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

Phase 2Active Not RecruitingNCT05438329

DualityBio Inc.1,123 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

1,123

Conditions

Advanced Solid Tumor

Interventions

DB-1305/BNT325DRUG

Administered Injection of Vein (I.V.)

PembrolizumabCOMBINATION_PRODUCT

Administered I.V.

BNT327DRUG

Administered I.V.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (93)

Outcomes

Primary Outcomes

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

Time frame: up to 28 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

Time frame: 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

Time frame: 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

Time frame: At the end of Cycle 1 (each cycle is up to 21 days)

Phase 1: RP2D of DB-1305/BNT325

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

Time frame: 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)

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

Data from ClinicalTrials.gov

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Site 139

Bullhead City, Arizona, United States

Site 103

Cerritos, California, United States

Site 136

La Jolla, California, United States

Site 127

Los Angeles, California, United States

Site 133

Los Angeles, California, United States

Site 108

Los Angeles, California, United States

Site 131

Washington D.C., District of Columbia, United States

Site 122

Coral Springs, Florida, United States

Site 142

Hialeah, Florida, United States

Site 114

Margate, Florida, United States

...and 83 more locations