Study of D3S-002 as Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations

Study Overview
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Brief Summary
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This first-in-human (FIH) study aims to assess the safety, tolerability, pharmacokinetics, and recommended phase 2 dose (RP2D) of D3S-002 given orally daily for 21-day cycles in adult subjects with advanced solid tumors with mitogen-activated protein kinase (MAPK) pathway mutations.

Official Title
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A Phase 1, Open-label, Dose-escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Recommended Phase 2 Dose of D3S-002 Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations

Conditions
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Advanced Solid Tumors With MAPK Pathway Mutations

Intervention / Treatment
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* Drug: D3S-002


Participation Criteria
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Eligibility Criteria
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Inclusion: Subjects must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor with evidence of progressive disease. Subjects must have documented mitogen-activated protein kinase (MAPK) pathway mutation(s) within the last 5 years identified by a local test on tumor tissue or blood (eg, rat sarcoma (RAS), rapidly accelerated fibrosarcoma (RAF), and MAPK kinase (MAPKK) mutations). Subjects must be refractory to or intolerable with standard treatment, or have no available standard of care. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 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. Any concurrent chemotherapy, immunotherapy, targeted therapy, cell therapy, biologic or hormonal therapy and any medical devices for cancer treatment.

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-002<br>Dose Escalation, D3S-002 administered orally. | Drug: D3S-002<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) |  | 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-002 maximum observed plasma concentration (Cmax) |  | First dose up to 24 months | 
| D3S-002 time to maximum plasma concentration (tmax) |  | First dose up to 24 months | 
| D3S-002 half-life (t1/2) |  | First dose up to 24 months | 
| D3S-002 area under the concentration-time curve (AUC) |  | First dose 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) |  | Until disease progression or end of treatment (up to approximately 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) |  | Until disease progression or end of treatment (up to approximately 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) |  | Until disease progression or end of treatment (up to approximately 24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors, mitogen-activated protein kinase, mutation