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

Overview

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

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

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Primary Purpose: Treatment
  • Masking: None (Open Label)
• Study Primary Completion Date: June 30, 2025

Detailed Description

This is a multicenter, non-randomized, 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.

Interventions

• Drug: DB-1305
  • Administered I.V.

Arms, Groups and Cohorts

• Experimental: DB-1305 Dose Level 1
  • Enrolled Subjects will receive a single-dose of DB-1305 at Dose Level 1 on Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Level 2
  • Enrolled Subjects will receive a single-dose of DB-1305 at Dose Level 2 on Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Level 3
  • Enrolled Subjects will receive a single-dose of DB-1305 at Dose Level 3 on Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Level 4
  • Enrolled Subjects will receive a single-dose of DB-1305 at Dose Level 4 on Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Level 5
  • Enrolled Subjects will receive a single-dose of DB-1305 at Dose Level 5 on Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Expansion 1
  • Enrolled Subjects with advanced/unresectable, recurrent, or metastatic SCLC who have progressed on or after standard systemic treatments will receive a single-dose of DB-1305 on a selected dose level (RP2D) Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Expansion 2
  • Enrolled Subjects with advanced/unresectable, recurrent, or metastatic HR positive and HER2 negative breast cancer (BC) who have progressed on or after standard systemic treatments will receive a single-dose of DB-1305 on a selected dose level (RP2D) Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Expansion 3
  • Enrolled Subjects with advanced/unresectable, recurrent, or metastatic Non-Small Cell Lung Cancer (NSCLC) without harboring an EGFR-sensitizing mutation or ALK gene translocation or other onco-driver gene mutations which have available targeted therapies and have progressed on or after standard systemic treatments will receive a single-dose of DB-1305 on a selected dose level (RP2D) Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Expansion 4
  • Enrolled Subjects with advanced/unresectable, recurrent, or metastatic Triple Negative Breast Cancer (TNBC) who have progressed on or after standard systemic treatments and without prior treatment of sacituzumab govitecan will receive a single-dose of DB-1305 on a selected dose level (RP2D) Day 1 of each cycle Q3W
• Experimental: DB-1305 Dose Expansion 5
  • Enrolled Subjects with advanced/unresectable, recurrent, or metastatic Triple Negative Breast Cancer (TNBC) with treatment failure on sacituzumab govitecan will receive a single-dose of DB-1305 on a selected dose level (RP2D) Day 1 of each cycle Q3W

Clinical Trial Outcome Measures

Primary Measures

• Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
  • Time Frame: up to 21 days after Cycle 1 Day 1
  • Percentage of participants in Part 1 with DLTs
• Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.
  • Time Frame: Up to follow-up period, approximately 1 year post-treatment
  • Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
• Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
  • Time Frame: Up to follow-up period, approximately 1 year post-treatment
  • Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0
• Maximum Tolerated Dose (MTD) of DB-1305
  • Time Frame: 12 months
  • MTD on the data collected during Part 1
• Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1305
  • Time Frame: 12 months
  • RP2D of DB-1305 based on the data collected during Part 1
• Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
  • Time Frame: Up to follow-up period, approximately 1 year post-treatment
  • Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
• Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
  • Time Frame: Up to follow-up period, approximately 1 year post-treatment
  • Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0
• Phase 2a: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
  • Time Frame: Up to follow-up period, approximately 1 year post-treatment
  • The percentage of subjects who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks

Secondary Measures

• Phase 1 & Phase 2a: Pharmacokinetic-AUC
  • Time Frame: within 8 cycles (each cycle is 21 days)
  • Area under the concentration-time curve from time 0 to infinity of DB-1305
• Phase 1 & Phase 2a: Pharmacokinetic-Cmax
  • Time Frame: within 8 cycles (each cycle is 21 days)
  • Maximum observed plasma concentration (Cmax) of DB-1305
• Phase 1 & Phase 2a: Pharmacokinetic-Tmax
  • Time Frame: within 8 cycles (each cycle is 21 days)
  • Time to Cmax of DB-1305
• Phase 1 & Phase 2a: Pharmacokinetic-T1/2
  • Time Frame: within 8 cycles (each cycle is 21 days)
  • Terminal elimination half-life

Participating in This Clinical Trial

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 response evaluation criteria in solid tumors (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 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 no contraindication. – 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 interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening. – 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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • DualityBio Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Raymond Zhao, MD, Study Director, DualityBio Inc.
• Overall Contact(s)
  • Britney Winterberger, +1-513-403-8568, britney.winterberger@tigermedgrp.com