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NCT Number: NCT07456046

A Phase 1 Study of D3S-003 as 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.

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Key information

Conditions

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

D3 Bio Investigative Site 1103, Randwick, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

D3S-003

Drug

Oral Tablet

Primary outcomes

  1. Number of Participants with Dose-Limiting Toxicities (DLTs)

    Time frame: From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.

  2. Number of Participants with Adverse Events (AEs)

    Time frame: From screening visit until 30 days after the last dose (or specified in the protocol)

  3. Maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs)

    Time frame: First dose up to 7 months

  4. Phase 2 dose (RP2D)

    Time frame: First dose up to 7 months

Secondary outcomes

  1. D3S-003 concentration of drug immediately before the administration of next dose (Ctrough)

    Time frame: First dose up to 7 months

  2. D3S-003 maximum observed plasma concentration (Cmax)

    Time frame: First dose up to 7 months

  3. D3S-003 time to maximum plasma concentration (tmax)

    Time frame: First dose up to 7 months

  4. D3S-003 half-life (t1/2)

    Time frame: First dose up to 7 months

  5. D3S-003 area under the concentration-time curve (AUC)

    Time frame: First dose up to 7 months

  6. Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

    Time frame: Until disease progression or end of treatment (up to approximately 7 months)

  7. Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

    Time frame: Until disease progression or end of treatment (up to approximately 7 months)

  8. Disease Control Rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

    Time frame: Until disease progression or end of treatment (up to approximately 7 months)

  9. Progression-free survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

    Time frame: Until disease progression or end of treatment (up to approximately 7 months)

Study contacts

Contact information is provided by the study sponsor or research team.

Medical Director

CONTACT

[email protected]

+86 21 61635900

Sponsors and collaborators

Lead sponsor

D3 Bio (Wuxi) Co., Ltd

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Mar 6, 2026
Registry last updated
Jun 4, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.