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

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

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 Overview

• Status: Recruiting
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: BNT327; Drug: DB-1311/BNT324; Drug: DB-1305/BNT325

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.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qiaoli Jiang; Phone Number: +86-15210642683; Email: qiaoli.jiang@dualitybiologics.com
• Study Contact Backup: Name: Jay Ma; Phone Number: 540-808-3925; Email: jay.ma@dualitybiologics.com

Study Locations

• Australia
  • New South Wales
    • North Sydney, New South Wales, Australia, 2060
      • Recruiting
      • AUS07-0
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • AUS06-0
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • AUS04-0
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • AUS05-0
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • CHN02-0
    • Beijing, Beijing Municipality, China, 100032
      • Recruiting
      • CHN13-0
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • CHN23-0
  • Guangdong
    • Dongguan, Guangdong, China, 523000
      • Recruiting
      • CHN17-0
  • Henan
    • Henan, Henan, China, 450008
      • Recruiting
      • CHN06-0
    • Xinxiang, Henan, China, 453100
      • Recruiting
      • CHN12-0
  • Hubei
    • Hubei, Hubei, China, 430014
      • Recruiting
      • CHN04-0
    • Wuhan, Hubei, China, 00000
      • Recruiting
      • CHN26-0
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • CHN34-0
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • CHN11-0
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • CHN16-0
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • CHN35-0
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • CHN25-0
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Recruiting
      • CHN04-0
    • Shanghai, Shanghai Municipality, China, 200120
      • Recruiting
      • CHN01-0
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • CHN24-0
• Taiwan
  • Taipei
    • Taipei, Taipei, Taiwan
      • Recruiting
      • TWN01-0
    • Taipei, Taipei, Taiwan, 23561
      • Recruiting
      • TWN02-0
• United States
  • California
    • Los Angeles, California, United States, 90025
      • Recruiting
      • USA06-0
    • Los Angeles, California, United States, 90025
      • Recruiting
      • USA16-0
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Recruiting
      • USA01-0
  • Florida
    • Florida City, Florida, United States, 99208
      • Recruiting
      • USA08-0
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • USA10-0
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • USA11-0
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Recruiting
      • USA14-0
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • USA04-0
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • USA15-0
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • USA03-0
  • Texas
    • Anderson, Texas, United States, 46011
      • Recruiting
      • USA13-0
    • Houston, Texas, United States, 77030
      • Recruiting
      • USA12-0
  • Virginia
    • Virginia Beach, Virginia, United States, 22031
      • Recruiting
      • USA05-0
  • Washington
    • Puyallup, Washington, United States, 98373
      • Recruiting
      • USA09-0
    • Spokane, Washington, United States, 99208
      • Recruiting
      • USA07-0

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Cohort 2, DB-1311/BNT324+ DB-1305 /BNT325 combination therapy; Escalating combination dose levels of DB-1311/BNT324 and DB-1305/BNT325 to define RP2D and RP2D-1 in target population.	Drug: DB-1311/BNT324; Administered I.V.; Drug: DB-1305/BNT325; Administered I.V.
Experimental: Part 2 Arm 1: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic HCC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part2 Arm 3:RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic melanoma	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 5: RP2D of DB-1311/BNT324 +DB-1305/BNT325 and RP2D-1 of DB-1311/BNT324 +DB-1305/BNT325; In participants with advanced/unresectable metastatic NSCLC	Drug: DB-1311/BNT324; Administered I.V.; Drug: DB-1305/BNT325; Administered I.V.
Experimental: Part 1 Cohort 1A, DB-1311/BNT324+ BNT327 combination therapy; Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D (Recommended Phase 2 Dose) and RP2D-1 in target population.	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 2: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/ metastatic CC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 1 Cohort 1B, DB-1311/BNT324+ BNT327 combination therapy; Escalating combination dose levels of DB-1311/BNT324 and BNT327 to define RP2D and RP2D-1 in target population.	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 4: RP2D of DB-1311/BNT324 + BNT327; In participants with recurrent/metastatic HNSCC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 6: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic PSOC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 7: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic PDAC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 8: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic breast cancer	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 9: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic CRC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.
Experimental: Part 2 Arm 10: RP2D of DB-1311/BNT324 + BNT327; In participants with unresectable advanced/metastatic mCRPC	Drug: BNT327; Administered I.V.; Drug: DB-1311/BNT324; Administered I.V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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: Treatment-emergent adverse events (TEAEs) and treatment-emergent serious AE (TESAEs)	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]	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.	From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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: 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 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
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).	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).	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.	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)	From the time of initiation of the first dose of IMP to end of study, i.e., up to 72 months

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Collaborators: BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: April 9, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Melanoma; B7-H3; PD-L1/VEGF-A; TROP2 (Trophoblast cell surface antigen 2); ADC (antibody-drug conjugate); HNSCC (head and neck squamous cell carcinoma); HCC (hepatocellular carcinoma); NSCLC(non-small cell lung cancer); OC (ovarian cancer)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Carcinoma, Squamous Cell; Skin and Connective Tissue Diseases; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Hepatocellular; Ovarian Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma
• Other Study ID Numbers: DB-1311-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No