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
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
Study locations (7)
D3 Bio Investigative Site 0402
Orange, California, 92868
D3 Bio Investigative Site 0407
Palo Alto, California, 94304-2205
D3 Bio Investigative Site 0404
Denver, Colorado, 80218-1238
D3 Bio Investigative Site 0406
Sarasota, Florida, 34232-6410
D3 Bio Investigative Site 0401
Detroit, Michigan, 48202-2608
D3 Bio Investigative Site 0405
Nashville, Tennessee, 37203
D3 Bio Investigative Site 0403
Houston, Texas, 77030
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)