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

D3 Bio (Wuxi)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: KRAS P.G12C

Treatments: Drug: Pemetrexed; Drug: Cisplatin; Drug: Pembrolizumab; Drug: Cetuximab; Drug: D3S-001; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05410145

D3S-001-100

2023-508517-16 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 442 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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442 participants in 4 patient groups

D3S-001 monotherapy

Experimental group

Description:

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.

Treatment:

Drug: D3S-001

D3S-001 and pembrolizumab

Experimental group

Description:

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

Treatment:

Drug: D3S-001

Drug: Pembrolizumab

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

Experimental group

Description:

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

Treatment:

Drug: Carboplatin

Drug: D3S-001

Drug: Pemetrexed

Drug: Cisplatin

D3S-001 and Cetuximab

Experimental group

Description:

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

Treatment:

Drug: D3S-001

Drug: Cetuximab