Clinical trial NCT05957536: A Study of D3L-001 as Monotherapy in Subjects With HER2-Positive Advanced Solid Tumors
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HER-2 Positive Advanced Solid Tumors
Keywords: HER-2 Positive
Advanced Solid Tumors
Lead sponsor: D3 Bio (Wuxi) Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-07-24
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Screening until Safety Follow Up visit (30 days after the last dose)
measure: Maximum Tolerated Dose based on Dose-Limiting Toxicities (DLTs)
timeFrame: At the end of Cycle 1 (each cycle is 21 days).
Secondary outcomes:
measure: D3L-001 minimum serum concentration (Ctrough)
timeFrame: First dose up to 6 months
measure: D3L-001 maximum observed plasma concentration (Cmax)
timeFrame: First dose up to 6 months
measure: D3L-001 time to maximum plasma concentration (tmax)
timeFrame: First dose up to 6 months
measure: D3L-001 half-life (t1/2)
timeFrame: First dose up to 6 months
measure: D3L-001 area under the concentration-time curve (AUC)
timeFrame: First dose up to 6 months
measure: Incidence of anti-drug antibodies (ADA) to D3L-001
timeFrame: First dose up to 6 months
measure: Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Disease control rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: Until disease progression or end of treatment (up to approximately 24 months)
measure: Pre- and post-dose levels of CD47 receptor occupancy in particular cell types from peripheral blood
timeFrame: First dose up to 6 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: D3 Bio Investigative Site
state: California
city: Boston
country: United States
facility: D3 Bio Investigative Site
state: Massachusetts
city: New York
country: United States
facility: D3 Bio Investigative Site
state: New York
city: San Antonio
country: United States
facility: D3 Bio Investigative Site
state: Texas
city: Sydney
country: Australia
facility: D3 Bio Investigative Site
state: New South Wales
city: Malvern
country: Australia
facility: D3 Bio Investigative Site
state: Victoria
city: Harbin
country: China
facility: D3 Bio Investigative Site
state: Heilongjiang
city: Shanghai
country: China
facility: D3 Bio Investigative Site
state: Shanghai
city: Hangzhou
country: China
facility: D3 Bio Investigative Site
state: Zhejiang
Study officials:
References: