DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors
Phase 2
Not yet recruiting
- Conditions
- Solid Tumors
- Interventions
- Registration Number
- NCT06953089
- Lead Sponsor
- DualityBio Inc.
- 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
- 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) or non-small cell lung cancer (NSCLC) are eligible to participate in the trial.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 440
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.
Exclusion Criteria
- 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.
Exclusion Criteria:
-
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 Cohort 1, DB-1311/BNT324+ BNT327 combination therapy DB-1311/BNT324 Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D and RP2D-1 in target population. Part 1 Cohort 2, DB-1311/BNT324+ DB-1305 /BNT325 combination therapy DB-1305/BNT325 Escalating combination dose levels of DB-1311/BNT324 and DB-1305/BNT325 to define RP2D and RP2D-1 in target population. Part 2 Arm 1: RP2D of DB-1311/BNT324 + BNT327 BNT327 In participants with unresectable advanced/metastatic HCC Part 1 Cohort 1, DB-1311/BNT324+ BNT327 combination therapy BNT327 Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D and RP2D-1 in target population. Part 1 Cohort 2, DB-1311/BNT324+ DB-1305 /BNT325 combination therapy DB-1311/BNT324 Escalating combination dose levels of DB-1311/BNT324 and DB-1305/BNT325 to define RP2D and RP2D-1 in target population. Part 2 Arm 1: RP2D of DB-1311/BNT324 + BNT327 DB-1311/BNT324 In participants with unresectable advanced/metastatic HCC Part 2 Arm 2: RP2D of DB-1311/BNT324 + BNT327 DB-1311/BNT324 In participants with unresectable advanced/ metastatic cervical cancer (CC) Part 2 Arm 2: RP2D of DB-1311/BNT324 + BNT327 BNT327 In participants with unresectable advanced/ metastatic cervical cancer (CC) Part 2 Arm 4: RP2D of DB-1311/BNT324 + BNT327 and RP2D-1 of DB-1311/BNT324 + BNT327 DB-1311/BNT324 In participants with recurrent/metastatic HNSCC Part 2 Arm 4: RP2D of DB-1311/BNT324 + BNT327 and RP2D-1 of DB-1311/BNT324 + BNT327 BNT327 In participants with recurrent/metastatic HNSCC Part2 Arm 3:RP2D of DB-1311/BNT324 + BNT327 DB-1311/BNT324 In participants with unresectable advanced/metastatic melanoma Part2 Arm 3:RP2D of DB-1311/BNT324 + BNT327 BNT327 In participants with unresectable advanced/metastatic melanoma Part 2 Arm 5: RP2D of DB-1311/BNT324 +DB-1305/BNT325 and RP2D-1 of DB-1311/BNT324 +DB-1305/BNT325 DB-1311/BNT324 In participants with advanced/unresectable metastatic NSCLC Part 2 Arm 5: RP2D of DB-1311/BNT324 +DB-1305/BNT325 and RP2D-1 of DB-1311/BNT324 +DB-1305/BNT325 DB-1305/BNT325 In participants with advanced/unresectable metastatic NSCLC
- Primary Outcome Measures
Name Time Method Part 1: Number of participants with Dose Limiting Toxicities (DLTs). 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 and Part 2: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs) From the time of the first dose of IMP to 90 days after the last IMP dose (For BNT327 Combo) or 30 days after last dose (For DB-1305/BNT325 Combo) or until new anticancer therapy is started, whichever occurs first 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). From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
- Secondary Outcome Measures
Name Time Method Part 1 and 2: Time to response (TTR) per RECIST 1.1 based on the investigator's assessment. 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. 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. From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months Part 1: Objective response rate (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). 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. 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) 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. 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). 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. 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. 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. 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. 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. 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. 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. 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. From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
Trial Locations
- Locations (15)
Research Site TWN01-0
🇨🇳Taipei City, Taipei, Taiwan
Research Site USA04-0
🇺🇸New York, New York, United States
Research Site USA03-0
🇺🇸Charleston, South Carolina, United States
Research Site AUS02-0
🇦🇺North Ryde BC, New South Wales, Australia
Research Site CHN09-0
🇨🇳Hefei, Anhui, China
Research Site CHN02-0
🇨🇳Beijing, Beijing, China
Research Site CHN03-0
🇨🇳Beijing, Beijing, China
Research Site CHN08-0
🇨🇳Harbin, Heilongjiang, China
Research Site CHN06-0
🇨🇳Zhengzhou, Henan, China
Research Site CHN05-0
🇨🇳Wuhan, Hubei, China
Research Site CHN07-0
🇨🇳Nanchang, Jiangxi, China
Research Site CHN04-0
🇨🇳Shanghai, Shanghai, China
Research Site CHN10-0
🇨🇳Shanghai, Shanghai, China
Research Site TWN02-0
🇨🇳New Taipei City, Taipei, Taiwan
Research Site TWN03-0
🇨🇳Taipei City, Taipei, Taiwan