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

About

Brief Summary

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

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Key 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 CC with squamous cell, adenocarcinoma, or adenosquamous histology
- For Melanoma patients: Histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic/stage IV melanoma.
- For PROC patients (Part 1, Cohort 1A): 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 (Part 2 Arm 6 only): 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 (Part 2 Arm 7 only): Participants with advanced/unresectable metastatic PDAC without AGA who have progressed after only one prior line of standard systemic treatments (2L PDAC without AGA), or participants with AGA who have progressed on or after at least one and a maximum of two prior lines of standard systemic treatment (2L-3L PDAC with AGA).
- For breast cancer (Part 2 Arm 8 only):
  - 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 (Part 2 Arm 9 only): Participants with advanced/unresectable mCRC without AGA who have progressed after only one prior line of standard systemic treatment (2L mCRC without AGA), or participants with AGA who have progressed on or after at least one and a maximum of two prior lines of standard systemic treatment (2L-3L mCRC with AGA).
- For mCRPC (Part 2 Arm 10 only): Participants must have histologically or cytologically confirmed adenocarcinoma of the prostate and mCRPC

Key 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.