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Recruiting NCT05150691

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

Phase I / Phase II Interventional HER2-positive Advanced Solid Tumor

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: DB-1303/BNT323, Pertuzumab Injection, Ritonavir, Itraconazole.
Who it may be relevant to
Registry conditions: HER2-positive Advanced Solid Tumor. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Australia, China, Puerto Rico, South Korea +1
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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-1303/BNT323 in Patients With 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-1303/BNT323 in subjects with advanced solid tumors that express HER2.

Detailed description

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.

Interventions

  • Biological DB-1303/BNT323
    Administered IV
  • Drug Pertuzumab Injection
    Administered IV
  • Drug Ritonavir
    Administered oral
  • Drug Itraconazole
    Administered oral

Primary outcome measures

  • Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. [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 [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. [Time frame: Up to follow-up period, approximately 1 year post-treatment]
  • Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 [Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment]
  • Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 [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 [Time frame: Up to follow-up period, approximately 1 year post-treatment]
  • Phase 2: 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]
  • Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. [Time frame: Up to follow-up period, approximately 1 year post-treatment]
  • Phase 2 (Dose Expansion 10 only): To evaluate the effect of ritonavir on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors [Time frame: up to safety follow-up visit, approx. 35 days post-treatment]
  • Phase 2 (Dose Expansion 10 only): To evaluate the effect of itraconazole on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors. [Time frame: up to safety follow-up visit, approx. 35 days post-treatment]
Secondary outcome measures (12)
  • Phase 1 & Phase 2: Pharmacokinetic-AUC [Time frame: Up to safety follow up visit, approx. 35 days post-treatment]
  • Phase 1 & Phase 2: Pharmacokinetic-Cmax [Time frame: Up to safety follow up visit, approx. 35 days post-treatment]
  • Phase 1 & Phase 2: Pharmacokinetic-Tmax [Time frame: Up to safety follow up visit, approx. 35 days post-treatment]
  • Phase 1 & Phase 2: Pharmacokinetic-T1/2 [Time frame: Up to safety follow up visit, approx. 35 days post-treatment]
  • Phase 1 & Phase 2: Pharmacokinetic-Ctrough [Time frame: Up to safety follow up visit, approx. 35 days post-treatment]
  • Phase 1 & Phase 2: Pharmacodynamics-ADA [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 [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 [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 [Time frame: Up to follow-up period, approximately 1 year post-treatment]
  • Phase 2: Time on Therapy [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 [Time frame: Up to follow-up period, approximately 1 year post-treatment]
  • Phase 1 and 2 Cohort b only: Progression-Free Survival [Time frame: Up to follow-up period, approximately 1 year post-treatment]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

China · 50 centers
  • The first affiliated hospital of Bengbu medical college — Bengbu
  • Anhui provincial hospital — Hefei
  • The Second Hospital of Anhui Medical University — Hefei
  • Beijing Cancer Hospital — Beijing
  • Cancer Hospital Chinese Academy of Medical Science — Beijing
  • The First Hospital of Jilin University — Hongcun
  • Chongqing University Cancer Hospital — Chongqing
  • The First affiliated Hospital of Chongqing Medical University — Chongqing
  • … and 42 more centers
United States · 35 centers
  • Helios Clinical Research — Cerritos
  • California Research Institute — Los Angeles
  • Sharp Memorial Hospital — San Diego
  • Washington Cancer Institute at MedStar Washington Hospital Center — Washington D.C.
  • Advanced Research LLC — Coral Springs
  • The Oncology Institute of Hope and Innovation — Lakeland
  • D&H Cancer Research Center LLC — Margate
  • HCA Mercy Hospital — Miami
  • … and 27 more centers
Taiwan · 7 centers

Center list to be confirmed — check the primary protocol.

South Korea · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers
  • Scientia Clinical Research LTD — Randwick
  • Macquarie Clinical Trials Unit — Sydney
  • Integrated Clinical Oncology Network Pty Ltd (Icon) — South Brisbane
  • Monash Health — Melbourne
Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05150691 · DB-1303-O-1001

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗