A Phase 1 Study of D3S-003 as Monotherapy in Participants With Advanced Solid Tumors With a KRAS p.G12D Mutation.

A Phase 1, Open-label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-003 Monotherapy in Participants With Advanced Solid Tumors With a KRAS p.G12D Mutation

This is a first-in-human (FIH) multicenter, open-label, dose-escalation Phase 1 clinical trial to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of D3S-003 in participants with advanced KRAS p.G12D mutant solid tumors.

Study Overview

• Status: Recruiting
• Conditions: KRAS P.G12D
• Intervention / Treatment: Drug: D3S-003

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • D3 Bio Investigative Site 1103
• South Korea
  • Seoul, South Korea, 03080
    • Recruiting
    • D3 Bio Investigative Site 1201
  • Seoul, South Korea, 03722
    • Recruiting
    • D3 Bio Investigative Site 1203
  • Seoul, South Korea, 06591
    • Recruiting
    • D3 Bio Investigative Site 1202
• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • D3 Bio Investigative Site 1402

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subjects must have histologically confirmed locally advanced, recurrent, or metastatic malignancy that has progressed following at least one line of standard therapy or where standard therapy has proven to be ineffective or intolerable or is considered inappropriate or when participation in a clinical trial of an investigational agent is considered a standard therapeutic option.
• Subjects must have documented presence of KRAS p.G12D mutation by a local test identified through tumor tissue or blood collected within the last 5 years.
• Subjects must have measurable disease per RECIST v1.1.
• Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject must have adequate organ and marrow function within the screening period.

Exclusion Criteria:

• Participant has any prior treatment with a specific KRAS G12D inhibitor/degrader or pan RAS inhibitor/degrader.
• Subject has uncontrolled intercurrent illness, including but not limited to serious chronic gastrointestinal conditions associated with diarrhea, ongoing or active infections, uncontrolled or significant cardiovascular disease, autoimmune or inflammatory disorders or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events (AEs), or compromise the ability of the subject to give written consent.
• Uncontrolled or untreated brain metastases
• Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy

NOTE: Other protocol inclusion/exclusion criteria may apply.

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: D3S-003; Part 1a Dose Escalation in subjects with KRAS p.G12D-mutated solid tumors (Once Daily Dosing) Part 1b Dose Escalation in subjects with KRAS p.G12D-mutated solid tumors (Twice Daily Dosing)	Drug: D3S-003; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Dose-Limiting Toxicities (DLTs)	From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.
Number of Participants with Adverse Events (AEs)	From screening visit until 30 days after the last dose (or specified in the protocol)
Maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs)	First dose up to 7 months
Phase 2 dose (RP2D)	First dose up to 7 months

Secondary Outcome Measures

Outcome Measure	Time Frame
D3S-003 concentration of drug immediately before the administration of next dose (Ctrough)	First dose up to 7 months
D3S-003 maximum observed plasma concentration (Cmax)	First dose up to 7 months
D3S-003 time to maximum plasma concentration (tmax)	First dose up to 7 months
D3S-003 half-life (t1/2)	First dose up to 7 months
D3S-003 area under the concentration-time curve (AUC)	First dose up to 7 months
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 7 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 7 months)
Disease Control Rate (DCR) 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 7 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 7 months)

Collaborators and Investigators

• Sponsor: D3 Bio (Wuxi) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2026
• Primary Completion (Estimated): January 11, 2028
• Study Completion (Estimated): January 11, 2028

Study Registration Dates

• First Submitted: March 3, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: KRAS P.G12D Mutation, Advanced solid tumors
• Other Study ID Numbers: D3S-003-100

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