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

Advanced Solid Tumor Clinical Trial

Official title:

A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1305 in Subjects With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05438329
• Other study ID #: DB-1305-O-1001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 19, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: July 2023
• Source: DualityBio Inc.
• Contact: Britney Winterberger
• Phone: +1-513-403-8568
• Email: britney.winterberger[@]tigermedgrp.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a multicenter, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 607
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• DB-1305/BNT325
Administered Injection of Vein (I.V.)

Combination Product:
• Pembrolizumab
Administered I.V.

Locations

Country	Name	City	State
China	Site 211	Bengbu	Anhui
China	Site 201	Changchun	Jilin
China	Site 206	Chengdu	Sichuan
China	Site 213	Fuzhou	Fujian
China	Site 208	Ganzhou	Jiangxi
China	Site 219	Guangzhou
China	Site 221	Guigang	Guanxi
China	Site 217	Hefei	Anhui
China	Site 216	Jinan	Shandong
China	Site 212	Linyi	Shandong
China	Site 209	Nanning	Guangxi
China	Site 207	Shanghai	Shanghai
China	Site 210	Shenyang	Liaoning
China	Site 220	Taizhou	Zhejiang
China	Site 203	Tianjin	Tianjin
China	Site 205	Wuhan	Hubei
China	Site 202	Zhengzhou	Henan
Puerto Rico	BRCR GLOBAL Puerto Rico LLC.	Mayaguez
United States	Site 110	Arlington	Texas
United States	Site 101	Canton	Ohio
United States	Site 103	Cerritos	California
United States	Site 106	Detroit	Michigan
United States	Site 107	Fairfax	Virginia
United States	Site 104	Houston	Texas
United States	Site 108	Los Angeles	California
United States	D&H Cancer Research Center Llc	Margate	Florida
United States	Site 105	Nashville	Tennessee
United States	Site 102	New York	New York
United States	Site 109	Plantation	Florida
United States	BRCR Medical Center Inc.	Tamarac	Florida

Sponsors (2)

Lead Sponsor	Collaborator
DualityBio Inc.	BioNTech SE

Countries where clinical trial is conducted

United States,  China,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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.
Primary	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.
Primary	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)
Primary	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.
Primary	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	Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Primary	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	Up to 30 days after last study treatment administration or before starting new anticancer treatment, whichever comes first.
Primary	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	Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1	Phase 1: ORR will be determined from tumor assessments by investigator per RECIST 1.1	with 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: duration of response (DoR) will be determined from tumor assessments by investigator per RECIST 1.1	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)
Secondary	Phase 1 & Phase 2a: disease-control rate (DCR)	Phase 1 & Phase 2a: disease-control rate (DCR)	with 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: time to response (TTR)	Phase 1 & Phase 2a: time to response (TTR)	with 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: progression free survival (PFS) will be determined from tumor assessments by investigator per RECIST 1.1	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)
Secondary	Phase 1 & Phase 2a: overall survival (OS)	Phase 1 & Phase 2a: overall survival (OS)	with 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic parameters: (the area under the concentration-time curve from the time zero to the last quantifiable concentration [AUC0-last] of DB-1305/BNT325	Phase 1 & Phase 2a: Pharmacokinetic parameters: (the area under the concentration-time curve from the time zero to the last quantifiable concentration [AUC0-last] of DB-1305/BNT325	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau [AUC0-tau] of DB-1305/BNT325	Phase 1 & Phase 2a: Pharmacokinetic parameters: the area under the concentration-time curve from time 0 to tau [AUC0-tau] of DB-1305/BNT325	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: peak observed concentration [Cmax] of DB-1305/BNT325	Phase 1 & Phase 2a: peak observed concentration [Cmax] of DB-1305/BNT325	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax [Tmax] of DB-1305/BNT325	Phase 1 & Phase 2a: Pharmacokinetic parameters: time to Cmax [Tmax] of DB-1305/BNT325	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration [Ctrough] of DB-1305/BNT325	Phase 1 & Phase 2a: Pharmacokinetic parameters: trough concentration [Ctrough] of DB-1305/BNT325	within 8 cycles (each cycle is 21 days)
Secondary	Phase 1 & Phase 2a: anti-drug antibody (ADA) prevalence: the proportion of subjects who are ADA positive at any point in time (at baseline and post-baseline). ADA incidence: the proportion of subjects having treatment-emergent ADA.	Phase 1 & Phase 2a: anti-drug antibody (ADA) prevalence: the proportion of subjects who are ADA positive at any point in time (at baseline and post-baseline). ADA incidence: the proportion of subjects having treatment-emergent ADA.	within 8 cycles (each cycle is 21 days)