First-in-human Study of DB-1305/BNT325 for Advanced/Metastatic Solid Tumors

NCT05438329 | Recruiting Phase 1 FDA Drug

• 1 other identifier: DB-1305-O-1001
• Study Type: interventional
• Target: 1,123
• Locations: 3 countries
• Sites: 30

Brief Summary

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1305/BNT325 in subjects with advanced solid tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (8)

• Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

  Percentage of participants in Part 1 with DLTs

  up to 21 days after Cycle 1 Day 1

• Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.

  Percentage of participants with TEAEs in Part 1 graded according to NCI CTCAE v5.0

  Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.

• Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.

  Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0

  Up 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.

• Maximum Tolerated Dose (MTD) of DB-1305/BNT325

  MTD on the data collected during Part 1

  At the end of Cycle 1 (each cycle is 21 days)

• Phase 1: RP2D of DB-1305/BNT325

  RP2D of DB-1305/BNT325 based on the data collected during Part 1

  From first study treatment administration until the initiation of Phase 2a, approximately up to 12 months.

• Phase 2a: Percentage of Participants with TEAEs as assessed by CTCAE v5.0.

  Percentage of participants with TEAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3)

  Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.

• Phase 2a: Percentage participants with SAEs as assessed by CTCAE v5.0.

  Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0 (secondary outcome measure in cohort 3)

  Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.

• Phase 2a: Objective Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

  The percentage of subjects who had a best response rating of CR and PR

  Up to disease progression or death or before starting new anticancer treatment or withdrawal from the trial, whichever comes first, approximately up to 12 months.

Secondary Outcomes (12)

• Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1

  with 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator per RECIST 1.1

  with 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: disease-control rate (DCR)

  with 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: time to response (TTR)

  with 8 cycles (each cycle is 21 days)

• Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator per RECIST 1.1

  with 8 cycles (each cycle is 21 days)

Study Arms (30)

DB-1305/BNT325 Dose Level 1

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 1

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 2

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 2

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 3

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 3

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 4

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 4

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 5

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 5

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 6

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 6

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 7

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 7

Drug: DB-1305/BNT325

DB-1305/BNT325 in combination with pembrolizumab

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 in combination with pembrolizumab

Drug: DB-1305/BNT325; Combination Product: Pembrolizumab

DB-1305/BNT325 Dose Expansion 1

EXPERIMENTAL

subjects with Non-Small Cell Lung Cancer (NSCLC) with actionable genetic alterations (AGAs) who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 2

EXPERIMENTAL

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 3

EXPERIMENTAL

Enrolled subjects with OC who will receive DB-1305/BNT325 on either dose level 1 or dose level 2

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 4

EXPERIMENTAL

Enrolled subjects with BC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 5

EXPERIMENTAL

Enrolled subjects with Triple-Negative Breast Cancer (TNBC) who have progressed on or after standard systemic treatments and without prior treatment of sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 6

EXPERIMENTAL

Enrolled subjects with TNBC with treatment failure on sacituzumab govitecan who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 7

EXPERIMENTAL

Enrolled subjects with EC who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 8

EXPERIMENTAL

Enrolled subjects with malignant mesothelioma will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 9

EXPERIMENTAL

Enrolled subjects with Cervical Cancer (CC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 Dose Expansion 10

EXPERIMENTAL

Enrolled subjects with pancreatic cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion 11

EXPERIMENTAL

Enrolled subjects with Castration-Resistant Prostate Cancer (CRPC) who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion PB1

EXPERIMENTAL

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with pembrolizumab

Drug: DB-1305/BNT325; Combination Product: Pembrolizumab

Experimental: DB-1305/BNT325 Dose Level 8

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 8

Drug: DB-1305/BNT325

Experimental: DB-1305/BNT325 in combination with BNT327

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Experimental: DB-1305/BNT325 Dose Expansion PM1

EXPERIMENTAL

Enrolled subjects with NSCLC without AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Experimental: DB-1305/BNT325 Dose Expansion PM2

EXPERIMENTAL

Enrolled subjects with NSCLC with AGAs who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Experimental: DB-1305/BNT325 Dose Expansion PM3

EXPERIMENTAL

Enrolled subjects with CC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Experimental: DB-1305/BNT325 Dose Expansion PM4

EXPERIMENTAL

Enrolled subjects with OC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Experimental: DB-1305/BNT325 Dose Expansion PM5

EXPERIMENTAL

Enrolled subjects with TNBC who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

DB-1305/BNT325 Dose Expansion 12

EXPERIMENTAL

Enrolled subjects with head and neck cancer who will receive DB-1305/BNT325 on a selected dose level (RP2D)

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Level 9

EXPERIMENTAL

Enrolled subjects will receive DB-1305/BNT325 at Dose Level 9

Drug: DB-1305/BNT325

DB-1305/BNT325 Dose Expansion PM6

EXPERIMENTAL

Enrolled subjects with NSCLC without AGA who will receive DB-1305/BNT325 on a selected dose level in combination with BNT327

Drug: DB-1305/BNT325; Drug: BNT327

Interventions

DB-1305/BNT325 DRUG

Administered Injection of Vein (I.V.)

Also known as: DB-1305/BNT325 for Injection

DB-1305/BNT325 Dose Expansion 1; DB-1305/BNT325 Dose Expansion 11; DB-1305/BNT325 Dose Expansion 12; DB-1305/BNT325 Dose Expansion 2; DB-1305/BNT325 Dose Expansion 3; DB-1305/BNT325 Dose Expansion 4; DB-1305/BNT325 Dose Expansion 5; DB-1305/BNT325 Dose Expansion 6; DB-1305/BNT325 Dose Expansion 7; DB-1305/BNT325 Dose Expansion 8; DB-1305/BNT325 Dose Expansion 9; DB-1305/BNT325 Dose Expansion PB1; DB-1305/BNT325 Dose Expansion PM6; DB-1305/BNT325 Dose Level 1; DB-1305/BNT325 Dose Level 2; DB-1305/BNT325 Dose Level 3; DB-1305/BNT325 Dose Level 4; DB-1305/BNT325 Dose Level 5; DB-1305/BNT325 Dose Level 6; DB-1305/BNT325 Dose Level 7; DB-1305/BNT325 Dose Level 9; DB-1305/BNT325 in combination with pembrolizumab; Experimental: DB-1305/BNT325 Dose Expansion 10; Experimental: DB-1305/BNT325 Dose Expansion PM1; Experimental: DB-1305/BNT325 Dose Expansion PM2; Experimental: DB-1305/BNT325 Dose Expansion PM3; Experimental: DB-1305/BNT325 Dose Expansion PM4; Experimental: DB-1305/BNT325 Dose Expansion PM5; Experimental: DB-1305/BNT325 Dose Level 8; Experimental: DB-1305/BNT325 in combination with BNT327

Pembrolizumab COMBINATION_PRODUCT

Administered I.V.

DB-1305/BNT325 Dose Expansion PB1; DB-1305/BNT325 in combination with pembrolizumab

BNT327 DRUG

Administered I.V.

DB-1305/BNT325 Dose Expansion PM6; Experimental: DB-1305/BNT325 Dose Expansion PM1; Experimental: DB-1305/BNT325 Dose Expansion PM2; Experimental: DB-1305/BNT325 Dose Expansion PM3; Experimental: DB-1305/BNT325 Dose Expansion PM4; Experimental: DB-1305/BNT325 Dose Expansion PM5; Experimental: DB-1305/BNT325 in combination with BNT327

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults (defined as ≥ 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consent).
• Histologically or cytologically confirmed unresectable advanced/ metastatic solid tumors who have relapsed or progressed on or after standard systemic treatments or for which no standard treatment is available.
• At least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria.
• Has a life expectancy of ≥ 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.
• Has Left Ventricular Ejection Fraction (LVEF) ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
• Has adequate organ functions within 7 days prior to Day 1 of Cycle 1.
• Has adequate treatment washout period prior to Day 1 of Cycle 1.
• Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of Trop-2 level and other biomarkers if not contraindicated.
• Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.

You may not qualify if:

• Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
• Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
• Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate.
• Has a medical history of non-infectious Interstitial Lung Diseases (ILD)/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has a lung-specific intercurrent clinically significant illness.
• Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
• Subjects have human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS) defining illness are not eligible for enrollment; However, subjects have had HIV infection with a cluster of differentiation 4 (CD4)+ T cell count \> 350 cells/µL and no history of an AIDS-defining illness are eligible for entry.

Sponsors & Collaborators

• DualityBio Inc.: lead
• BioNTech SE: collaborator

Study Sites (30)

Site 103

Cerritos, California, 90703, United States

RECRUITING

Site 108

Los Angeles, California, 90095, United States

RECRUITING

D&H Cancer Research Center Llc

Margate, Florida, 33063, United States

RECRUITING

Site 109

Plantation, Florida, 33322, United States

RECRUITING

BRCR Medical Center Inc.

Tamarac, Florida, 33321, United States

RECRUITING

Site 106

Detroit, Michigan, 48201, United States

RECRUITING

Site 102

New York, New York, 10065, United States

RECRUITING

Site 101

Canton, Ohio, 44718, United States

RECRUITING

Site 105

Nashville, Tennessee, 37203, United States

RECRUITING

Site 110

Arlington, Texas, 76017, United States

RECRUITING

Site 104

Houston, Texas, 77030, United States

RECRUITING

Site 107

Fairfax, Virginia, 22031, United States

RECRUITING

Site 211

Bengbu, Anhui, 233099, China

RECRUITING

Site 217

Hefei, Anhui, 230031, China

RECRUITING

Site 213

Fuzhou, Fujian, 350001, China

NOT YET RECRUITING

Site 209

Nanning, Guangxi, 531200, China

RECRUITING

Site 221

Guigang, Guanxi, 537100, China

RECRUITING

Site 202

Zhengzhou, Henan, 450000, China

RECRUITING

Site 205

Wuhan, Hubei, 430021, China

NOT YET RECRUITING

Site 208

Ganzhou, Jiangxi, 341006, China

RECRUITING

Site 201

Changchun, Jilin, 130012, China

RECRUITING

Site 210

Shenyang, Liaoning, 110042, China

RECRUITING

Site 216

Jinan, Shandong, 250117, China

RECRUITING

Site 212

Linyi, Shandong, 276304, China

RECRUITING

Site 207

Shanghai, Shanghai Municipality, 201315, China

RECRUITING

Site 206

Chengdu, Sichuan, 611135, China

NOT YET RECRUITING

Site 203

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Site 220

Taizhou, Zhejiang, 317004, China

RECRUITING

Site 219

Guangzhou, China

RECRUITING

BRCR GLOBAL Puerto Rico LLC.

Mayagüez, 00682, Puerto Rico

RECRUITING

MeSH Terms

Interventions

Injections; pembrolizumab

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Lily Hu

  DualityBio Inc.

  STUDY DIRECTOR

Central Study Contacts

Tyler McCullars

CONTACT

(404) 954-1826; tyler.mccullars@tigermedgrp.com

Cathy Li

CONTACT

201-503-5410; cathy.li@dualitybiologics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: June 29, 2022
• Study Start: July 19, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

PR (1); CN (17); US (12)