Clinical trial NCT06953089: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Solid Tumors
Keywords: B7-H3
PD-L1/VEGF-A
TROP2
ADC
HNSCC
HCC
CC
Melanoma
NSCLC
Lead sponsor: DualityBio Inc.
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2025-05-01
Enrollment: 440
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

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:

* 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.

Primary outcomes:
measure: Part 1: Number of participants with Dose Limiting Toxicities (DLTs).
timeFrame: During the DLT evaluation period, i.e., the time of initiation of the first dose of investigational medicinal product (IMP) up to 21 days
measure: Part 1 and Part 2: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs)
timeFrame: 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
measure: 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).
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
Secondary outcomes:
measure: 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).
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Duration of response (DoR) per RECIST 1.1 based on the investigator's assessment.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Overall survival (OS)
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with BNT327.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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).
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Disease-control rate (DCR) per RECIST 1.1 based on the investigator's assessment.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Time to response (TTR) per RECIST 1.1 based on the investigator's assessment.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Progression-free survival (PFS) per RECIST 1.1 based on the investigator's assessment.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and Part 2: ADA incidence: the proportion of participants having treatment-emergent ADA.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: Part 1 and 2: Maximum observed concentration (Cmax) of DB-1311/BNT324 ADC, total antibody and unconjugated P1021 in combination with DB-1305/BNT325.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
measure: 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.
timeFrame: From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Research Site USA04-0
state: New York
city: Charleston
country: United States
facility: Research Site USA03-0
state: South Carolina
city: North Ryde BC
country: Australia
facility: Research Site AUS02-0
state: New South Wales
city: Hefei
country: China
facility: Research Site CHN09-0
state: Anhui
city: Beijing
country: China
facility: Research Site CHN02-0
state: Beijing
city: Beijing
country: China
facility: Research Site CHN03-0
state: Beijing
city: Harbin
country: China
facility: Research Site CHN08-0
state: Heilongjiang
city: Zhengzhou
country: China
facility: Research Site CHN06-0
state: Henan
city: Wuhan
country: China
facility: Research Site CHN05-0
state: Hubei
city: Nanchang
country: China
facility: Research Site CHN07-0
state: Jiangxi
city: Shanghai
country: China
facility: Research Site CHN04-0
state: Shanghai
city: Shanghai
country: China
facility: Research Site CHN10-0
state: Shanghai
city: New Taipei City
country: Taiwan
facility: Research Site TWN02-0
state: Taipei
city: Taipei City
country: Taiwan
facility: Research Site TWN03-0
state: Taipei
city: Taipei City
country: Taiwan
facility: Research Site TWN01-0
state: Taipei
Study officials:
References: