A Study of D3L-001 as Monotherapy in Subjects With HER2-Positive Advanced Solid Tumors

A Phase 1, Open-label Dose Escalation and Dose-Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3L-001 Monotherapy in Subjects With HER2-Positive Advanced Solid Tumors.

This first-in-human (FIH) study, multi-center, open-label, dose escalation and dose expansion Phase I study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary anti-tumor activity of D3L-001 in subjects with HER2-positive advanced solid tumors.

Study Overview

• Status: Recruiting
• Conditions: HER-2 Positive Advanced Solid Tumors
• Intervention / Treatment: Biological: D3L-001

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +86 21 61635900; Email: D3bio_CT@d3bio.com

Study Locations

• China
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150088
      • Recruiting
      • D3 Bio Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • D3 Bio Investigative Site
• United States
  • California
    • Stanford, California, United States, 94305
      • Recruiting
      • D3 Bio Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • D3 Bio Investigative Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • D3 Bio Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must have documented HER2 positivity (determined by immunohistochemistry [IHC], in situ hybridization [ISH], Next Generation Sequencing [NGS] or other analysis techniques as appropriate).
• Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject must have left ventricular ejection fraction (LVEF) ≥50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within the screening period.
• Subject must have adequate organ and marrow function within the screening period.

Exclusion Criteria:

• Subject has any prior treatment with anti-CD47 or SIRPα agent.
• Subject has major surgery or radiotherapy, immunostimulatory agents, investigational agents, or any other anticancer treatment including chemotherapy, targeted therapy, biologics that is not completed 28 days before first dose of study medication.
• Subject has immunosuppressive medication that is not completed 14 days before the first dose of study medication.
• Subject has uncontrolled intercurrent illness that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
• Subject has unresolved treatment-related toxicities from previous anticancer therapy of NCI CTCAE Grade ≥2 (with exception of vitiligo or alopecia).
• Judgment by the Investigator that the subject should not participate in the study if the subject is unlikely to comply with study procedures, restrictions, and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: D3L-001; Part 1 Dose Escalation in subjects with HER2-positive advanced solid tumors; Cohort 1 (starting dose); Cohort 2; Cohort 3; Cohort 4; Cohort 5 Part 2 Dose Expansion; Cohort A for subjects with HER2-positive advanced breast cancer; Cohort B for subjects with HER2-positive advanced gastric cancer/gastroesophageal junction cancer	Biological: D3L-001; Intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs)	Screening until Safety Follow Up visit (30 days after the last dose)
Maximum Tolerated Dose based on Dose-Limiting Toxicities (DLTs)	At the end of Cycle 1 (each cycle is 21 days).

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Until disease progression or end of treatment (up to approximately 24 months)
Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Until disease progression or end of treatment (up to approximately 24 months)
D3L-001 minimum serum concentration (Ctrough)	First dose up to 6 months
D3L-001 maximum observed plasma concentration (Cmax)	First dose up to 6 months
D3L-001 time to maximum plasma concentration (tmax)	First dose up to 6 months
D3L-001 half-life (t1/2)	First dose up to 6 months
D3L-001 area under the concentration-time curve (AUC)	First dose up to 6 months
Incidence of anti-drug antibodies (ADA) to D3L-001	First dose up to 6 months
Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)	Until disease progression or end of treatment (up to approximately 24 months)
Disease control rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1	Until disease progression or end of treatment (up to approximately 24 months)
Pre- and post-dose levels of CD47 receptor occupancy in particular cell types from peripheral blood	First dose up to 6 months

Collaborators and Investigators

• Sponsor: D3 Bio (Wuxi) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2023
• Primary Completion (Estimated): March 11, 2026
• Study Completion (Estimated): March 11, 2026

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Actual): July 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; HER-2 Positive
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: D3L-001-100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No