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RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation

NCT ID: NCT05410145Sponsor: D3 Bio (Wuxi) Co., LtdLast updated: 2026-03-12

Summary

This is a first-in-human (FIH), multicenter, open-label, dose-escalation, and dose-expansion Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of D3S-001 or combination therapy in subjects with advanced KRAS p.G12C mutant solid tumors. D3S-001 will be taken daily by oral administration in 21-day treatment cycles.

Arms & interventions

  • DrugD3S-001

    Oral

  • DrugPembrolizumab

    Intravenous

  • DrugCisplatin

    Intravenous

  • DrugCarboplatin

    Intravenous

  • DrugPemetrexed

    Intravenous

  • DrugCetuximab

    Intravenous

Outcome measures

Primary

  • Number of Participants With Adverse Events (AEs)

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

  • Number of Participants With Dose-Limiting Toxicities (DLTs)

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

Secondary

  • D3S-001 maximum observed plasma concentration (Cmax)

    Time frame: Up to 24 months.

  • D3S-001 time to maximum plasma concentration (tmax)

    Time frame: Up to 24 months.

  • D3S-001 half-life (t1/2)

    Time frame: Up to 24 months.

  • D3S-001 area under the concentration-time curve (AUC)

    Time frame: Up to 24 months.

  • 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: Up to 24 months.

  • 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: Up to 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)

    Time frame: Up to 24 months.

  • 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: Up to 24 months.

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion: * Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing. * Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood. * Subject 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: * Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol. * Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations 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). * Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy. * Concurrent participation in any clinical research study involving treatment with any investigational drug, radiotherapy, or surgery, except for the nontreatment phases of these studies (e.g., follow-up phase). Other protocol inclusion/exclusion criteria may apply

Study locations (7)

D3 Bio Investigative Site 0402

Orange, California, 92868

Recruiting

D3 Bio Investigative Site 0407

Palo Alto, California, 94304-2205

Recruiting

D3 Bio Investigative Site 0404

Denver, Colorado, 80218-1238

Recruiting

D3 Bio Investigative Site 0406

Sarasota, Florida, 34232-6410

Recruiting

D3 Bio Investigative Site 0401

Detroit, Michigan, 48202-2608

Recruiting

D3 Bio Investigative Site 0405

Nashville, Tennessee, 37203

Recruiting

D3 Bio Investigative Site 0403

Houston, Texas, 77030

Recruiting

References

  • Cho BC, Lu S, Lee MA, Song Z, Park JJ, Lim SM, Li Z, Zhao J, Richardson G, Zhang Y, Zhang J, Liu A, Loong HH, Chen C, Wang J, Shen Y, Fan Z, Chen Q, Wang H, Zhang J, Chen ZJ, Johnson ML, Mok T. D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial. Nat Med. 2025 Aug;31(8):2768-2777. doi: 10.1038/s41591-025-03688-6. Epub 2025 Apr 29.(PubMed)