A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors

Phase 2RecruitingNCT05150691

DualityBio Inc.796 enrolled

Overview

This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors that express HER2.

This is a multicenter, non-randomized (Except for Dose Expansion 1 and Dose Expansion 9 cohorts), open-label, multiple-dose, 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 MTD/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 HER2-expressing malignant solid tumors.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

796

Conditions

HER2-positive Advanced Solid Tumor

Interventions

DB-1303/BNT323BIOLOGICAL

Administered IV

Pertuzumab InjectionDRUG

Administered IV

RitonavirDRUG

Administered oral

Itraconazole

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available. * At least 1 measurable lesion (per RECIST 1.1) * Provide signed informed consent * ECOG performance status (PS) of 0-1. * LVEF ≥ 50% by ECHO or MUGA * Adequate organ functions * Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing. * Life expectancy of ≥ 3 months. Additional Inclusion Criteria for Part 2 Expansion Group 9: 1\. Has pathologically documented advanced/unresectable, recurrent, or metastatic EC (including UCS and USPC) and has progressed on or after at least 1 line of systemic treatment including platinum-based therapy and exposure to ICI but no more than prior 3 lines of therapy for advanced/unresectable, or metastatic disease. Note: endocrine therapy will not qualify as a systemic therapy line. Exclusion Criteria: * History of symptomatic CHF (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment. * History of myocardial infarction or unstable angina within 6 months before Day 1. * Average QTcF \> 450 ms in males and \> 470 ms in females * History of clinically significant lung diseases * Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. * HIV infection with AIDS defining illness or active viral hepatitis. * Clinically active brain metastases * Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline. * A known hypersensitivity to either the drug substances or inactive ingredients in the drug product. * Part 2 (expansion) Only:Multiple primary malignancies within 3 years, except adequately resected non- melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.

Locations (102)

Outcomes

Primary Outcomes

Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.

Percentage of participants in Part 1 with DLTs

Time frame: up to 21 days after C1D1

Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0

Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment

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 to follow-up period, approximately 1 year post-treatment

Phase 1: Maximum Tolerated Dose (MTD) of DB-1303

MTD on the data collected during Part 1

Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment

Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303

RP2D of DB-1303 based on the data collected during Part 1

Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment

Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0

Phase 2: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

Central Contacts

Britney Winterberger

CONTACT

+1-513-403-8568 britney.winterberger@tigermedgrp.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Helios Clinical Research

Cerritos, California, United States

ACTIVE_NOT_RECRUITING

California Research Institute

Los Angeles, California, United States

ACTIVE_NOT_RECRUITING

Sharp Memorial Hospital

San Diego, California, United States

ACTIVE_NOT_RECRUITING

Washington Cancer Institute at MedStar Washington Hospital Center

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

ACTIVE_NOT_RECRUITING

Advanced Research LLC

Coral Springs, Florida, United States

ACTIVE_NOT_RECRUITING

The Oncology Institute of Hope and Innovation

Lakeland, Florida, United States

ACTIVE_NOT_RECRUITING

D&H Cancer Research Center LLC

Margate, Florida, United States

ACTIVE_NOT_RECRUITING

HCA Mercy Hospital

Miami, Florida, United States

WITHDRAWN

BRCR Medical Center Inc.

Plantation, Florida, United States

ACTIVE_NOT_RECRUITING

BRCR Medical Center Inc.

Tamarac, Florida, United States

ACTIVE_NOT_RECRUITING

...and 92 more locations

Secondary Outcomes

Phase 1 & Phase 2: Pharmacokinetic-AUC

Area under the concentration-time curve from time 0 to infinity of DB-1303

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & Phase 2: Pharmacokinetic-Cmax

Maximum observed plasma concentration (Cmax) of DB-1303

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & Phase 2: Pharmacokinetic-Tmax

Time to Cmax of DB-1303

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & Phase 2: Pharmacokinetic-T1/2

Terminal elimination half-life

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & Phase 2: Pharmacokinetic-Ctrough

Trough concentration of DB-1303

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & Phase 2: Pharmacodynamics-ADA

Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline.

Time frame: Up to safety follow up visit, approx. 35 days post-treatment

Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1

Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1.

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1

The duration of time from date of first CR or PR to date of progressive disease or death due to any cause, whichever comes first using RECIST V1.1

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1

The duration of time when receiving the first dose of study drug to the first date that is evaluated as either CR or PR using RECIST V1.1

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 2: Time on Therapy

The duration of time from participant receiving first dose of study drug to the last dose + 21 days

Time frame: Up to 21 days after the participant's last dose

Phase 2: Percent change in target lesions as assessed by RECIST 1.1

The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 1 and 2 Cohort b only: Progression-Free Survival

Time from subject receiving the first dose to disease progression or death by any cause

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 1 and 2 Cohort b only: Overall Survival

Time from subject receiving the first dose to death by any cause

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1

The percentage of subjects who had a best response of CR or PR

Time frame: Up to follow-up period, approximately 1 year post-treatment

Phase 2 Cohort b Only: Percentage of ORR as assessed by IRC and as assessed by investigator based on RECIST 1.1 for HER2-expressing subjects and in subjects with prior ICI treatment

The percentage of subjects who had a best response of CR or PR, for Cohort 2b only

Time frame: Up to follow-up period, approximately 1 year post-treatment

To evaluate the safety of DB-1303 with/without ritonavir or itraconazole

Percentage of Participants with Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAE), TEAEs \>/= G3, or TEAEs leading to dose reduction, interruption or discontinuation, Adverse Events of Special Interest, (AESIs), abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).

Time frame: Up to follow-up period, approximately 1 year post-treatment