A Phase II, Multicenter, Open-Label Trial of DB-1311 in Combination With BNT327 or DB-1305 in Participants With Advanced/Metastatic Solid Tumors
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
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.
Arms & interventions
- DrugDB-1311/BNT324
Administered I.V.
- DrugBNT327
Administered I.V.
- DrugDB-1305/BNT325
Administered I.V.
Outcome measures
Primary
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
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
Part 1 and 2: Time to reach maximum observed concentration (Tmax) 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: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf) 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: Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf) 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: Terminal elimination half-life (t1/2) of DB-1311/BNT324 total 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: Terminal elimination half-life (t1/2) 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: Anti-drug antibody (ADA) prevalence: the proportion of participants who are ADA positive at any point in time (at baseline and post-baseline).
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 Part 2: ADA incidence: the proportion of participants having treatment-emergent ADA.
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
Study locations (15)
USA06-0
Los Angeles, California, 90025
USA16-0
Los Angeles, California, 90025
USA01-0
Wheat Ridge, Colorado, 80033
USA08-0
Florida City, Florida, 99208
USA10-0
Atlanta, Georgia, 30318
USA11-0
Bethesda, Maryland, 20817
USA14-0
Lincoln, Nebraska, 68506
USA04-0
New York, New York, 10032
USA15-0
Portland, Oregon, 97239
USA03-0
Charleston, South Carolina, 29425
USA13-0
Anderson, Texas, 46011
USA12-0
Houston, Texas, 77030
USA05-0
Virginia Beach, Virginia, 22031
USA09-0
Puyallup, Washington, 98373
USA07-0
Spokane, Washington, 99208