Recruiting NCT05410145

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

Phase I / Phase II Interventional KRAS P.G12C

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: D3S-001, Pembrolizumab, Cisplatin, Carboplatin.
Who it may be relevant to: Registry conditions: KRAS P.G12C. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Australia, China, France, Germany +5
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

Drug D3S-001
Oral
Drug Pembrolizumab
Intravenous
Drug Cisplatin
Intravenous
Drug Carboplatin
Intravenous
Drug Pemetrexed
Intravenous
Drug Cetuximab
Intravenous

Primary outcome measures

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 outcome measures (8)

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Non-randomized
Model: Sequential
Masking: Open label
Primary purpose: Treatment

Study locations

China · 16 centers

D3 Bio Investigative Site 0303 — Beijing
D3 Bio Investigative Site 0306 — Guangzhou
D3 Bio Investigative Site 0305 — Hangzhou
D3 Bio Investigative Site 0307 — Harbin
D3 Bio Investigative Site 0309 — Wuhan
D3 Bio Investigative Site 0312 — Wuhan
D3 Bio Investigative Site 0304 — Nanchang
D3 Bio Investigative Site 0302 — Shenyang
… and 8 more centers

United States · 7 centers

D3 Bio Investigative Site 0402 — Orange
D3 Bio Investigative Site 0407 — Palo Alto
D3 Bio Investigative Site 0404 — Denver
D3 Bio Investigative Site 0406 — Sarasota
D3 Bio Investigative Site 0401 — Detroit
D3 Bio Investigative Site 0405 — Nashville
D3 Bio Investigative Site 0403 — Houston

Spain · 6 centers

D3 Bio Investigative Site 0706 — Barcelona
D3 Bio Investigative Site 0701 — Barcelona
D3 Bio Investigative Site 0704 — Madrid
D3 Bio Investigative Site 0705 — Madrid
D3 Bio Investigative Site 0703 — Valencia
D3 Bio Investigative Site 0702 — Valencia

Australia · 5 centers

D3 Bio Investigative Site 0102 — Sydney
D3 Bio Investigative Site 0101 — Malvern
D3 Bio Investigative Site 0105 — Melbourne
D3 Bio Investigative Site 0103 — Nedlands
D3 Bio Investigative Site 0104 — Bedford Park

Italy · 5 centers

D3 Bio Investigative Site 0905 — Candiolo
D3 Bio Investigative Site 0902 — Milan
D3 Bio Investigative Site 0904 — Naples
D3 Bio Investigative Site 0901 — Rome
D3 Bio Investigative Site 0903 — Siena

France · 4 centers

D3 Bio Investigative Site 0804 — Bordeaux
D3 Bio Investigative Site 0803 — Lyon
D3 Bio Investigative Site 0801 — Rennes
D3 Bio Investigative Site 0802 — Villejuif

South Korea · 4 centers

D3 Bio Investigative Site 0204 — Cheongju-si
D3 Bio Investigative Site 0202 — Seoul
D3 Bio Investigative Site 0203 — Seoul
D3 Bio Investigative Site 0201 — Seoul

Germany · 2 centers

D3 Bio Investigative Site 1003 — Cologne
D3 Bio Investigative Site 1002 — Hamburg

Japan · 2 centers

D3 Bio Investigative Site 0601 — Kashiwa
D3 Bio Investigative Site 0602 — Tokyo

Hong Kong · 1 center

D3 Bio Investigative Site 0501 — Shatin

Publications

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

Identifiers

NCT: NCT05410145 · D3S-001-100 · 2023-508517-16

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗