A Study of D3S-001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation

NCT05410145 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D3S-001-1002023-508517-16
• Study Type: interventional
• Target: 442
• Locations: 10 countries
• Sites: 52

Brief 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.

Conditions

KRAS P.G12C

Keywords

KRAS p.G12C; Mutation; advanced solid tumors

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Adverse Events (AEs)

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

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

  From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.

Secondary Outcomes (8)

• D3S-001 maximum observed plasma concentration (Cmax)

  Up to 24 months.

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

  Up to 24 months.

• D3S-001 half-life (t1/2)

  Up to 24 months.

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

  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)

  Up to 24 months.

Study Arms (4)

D3S-001 monotherapy

EXPERIMENTAL

Part 1: Dose Escalation, D3S-001 administered orally. Part 2 and Part 3a Arm C: Dose Expansion, D3S-001 administered orally in selected cancer type patients. Part 4a: Dose Optimization, D3S-001 administered orally in selected cancer type patients.

Drug: D3S-001

D3S-001 and pembrolizumab

EXPERIMENTAL

Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Pembrolizumab administered intravenously.

Drug: D3S-001; Drug: Pembrolizumab

D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)

EXPERIMENTAL

Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + pemetrexed administered intravenously

Drug: D3S-001; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed

D3S-001 and Cetuximab

EXPERIMENTAL

Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cetuximab administered intravenously.

Drug: D3S-001; Drug: Cetuximab

Interventions

Pemetrexed DRUG

Intravenous

D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)

D3S-001 DRUG

Oral

D3S-001 and Cetuximab; D3S-001 and pembrolizumab; D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed); D3S-001 monotherapy

Pembrolizumab DRUG

Intravenous

D3S-001 and pembrolizumab

Cisplatin DRUG

Intravenous

D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)

Carboplatin DRUG

Intravenous

D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)

Cetuximab DRUG

Intravenous

D3S-001 and Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• D3 Bio (Wuxi) Co., Ltd: lead

Study Sites (52)

D3 Bio Investigative Site 0402

Orange, California, 92868, United States

RECRUITING

D3 Bio Investigative Site 0407

Palo Alto, California, 94304-2205, United States

RECRUITING

D3 Bio Investigative Site 0404

Denver, Colorado, 80218-1238, United States

RECRUITING

D3 Bio Investigative Site 0406

Sarasota, Florida, 34232-6410, United States

RECRUITING

D3 Bio Investigative Site 0401

Detroit, Michigan, 48202-2608, United States

RECRUITING

D3 Bio Investigative Site 0405

Nashville, Tennessee, 37203, United States

RECRUITING

D3 Bio Investigative Site 0403

Houston, Texas, 77030, United States

RECRUITING

D3 Bio Investigative Site 0102

Sydney, New South Wales, 2109, Australia

RECRUITING

D3 Bio Investigative Site 0101

Malvern, Victoria, 3144, Australia

RECRUITING

D3 Bio Investigative Site 0105

Melbourne, Victoria, 3000, Australia

RECRUITING

D3 Bio Investigative Site 0103

Nedlands, Western Australia, 6009, Australia

RECRUITING

D3 Bio Investigative Site 0104

Bedford Park, 5042, Australia

RECRUITING

D3 Bio Investigative Site 0303

Beijing, Beijing Municipality, 100036, China

RECRUITING

D3 Bio Investigative Site 0306

Guangzhou, Guangdong, 510120, China

RECRUITING

D3 Bio Investigative Site 0305

Hangzhou, Hangzhou, 310022, China

RECRUITING

D3 Bio Investigative Site 0307

Harbin, Heilongjiang, 150081, China

RECRUITING

D3 Bio Investigative Site 0309

Wuhan, Hubei, 43000, China

RECRUITING

D3 Bio Investigative Site 0312

Wuhan, Hubei, 430079, China

RECRUITING

D3 Bio Investigative Site 0304

Nanchang, Jiangxi, 330008, China

RECRUITING

D3 Bio Investigative Site 0302

Shenyang, Liaoning, 110042, China

RECRUITING

D3 Bio Investigative Site 0310

Jinan, Shandong, 250117, China

RECRUITING

D3 Bio Investigative Site 0301

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

D3 Bio Investigative Site 0308

Shanghai, Shanghai Municipality, 201801, China

RECRUITING

D3 Bio Investigative Site 0316

Chengdu, Sichuan, 610041, China

RECRUITING

D3 Bio Investigative Site 0311

Hangzhou, Zhejiang, 310003, China

RECRUITING

D3 Bio Investigative Site 0315

Changsha, 410013, China

RECRUITING

D3 Bio Investigative Site 0314

Hefei, 230000, China

RECRUITING

D3 Bio Investigative Site 0313

Zhengzhou, 450003, China

RECRUITING

D3 Bio Investigative Site 0804

Bordeaux, 33000, France

RECRUITING

D3 Bio Investigative Site 0803

Lyon, 69373, France

RECRUITING

D3 Bio Investigative Site 0801

Rennes, 35033, France

RECRUITING

D3 Bio Investigative Site 0802

Villejuif, 94805, France

RECRUITING

D3 Bio Investigative Site 1003

Cologne, North Rhine-Westphalia, 45147, Germany

RECRUITING

D3 Bio Investigative Site 1002

Hamburg, 20249, Germany

RECRUITING

D3 Bio Investigative Site 0501

Shatin, 999077, Hong Kong

RECRUITING

D3 Bio Investigative Site 0905

Candiolo, 10060, Italy

RECRUITING

D3 Bio Investigative Site 0902

Milan, 20141, Italy

RECRUITING

D3 Bio Investigative Site 0904

Naples, 80131, Italy

RECRUITING

D3 Bio Investigative Site 0901

Rome, 00144, Italy

RECRUITING

D3 Bio Investigative Site 0903

Siena, 53100, Italy

RECRUITING

D3 Bio Investigative Site 0601

Kashiwa, 277-8577, Japan

RECRUITING

D3 Bio Investigative Site 0602

Tokyo, 104-0045, Japan

RECRUITING

D3 Bio Investigative Site 0204

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

D3 Bio Investigative Site 0202

Seoul, 06591, South Korea

RECRUITING

D3 Bio Investigative Site 0203

Seoul, 120-752, South Korea

RECRUITING

D3 Bio Investigative Site 0201

Seoul, 138-736, South Korea

WITHDRAWN

D3 Bio Investigative Site 0706

Barcelona, 08023, Spain

RECRUITING

D3 Bio Investigative Site 0701

Barcelona, 08035, Spain

RECRUITING

D3 Bio Investigative Site 0704

Madrid, 28046, Spain

RECRUITING

D3 Bio Investigative Site 0705

Madrid, 28050, Spain

RECRUITING

D3 Bio Investigative Site 0703

Valencia, 46010, Spain

RECRUITING

D3 Bio Investigative Site 0702

Valencia, 46026, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 40301557 DERIVED

MeSH Terms

Interventions

pembrolizumab; Cisplatin; Carboplatin; Pemetrexed; Cetuximab

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Officials

• Cheng Chen, MD

  D3 Bio (Wuxi) Co., Ltd

  STUDY DIRECTOR

Central Study Contacts

Medical Director

CONTACT

+86 21 61635900; D3bio_CT@d3bio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2022
• First Posted: June 8, 2022
• Study Start: August 3, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); US (7); CN (16); ES (6); DE (2); IT (5); JP (2); FR (4); HK (1); KR (4)