KRAS P.G12C
Conditions
Keywords
KRAS p.G12C, Mutation, advanced solid tumors
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.
Interventions
DRUGD3S-001
Oral
DRUGPembrolizumab
Intravenous
DRUGCisplatin
Intravenous
DRUGCarboplatin
Intravenous
DRUGPemetrexed
Intravenous
DRUGCetuximab
Intravenous
Sponsors
D3 Bio (Wuxi) Co., Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
| 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. |
| 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. |
Countries
Australia, China, France, Germany, Hong Kong, Italy, Japan, South Korea, Spain, United States
Contacts
CONTACTMedical Director
STUDY_DIRECTORCheng Chen, MD
D3 Bio (Wuxi) Co., Ltd
Outcome results
None listed