D07001 Softgel-Capsules and Capecitabine Combination Therapy in Patients With Advanced Biliary Tract Cancer

The object of this trial is to evaluate the efficacy of D07001-softgel capsules + capecitabine compared with placebo + capecitabine by overall survival (OS). Eligible patients with advanced biliary tract cancer (BTC) will be randomized (1:1:1) to receive either 60 mg D07001-softgel, 100 mg D07001-softgel, or placebo, combine with capecitabine. Treatment will be continued until disease progression, death, withdraw consent, or completing 12 treatment cycles , whichever occurs first.

Inclusion Criteria: 1. Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements. 2. Participant aged at least 18 years at the time of consent. 3. Participant has histopathological or cytologic diagnosis of unresectable, locally advanced or metastatic BTC (cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma). 4. Participant has measurable disease as assessed by central review by RECIST v1.1. 5. Participant must have failed on a gemcitabine + cisplatin-based chemotherapy, regardless of whether an immune checkpoint inhibitor, such as durvalumab or pembrolizumab, or S-1 (tegafur, gimeracil, and oteracil potassium), was also administered. Oxaliplatin or carboplatin may be substituted for cisplatin when renal or auditory function is of concern. Participants also have failed (disease progression or intolerance) on, or refused FOLFOX chemotherapy, including modified FOLFOX variants, or failed on irinotecan + fluorouracil-based chemotherapy. 6. Participants with tumors expressing the following biomarkers may be enrolled even if they have not previously received FOLFOX but have received appropriate targeted therapies until disease progression or intolerance: fibroblast growth factor receptors (FGFR) aberrations, microsatellite instability biomarker/deficient DNA mismatch repair, Tumor Mutation Burden-high, or mutations in isocitrate dehydrogenase, BRAF, HER2, NTRK, RET, or KRAS G12C. 7. Participant has ECOG PS of 0-2. 8. Participant's life expectancy is ≥12 weeks. 9. Participant has adequate bone marrow function, demonstrated by: 1. Absolute neutrophil count ≥1500 cell/mm3. 2. Platelet count ≥85,000 cells/mm3. 3. Hemoglobin ≥9 g/dL. 10. Participant has adequate liver function, demonstrated by: 1. Aspartate transaminase and alanine transaminase ≤2.5 × upper limit of normal (ULN), or ≤5.0 × ULN in the case of liver lesions. 2. Total bilirubin ≤1.5 × ULN. 3. Albumin ≥3.0 g/dL. 4. International normalized ratio \45 years, in the absence of hormone replacement therapy. If necessary, a blood sample for follicle stimulating hormone will be obtained to confirm postmenopausal status. 2. A participant of CBP who is sexually active with a partner who could impregnate them agrees to use a highly effective form of contraception during the study and for at least 6 months after the EOS intervention. 14. Participants with partners of childbearing potential whom they could impregnate must agree to use contraception during the study and for 3 months after the EOS intervention. 15. Participants who are able to donate sperm must refrain from sperm donation during the study and for 3 months after the EOS intervention. 16. Participant is willing to comply with the protocol-required visit schedule and visit requirements. 17. More than 14 days have elapsed between the participant completing a prior line of chemotherapy or targeted therapy, and enrollment. More than 28 days have elapsed between the participant receiving concurrent radiotherapy (CCRT) and enrollment Exclusion Criteria: 1. Participant has a diagnosis of active malignancy other than BTC within the past 2 years, except nonmelanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent. 2. Participant discontinued prior gemcitabine due to pulmonary or hepatic toxicity or hemolytic uremic syndrome, hypersensitivity, allergic reaction, or intolerance. 3. Participant had a prior unanticipated severe reaction to capecitabine or metabolites or to fluoropyrimidine therapy. 4. Participant received treatment with brivudine, sorivudine, or its chemically related analogs ≤28 days prior to the date of enrollment. 5. Participant is currently receiving flucytosine treatment. 6. Participant has residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2 neuropathy and alopecia are permitted). 7. Participant has any gastrointestinal disorder or prior gastrointestinal surgery that would significantly impede absorption of an oral agent, such as gastrectomy, Crohn's disease, ulcerative colitis, or short gut syndrome. 8. Participant has known brain or leptomeningeal metastases. 9. Participant had major surgery or definitive ablation-intent (excluding palliative radiotherapy for bone metastasis) radiation therapy within the past 28 days. 10. Participant has any active disease or condition that would not permit compliance with the protocol. 11. Participant has clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, congestive heart failure, New York Heart Association Grade 2 or greater), or uncontrolled serious cardiac arrhythmia. 12. Participant has documented cerebrovascular disease. 13. Participant has a seizure disorder not controlled with medication (based on Investigator's decision). 14. Participant has received an investigational agent within 28 days of enrollment. 15. Participant has an uncontrolled active viral, bacterial, or systemic fungal infection. 16. Participants with positive hepatitis B surface antigen (HBsAg) or positive hepatitis C virus antibody (anti-HCV) and detectable hepatitis B virus (HBV) DNA ≥2000 copies/mL or hepatitis C virus (HCV) RNA above the institutional lower limit of quantification are excluded. Participants with resolved HBV infection (negative HBsAg and positive hepatitis B core antibody \[anti-HBc\]) are eligible if HBV DNA is \