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

Phase 1

Recruiting

• Conditions: KRAS P.G12C
• Interventions: Drug: D3S-001; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Cetuximab; Drug: Carboplatin; Drug: Pemetrexed

• Registration Number: NCT05410145
• Lead Sponsor: D3 Bio (Wuxi) Co., Ltd

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-25
• Study First Submitted QC: 2022-06-06
• Study First Posted: 2022-06-08
• Study Start: 2022-08-03
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-24
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 392

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
D3S-001 monotherapy	D3S-001	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.
D3S-001 and Cetuximab	D3S-001	Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cetuximab administered intravenously.
D3S-001 and pembrolizumab	D3S-001	Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Pembrolizumab administered intravenously.
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed)	D3S-001	Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + permetrexed administered intravenously
D3S-001 and pembrolizumab	Pembrolizumab	Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Pembrolizumab administered intravenously.
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed)	Carboplatin	Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + permetrexed administered intravenously
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed)	Cisplatin	Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + permetrexed administered intravenously
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + permetrexed)	Pemetrexed	Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cisplatin + pemetrexed administered intravenously or Carboplatin + permetrexed administered intravenously
D3S-001 and Cetuximab	Cetuximab	Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients. Cetuximab administered intravenously.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
D3S-001 half-life (t1/2)	Up to 24 months.
D3S-001 area under the concentration-time curve (AUC)	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)	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)	Up to 24 months.
D3S-001 maximum observed plasma concentration (Cmax)	Up to 24 months.
D3S-001 time to maximum plasma concentration (tmax)	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)	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.

Trial Locations

Locations (1)

D3 Bio Investigative Site; 🇪🇸 Valencia, Spain