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

Official title

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

Overview

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

Detailed 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), 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.

Interventions

• Drug DB-1311/BNT324
  Administered I.V.
• Drug BNT327
  Administered I.V.
• Drug DB-1305/BNT325
  Administered I.V.

Primary outcome measures

• Part 1: Number of participants with Dose Limiting Toxicities (DLTs). [Time frame: During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days]
• Part 1: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) [Time frame: up to follow up period, e.g. up to 72 months.]
• Part 2: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) [By arm and dose level] [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 2: Objective response rate (ORR), defined as the proportion of participants in whom a confirmed Complete response (CR) or PR is observed as best overall response (per RECIST 1.1 based on the investigator's assessment)by arm and dose level. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]

Secondary outcome measures (12)

• Part 1: ORR, defined as the proportion of participants in whom a confirmed CR or PR is observed as best overall response (per RECIST 1.1 based on the investigator's assessment). [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Duration of response (DoR) per RECIST 1.1 based on the investigator's assessment. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Overall survival (OS) [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Disease-control rate (DCR) per RECIST 1.1 based on the investigator's assessment. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Time to response (TTR) per RECIST 1.1 based on the investigator's assessment. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Progression-free survival (PFS) per RECIST 1.1 based on the investigator's assessment. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1: Cancer antigen 125 (CA-125) response rate assessed per Gynecological Cancer Intergroup (GCIG) criteria in participants with platinum-resistant ovarian cancer (PROC). [Time frame: From the time of initiation of the first dose of IMP to end of Part 1]
• Part 1: Cancer antigen 125 (CA-125) response rate assessed per Gynecological Cancer Intergroup (GCIG) criteria in participants with PROC. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 2:Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]
• Part 1 and 2: Time to reach maximum observed concentration (Tmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327. [Time frame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 16 centers

• CHN02-0 — Beijing
• CHN13-0 — Beijing
• CHN23-0 — Beijing
• CHN17-0 — Dongguan
• CHN06-0 — Henan
• CHN12-0 — Xinxiang
• CHN04-0 — Hubei
• CHN26-0 — Wuhan
• … and 8 more centers

United States · 15 centers

• USA06-0 — Los Angeles
• USA16-0 — Los Angeles
• USA01-0 — Wheat Ridge
• USA08-0 — Florida City
• USA10-0 — Atlanta
• USA11-0 — Bethesda
• USA14-0 — Lincoln
• USA04-0 — New York
• … and 7 more centers

Australia · 4 centers

• AUS07-0 — North Sydney
• AUS06-0 — Benowa
• AUS04-0 — Birtinya
• AUS05-0 — Adelaide

Taiwan · 2 centers

• TWN01-0 — Taipei
• TWN02-0 — Taipei

Identifiers

NCT: NCT06953089 · DB-1311-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗