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

DualityBio

Status and phase: Enrolling; Phase 2

Conditions: Solid Tumors

Treatments: Drug: DB-1311/BNT324; Drug: BNT327; Drug: DB-1305/BNT325

Study type: Interventional

Funder types: Industry

Identifiers

NCT06953089

DB-1311-201

Details and patient eligibility

About

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

Full description

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) are eligible to participate in the trial.

Enrollment: 492 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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492 participants in 8 patient groups

Part 1 Cohort 1A, DB-1311/BNT324+ BNT327 combination therapy

Experimental group

Description:

Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D (Recommended Phase 2 Dose) and RP2D-1 in target population.

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324

Part 1 Cohort 2, DB-1311/BNT324+ DB-1305 /BNT325 combination therapy

Experimental group

Description:

Escalating combination dose levels of DB-1311/BNT324 and DB-1305/BNT325 to define RP2D and RP2D-1 in target population.

Treatment:

Drug: DB-1305/BNT325

Drug: DB-1311/BNT324

Part 2 Arm 1: RP2D of DB-1311/BNT324 + BNT327

Experimental group

Description:

In participants with unresectable advanced/metastatic HCC

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324

Part 2 Arm 2: RP2D of DB-1311/BNT324 + BNT327

Experimental group

Description:

In participants with unresectable advanced/ metastatic CC

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324

Part2 Arm 3:RP2D of DB-1311/BNT324 + BNT327

Experimental group

Description:

In participants with unresectable advanced/metastatic melanoma

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324

Part 2 Arm 4: RP2D of DB-1311/BNT324 + BNT327 and RP2D-1 of DB-1311/BNT324 + BNT327

Experimental group

Description:

In participants with recurrent/metastatic HNSCC

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324

Part 2 Arm 5: RP2D of DB-1311/BNT324 +DB-1305/BNT325 and RP2D-1 of DB-1311/BNT324 +DB-1305/BNT325

Experimental group

Description:

In participants with advanced/unresectable metastatic NSCLC

Treatment:

Drug: DB-1305/BNT325

Drug: DB-1311/BNT324

Part 1 Cohort 1B, DB-1311/BNT324+ BNT327 combination therapy

Experimental group

Description:

Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D and RP2D-1 in target population.

Treatment:

Drug: BNT327

Drug: DB-1311/BNT324