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

Study Overview
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Brief Summary
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This first-in-human (FIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of D3S-001 and identify the recommended Phase 2 dose (RP2D) when D3S-001 is administered as monotherapy to subjects with advanced solid tumors with the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) p.G12C mutation.

Official Title
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A Phase 1, Open-label, Dose-escalation and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-001 Monotherapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation

Conditions
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KRAS P.G12C

Intervention / Treatment
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* Drug: D3S-001


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: D3S-001<br>Dose Escalation, D3S-001 administered orally. Dose Expansion, D3S-001 administered orally in selected cancer type patients. | Drug: D3S-001<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS p.G12C, Mutation, advanced solid tumors