KRAS P.G12D
Conditions
Keywords
KRAS P.G12D Mutation, Advanced solid tumors
Brief summary
This is a first-in-human (FIH) multicenter, open-label, dose-escalation Phase 1 clinical trial to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of D3S-003 in participants with advanced KRAS p.G12D mutant solid tumors.
Interventions
DRUGD3S-003
Oral Tablet
Sponsors
D3 Bio (Wuxi) Co., Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must have histologically confirmed locally advanced, recurrent, or metastatic malignancy that has failed to respond to adequate standard treatment(s), or for which no effective standard treatment is available. * Subjects must have documented presence of KRAS p.G12D mutation by a local test identified through tumor tissue or blood collected within the last 5 years. * Subjects 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 criteria
* Participant has any prior treatment with a specific KRAS G12D inhibitor/degrader or pan RAS inhibitor/degrader. * Subject has uncontrolled intercurrent illness, including but not limited to serious chronic gastrointestinal conditions associated with diarrhea, ongoing or active infections, uncontrolled or significant cardiovascular disease, autoimmune or inflammatory disorders or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring adverse events (AEs), or compromise the ability of the subject to give written consent. * Uncontrolled or untreated brain metastases * Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy NOTE: Other protocol inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Dose-Limiting Toxicities (DLTs) | From Cycle 1 Day 1 through Day 21. Each cycle is 21 days. |
| Number of Participants with Adverse Events (AEs) | From screening visit until 30 days after the last dose (or specified in the protocol) |
| Maximum tolerated dose (MTD) based on dose limiting toxicities (DLTs) | First dose up to 7 months |
| Phase 2 dose (RP2D) | First dose up to 7 months |
Secondary
| Measure | Time frame |
|---|---|
| D3S-003 concentration of drug immediately before the administration of next dose (Ctrough) | First dose up to 7 months |
| D3S-003 maximum observed plasma concentration (Cmax) | First dose up to 7 months |
| D3S-003 time to maximum plasma concentration (tmax) | First dose up to 7 months |
| D3S-003 half-life (t1/2) | First dose up to 7 months |
| D3S-003 area under the concentration-time curve (AUC) | First dose up to 7 months |
| Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Until disease progression or end of treatment (up to approximately 7 months) |
| Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Until disease progression or end of treatment (up to approximately 7 months) |
| Disease Control Rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Until disease progression or end of treatment (up to approximately 7 months) |
| Progression-free survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) | Until disease progression or end of treatment (up to approximately 7 months) |
Countries
Australia, South Korea, United States
Contacts
CONTACTMedical Director
Outcome results
None listed