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

Phase 2RecruitingNCT06953089

DualityBio Inc.492 enrolled

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

492

Conditions

Solid Tumors

Interventions

DB-1311/BNT324DRUG

Administered I.V.

BNT327DRUG

Administered I.V.

DB-1305/BNT325DRUG

Administered I.V.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (37)

Outcomes

Primary Outcomes

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 Outcomes

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

Central Contacts

Jay Ma

CONTACT

540-808-3925 jay.ma@dualitybiologics.com

Qiaoli Jiang

CONTACT

+86-15210642683 qiaoli.jiang@dualitybiologics.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

USA06-0

Los Angeles, California, United States

RECRUITING

USA16-0

Los Angeles, California, United States

RECRUITING

USA01-0

Wheat Ridge, Colorado, United States

RECRUITING

USA08-0

Florida City, Florida, United States

RECRUITING

USA10-0

Atlanta, Georgia, United States

RECRUITING

USA11-0

Bethesda, Maryland, United States

RECRUITING

USA14-0

Lincoln, Nebraska, United States

RECRUITING

USA04-0

New York, New York, United States

RECRUITING

USA15-0

Portland, Oregon, United States

RECRUITING

USA03-0

Charleston, South Carolina, United States

RECRUITING

...and 27 more locations

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