOLFOX regimen (Leucovorin, 5-Flurouracil and Oxaliplatin) administered on Day 1 of each 14 day cycle, or 2. FOLFIRI regimen (Leucovorin, 5-Flurouracil and Irinotecan) administered once during 14 day cycle, or 3. Best Supportive Care (BSC) including symptomatic therapeutics, palliative radiation for pre-existing metastases and transfusion of blood products administered at discretion of Investigator.

Also known as: FOLFOX Regimen (Leucovorin, 5-Flurouracil and Oxaliplatin, FOLFIRI Regimen (Leucovorin, 5-Flurouracil and Irinotecan), Best Supportive Care (BSC)

Physicians Best Choice (PBC)

Nanvuranlat DRUG

Nanvuranlat, IV administration

Nanvuranlat 50mg; Navuranlat 375mg; Navuranlat 75mg

Eligibility Criteria

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

You may qualify if:

• \- Individuals are eligible to be included in the study only if all of the following criteria apply:
• At least 18 years of age inclusive at the time of signing the informed consent.
• Provides informed written consent according to local laws or regulations.
• Able and willing to comply with scheduled visits, treatment plans, procedures, and laboratory tests, including peripheral blood and urine sampling during the study.
• Willing to participate in LAT1 testing and NAT2 and transporter genotyping. Note: For LAT1 testing, if the participant does not have archival tissue and a fresh biopsy is not in the best interest of the participant, they will still be eligible for the trial.
• Cancer must be metastatic, locally advanced and unresectable, or not amenable to treatment with local therapies that could offer a reasonable likelihood of clinical benefit.
• Histologic or cytologic diagnosis of BTC.
• Has BTC that is classified as either an IHC, EHC, or GBC based on surgical, clinical, or laparoscopic findings and/or radiological imaging (eg, CT, MRI).
• Has received 1 prior appropriate platinum (cisplatin, carboplatin, or oxaliplatin)-based therapy for advanced disease (locally advanced or metastatic) with or without a mAb targeting PD-1 or PD-L1.
• Disease progression during or within 6 months of neoadjuvant or adjuvant treatment with a platinum-containing regimen will count as having received 1 prior regimen.
• If a patient has a mutation/fusion of IDH1, FGFR2 or NTRK, or an amplified, mutated, or overexpressed form of HER2, or a recognized aberration in a validated "driver" of BTC, and was treated with an appropriate targeted agent, or the patient's tumor was determined to be MSI-H and an appropriate PD-1/PD-L1 mAb was administered, the targeted therapy or immunotherapy will NOT count as a separate line of treatment.
• ECOG PS of 0 or 1.
• Expected life expectancy of at least 90 days after the first day of treatment as per the site Investigator.
• At least 1 measurable lesion by RECIST v1.1 based on imaging (eg, CT, MRI) performed within 28 days prior to initiation of study intervention. Those who have received prior local therapy, including but not limited to embolization, chemoembolization, radiation therapy, and/or other appropriate ablative procedures to a measurable lesion that is within the treatment and shown ≥ 20% growth in size since posttreatment assessment.
• Resolution to ≤ Grade 1 by the NCI CTCAE v 5.0 (or higher) of all clinically significant toxic effects of prior chemotherapy or other treatments, except for alopecia and peripheral neuropathy (these must have resolved to ≤ Grade 2). If medical therapy is required for the treatment of a laboratory abnormality, the dose and laboratory value(s) should be stable.

You may not qualify if:

• Individuals will be excluded from study participation if they meet any of the following criteria:
• Received systemic therapy or an investigational agent before washing out, as follows:
• \< 2 weeks prior to Cycle 1 Day 1 for systemic non-immune-based therapy
• \< 3 weeks prior to Cycle 1 Day 1 for immune-based therapy
• ≤ 5 half-lives or 3 weeks (whichever is longer) prior to Cycle 1 Day 1 for an investigational agent
• Received radiotherapy to metastatic sites within 2 weeks of Cycle 1 Day 1. Patients must have recovered from all radiation-related toxicities and not require corticosteroids. A 1 week washout is permitted for palliative radiation with a limited port ≤ 2 weeks of radiotherapy to non-CNS disease.
• Underwent hepatic radiation, chemoembolization, or radiofrequency ablation \< 4 weeks prior to Cycle 1 Day 1.
• Underwent major surgery \< 3 weeks before Screening and has not recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention.
• Known active CNS metastases and/or carcinomatous meningitis. Those with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of PD for at least 4 weeks by repeat imaging), clinically stable, and without requirement of corticosteroid treatment for at least 14 days prior to first dose of study intervention. For those with a history of CNS involvement, repeat imaging should be performed during study screening. However, CNS imaging is not required prior to study entry unless there is clinical suspicion of CNS involvement.
• Clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Resting QTcF \> 470 msec at screening.
• An additional active malignancy that is progressing or has required active treatment within the past 3 years. Cases involving a past cancer history with substantial potential for recurrence must be discussed with the Medical Monitor before study entry. Patients with the following concomitant neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including transitional cell carcinoma, cervical intraepithelial neoplasia, breast cancer, and melanoma in situ), organ-confined prostate cancer with no evidence of PD.
• Require strong inhibitors of P-gp, BCRP, OATP1B1, OATP1B3, OATP1A2, and OAT3 transporters unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Require sensitive substrates of OATP1B1 and OATP1B3 unless they can be transferred to other medications within ≥ 5 half-lives of treatment.
• Known positive status for HIV, has not been treated with established appropriate antiretroviral therapy for at least 4 weeks, and has a hydrophobic interaction chromatography viral load \< 400 copies/mL and a CD4+ T-cell (CD4+) counts ≥ 350 cells/µL prior to enrollment. No HIV testing is required unless mandated by local health authority.

Sponsors & Collaborators

• J-Pharma Co., Ltd.: lead
• Uniphar Development, LLC: collaborator

Study Sites (18)

Banner MD Anderson Cancer Center (Site 106)

Gilbert, Arizona, 85234, United States

NOT YET RECRUITING

City of Hope (Site 107)

Duarte, California, 91010, United States

NOT YET RECRUITING

University of California at Irvine (Site 101)

Orange, California, 92868, United States

NOT YET RECRUITING

UCLA Medical Center (Site 117)

Santa Monica, California, 90404, United States

NOT YET RECRUITING

Norton Cancer Institute (Site 115)

Louisville, Kentucky, 40127, United States

NOT YET RECRUITING

Ochsner Medical Center (Site 120)

New Orleans, Louisiana, 70121, United States

NOT YET RECRUITING

Henry Ford Cancer Center (Site 113)

Detroit, Michigan, 48186, United States

NOT YET RECRUITING

Karmanos Cancer Center (Site 109)

Detroit, Michigan, 48201, United States

NOT YET RECRUITING

Masonic Cancer Center, University of Minnesota (Site 116)

Minneapolis, Minnesota, 55455, United States

NOT YET RECRUITING

Rutgers Cancer Institute of New Jersey (Site 103)

New Brunswick, New Jersey, 08901, United States

RECRUITING

Rosewell Park Comprehensive Cancer Center (Site 114)

Buffalo, New York, 14263, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center (Site 108)

New York, New York, 10065, United States

NOT YET RECRUITING

University Hospitals Cleveland Medical Center Seidman Cancer Center (Site 111)

Cleveland, Ohio, 44106, United States

RECRUITING

James Cancer Hospital and Solove Research Institute (Site 119)

Columbus, Ohio, 43219, United States

NOT YET RECRUITING

Mercy Clinic (Site 110)

Oklahoma City, Oklahoma, 73120, United States

RECRUITING

Allegheny Health Network (Site 121)

Pittsburgh, Pennsylvania, 15212, United States

NOT YET RECRUITING

University of Texas Southwestern Medical Center (Site 104)

Dallas, Texas, 75390, United States

NOT YET RECRUITING

University of Texas MD Anderson Cancer Center (Site 102)

Hosuton, Texas, 77030, United States

NOT YET RECRUITING

Related Publications (1)

• Furuse J, Ikeda M, Ueno M, Furukawa M, Morizane C, Takehara T, Nishina T, Todaka A, Okano N, Hara K, Nakai Y, Ohkawa K, Sasaki T, Sugimori K, Yokoyama N, Yamamoto K. A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy. Clin Cancer Res. 2024 Sep 13;30(18):3990-3995. doi: 10.1158/1078-0432.CCR-24-0461.

  PMID: 39058429 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms

Interventions

Folfox protocol; Leucovorin; Oxaliplatin; Irinotecan

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids

Study Officials

• Eric K Rowinsky, MD

  Uniphar Development, LLC

  STUDY DIRECTOR

• Ghassan Abou-Alfa, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Masuhiro Yoshitake

CONTACT

+81-3-6432-4270; BeaconBTC@uniphar.us

Kazuo Sekiguchi

CONTACT

+81-3-6432-4270; BeaconBTC@uniphar.us

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2025
• First Posted: December 5, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (18)