DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors

A Phase II, Multicenter, Open-Label Trial of DB-1311 in Combination With BNT327 or DB-1305 in Participants With Advanced/Metastatic Solid Tumors

A Phase II, Multicenter, Open-Label Trial of DB-1311 in combination with BNT327 or DB-1305 in Participants with Advanced/Metastatic Solid Tumors

This is a phase II, multicenter, open-label, two-part trial designed to evaluate the safety and preliminary efficacy of DB-1311 in combination with BNT327 or DB-1311 in combination with DB-1305 in targeted participants.

Participants with recurrent, progressive as well as advanced, metastatic hepatocellular carcinoma (HCC), cervical cancer (CC), melanoma, head and neck squamous cell carcinoma (HNSCC), platinum-resistant ovarian cancer (PROC) or non-small cell lung cancer (NSCLC), platinum-sensitive ovarian cancer (PSOC), pancreatic ductal carcinoma (PDAC), breast cancer, colorectal cancer (CRC), or metastatic castration resistant prostate cancer (mCRPC) are eligible to participate in the trial.

Inclusion Criteria:

• Adults aged ≥ 18 years or acceptable age according to local regulations at the time of voluntarily signing informed consent.

• At least one measurable lesion as assessed by the Investigator according to RECIST v1.1 criteria.

• Has a life expectancy of ≥ 3 months.

• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

• Has adequate organ function within 7 days prior to enrollment/randomization,

• Has adequate treatment washout period prior to the first dose of trial treatment.

  • For HCC patients: Histological/cytological confirmed diagnosis of HCC or clinically confirmed diagnosis of HCC; Has a Child-Pugh class A liver score.

  • For CC patients: Has persistent, recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology

  • For Melanoma patients: Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic melanoma.

  • For PROC patients (Cohort A): Participants must have a confirmed diagnosis of OC, primary peritoneal cancer, or fallopian tube cancer, all of which with high-grade serous histology. Patients must have platinum-resistant disease.

  • For HNSCC patients: Histologically or cytologically confirmed recurrent (recurrent disease that is not amendable to curative treatment with local/ or systemic therapies)/ (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies.

  • For NSCLC patients: Pathologically documented Stage IIIB or IIIC NSCLC not amenable for radical surgery or definitive chemoradiation or Stage IV NSQ NSCLC. Not harboring an EGFR-sensitizing mutation or ALK gene rearrangements or other onco-driver gene mutations

  • For PSOC: Must have PSOC, defined as radiographically documented disease recurrence or progression occurring >6 months after completion of the last dose of platinum-based chemotherapy.

  • For PDAC: Participants must have histologically or cytologically confirmed metastatic PDAC., who have progressed after at least one prior line of standard systemic treatment ((≥2L PDAC).)

  • For breast cancer:

    • HR+/HER2-low or HR+/HER2-ultralow or HR+/HER2-negative BC participants: Pathologically or cytologically documented HR-positive unresectable or metastatic BC with HER2-low, HER2-ultralow or HER2-negative expression.
    • Triple negative breast cancer (TNBC): Pathologically or cytologically documented unresectable or metastatic TNBC

  • For mCRC: Participants who have metastatic CRC and have relapsed or progressed after 1 prior line of systemic treatment including a fluoropyrimidine plus oxaliplatin with or without anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) or anti-epidermal growth factor receptor mAb therapy, as clinically indicated, or have relapsed or progressed after 2 lines of therapy if the participant has received targeted therapy

  • For mCRPC: Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and mCRPC

Exclusion Criteria:

• 1. Prior treatment with B7H3 targeted therapy.
• Prior treatment with antibody-drug conjugate with topoisomerase inhibitor.
• Is a candidate to locoregional treatment with potential to induce complete or near complete response and prolonged tumor control, per investigator's assessment.
• Has an uncontrolled concomitant or intercurrent illness, that in the opinion of the investigator, contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring AEs.
• Has uncontrolled or significant cardiovascular disease. Has clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt, or cell-free concentrated ascites reinfusion therapy.
• Has a history of (non-infectious) ILD/pneumonitis.
• Any autoimmune, connective tissue or inflammatory disorders.
• Has spinal cord compression or clinically active central nervous system (CNS) metastases.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline.