A PHASE 1, MULTICENTER, OPEN-LABEL STUDY EVALUATING THE SAFETY AND TOLERABILITY OF NANVURANLAT ADMINISTERED AS A 46-HOUR CONTINUOUS INTRAVENOUS INFUSION, WITH OR WITHOUT DURVALUMAB, IN PATIENTS WITH UNRESECTABLE OR RECURRENT BILIARY TRACT CANCER
A PHASE 1, MULTICENTER, OPEN-LABEL STUDY EVALUATING THE SAFETY AND TOLERABILITY OF NANVURANLAT ADMINISTERED AS A 46-HOUR CONTINUOUS INTRAVENOUS INFUSION, WITH OR WITHOUT DURVALUMAB, IN PATIENTS WITH UNRESECTABLE OR RECURRENT BILIARY TRACT CANCER
Ozaka Masato
Cancer Institute Hospital of JFCR
3-8-31 Ariake, Koto-ku, Tokyo
+81-3-3520-0111
masato.ozaka@jfcr.or.jp
Ozaka Masato
Cancer Institute Hospital of JFCR
3-8-31 Ariake, Koto-ku, Tokyo
+81-3-3520-0111
masato.ozaka@jfcr.or.jp
Recruiting
May. 01, 2026
24
Interventional
single arm study
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1.Written informed consent has been obtained from the patient prior to participation in this study.
2.Age >= 18 years at the time of obtaining informed consent.
3.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4.Diagnosis of unresectable or recurrent biliary tract cancer, including extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma, or gallbladder cancer, confirmed by contrast-enhanced CT or MRI of the chest, abdomen, and pelvis.
5.Histologically or cytologically confirmed adenocarcinoma as the predominant histological subtype.
Patients with cytology classified as Class IV or histology classified as Group 4 are eligible provided that histological subtypes other than adenocarcinoma or adenosquamous carcinoma are not suspected.
6.Adequate organ function as demonstrated by clinical laboratory tests performed within 14 days prior to enrollment, meeting all of the following criteria:
-Hemoglobin >= 9.0 g/dL
-Platelet count >= 75,000 /mm3
-Absolute neutrophil count >= 1,500 /mm3
-AST and ALT <= 2.5 x upper limit of normal (ULN)
(<= 5 x ULN in patients with liver metastases or those who have undergone biliary drainage)
-Total bilirubin <= 1.5 x ULN
-Serum creatinine <= 1.5 x ULN
7.An estimated life expectancy of at least 90 days, as judged by the investigator.
8.For male patients and women of childbearing potential, agreement to use adequate contraception from the time of informed consent through 90 days after the final dose of the investigational product, and to refrain from sperm or oocyte donation (including collection of sperm or oocytes for personal future use) and from breastfeeding during this period.
-Women of childbearing potential are defined as women who have experienced menarche and have not undergone surgical sterilization (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) and are not postmenopausal. Postmenopause is defined as amenorrhea for at least 12 consecutive months without an alternative medical cause.
-Acceptable methods of contraception include oral contraceptives, condoms, and intrauterine devices.
-For female patients, contraception by the male partner is acceptable. Male patients with reproductive potential must use condoms unless they have undergone a confirmed vasectomy.
Additional Inclusion Criteria for Part A Only
9.Patients who have experienced disease progression following second-line or later systemic therapy, including gemcitabine-containing standard chemotherapy, for advanced biliary tract cancer.
Additional Inclusion Criteria for Part B Only
10.Patients who have received 6 to 8 cycles of first-line gemcitabine, cisplatin, and durvalumab (GCD) therapy without evidence of disease progression and are scheduled to receive durvalumab maintenance therapy.
Patients who discontinued cisplatin during GCD therapy are eligible.
Combination with gemcitabine plus pembrolizumab maintenance therapy is not permitted in this study.
11.Absence of actionable molecular alterations, including MSI-high, dMMR, TMB-high, FGFR fusion, IDH1 mutation, or HER2 amplification.
1)Evidence of central nervous system metastases based on clinical evaluation or imaging studies.
2)Presence of clinically significant ascites, pleural effusion, or pericardial effusion requiring drainage, defined as moderate or greater fluid accumulation extending beyond the pelvic cavity to the anterior surface of the liver on CT imaging.
3)Presence of active multiple primary malignancies, defined as synchronous multiple cancers or metachronous multiple cancers with a disease-free interval of less than 2 years that require active treatment.
4)Presence of an active autoimmune disease or a history of severe autoimmune disease.
Patients with conditions such as vitiligo or autoimmune hypothyroidism adequately controlled with hormone replacement therapy may be eligible if, in the investigator's judgment, the condition does not interfere with study participation.
5)Presence or history of interstitial lung disease, including radiation-induced pneumonitis.
6)Presence or history of active inflammatory bowel disease, including conditions associated with bloody diarrhea, frequent diarrhea, or watery stools.
7)History of allogeneic organ transplantation.
8)Ongoing systemic corticosteroid therapy exceeding a prednisone-equivalent dose of 10 mg/day, excluding topical or inhaled corticosteroids.
9)History of shock, anaphylaxis, or renal impairment attributable to sulfobutylether-beta-cyclodextrin (SBECD) or other excipients contained in the investigational product.
10)Presence or history of serious or clinically significant comorbidities, as judged by the investigator or sub-investigator, including but not limited to:
-(a) Severe cardiovascular or cerebrovascular disorders, such as cerebrovascular disease, pulmonary embolism, ischemic heart disease, arrhythmia, myocardial infarction, or heart failure (excluding malignant diseases)
-(b) Psychiatric disorders
-(c) Drug dependence or alcohol dependence
-(d) Any other condition that may compromise patient safety, informed consent, or compliance with the study protocol
11)Presence of clinically significant electrocardiogram abnormalities.
12)Prior radiation therapy involving more than one-third of the bone marrow.
13)Presence of an active infection requiring systemic treatment.
14)Positive test results for HIV-1 antibody, hepatitis B surface antigen (HBsAg), or hepatitis C virus RNA (HCV-RNA).
15)Pregnant or breastfeeding women, or women with suspected pregnancy at the time of enrollment.
For premenopausal women and women within one year after menopause, a negative pregnancy test must be confirmed prior to enrollment. Menopause is defined as amenorrhea for at least 12 consecutive months without an alternative medical cause.
16)Any patient deemed inappropriate for participation in this study by the investigator or sub-investigator
18age old over
No limit
Both
Unresectable or Recurrent Biliary Tract Cancer
Part A
Nanvuranlat 375mg will be administered as monotherapy as a 46-hour continuous intravenous infusion. This administration will be repeated every 2 weeks, with one treatment cycle defined as 14 days.
Part B
Durvalumab: 1500 mg administered intravenously every 4 weeks.
Nanvuranlat: 375mg administered as a 46-hour continuous intravenous infusion, repeated every 2 weeks.
Type and incidence of dose-limiting toxicities (DLTs)
- Type and incidence of adverse events (AEs)
- Progression-free survival (PFS)
- Objective response rate (ORR)
- Disease control rate (DCR)
- Tumor markers
- Overall survival (OS)
- Pharmacokinetics (PK) in blood
- Association between LAT1 score and treatment efficacy
J-Pharma Co., Ltd.
Not applicable
The Cancer Institute Hospital of JFCR Institutional Review Board
