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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат D3S-001
  Oral
• Препарат Pembrolizumab
  Intravenous
• Препарат Cisplatin
  Intravenous
• Препарат Carboplatin
  Intravenous
• Препарат Pemetrexed
  Intravenous
• Препарат Cetuximab
  Intravenous

Первичные конечные точки

• Number of Participants With Adverse Events (AEs) [Срок оценки: From first dose until 30 days after the last dose (or specified in the protocol).]
• Number of Participants With Dose-Limiting Toxicities (DLTs) [Срок оценки: From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.]

Вторичные конечные точки (8)

• D3S-001 maximum observed plasma concentration (Cmax) [Срок оценки: Up to 24 months.]
• D3S-001 time to maximum plasma concentration (tmax) [Срок оценки: Up to 24 months.]
• D3S-001 half-life (t1/2) [Срок оценки: Up to 24 months.]
• D3S-001 area under the concentration-time curve (AUC) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: Up to 24 months.]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 16 центров

• D3 Bio Investigative Site 0303 — Пекин
• D3 Bio Investigative Site 0306 — Гуанчжоу
• D3 Bio Investigative Site 0305 — Ханчжоу
• D3 Bio Investigative Site 0307 — Харбин
• D3 Bio Investigative Site 0309 — Ухань
• D3 Bio Investigative Site 0312 — Ухань
• D3 Bio Investigative Site 0304 — Nanchang
• D3 Bio Investigative Site 0302 — Шэньян
• … и ещё 8 центров

США · 7 центров

• D3 Bio Investigative Site 0402 — Orange
• D3 Bio Investigative Site 0407 — Palo Alto
• D3 Bio Investigative Site 0404 — Denver
• D3 Bio Investigative Site 0406 — Sarasota
• D3 Bio Investigative Site 0401 — Detroit
• D3 Bio Investigative Site 0405 — Nashville
• D3 Bio Investigative Site 0403 — Houston

Испания · 6 центров

• D3 Bio Investigative Site 0706 — Barcelona
• D3 Bio Investigative Site 0701 — Barcelona
• D3 Bio Investigative Site 0704 — Madrid
• D3 Bio Investigative Site 0705 — Madrid
• D3 Bio Investigative Site 0703 — Valencia
• D3 Bio Investigative Site 0702 — Valencia

Австралия · 5 центров

• D3 Bio Investigative Site 0102 — Sydney
• D3 Bio Investigative Site 0101 — Malvern
• D3 Bio Investigative Site 0105 — Melbourne
• D3 Bio Investigative Site 0103 — Nedlands
• D3 Bio Investigative Site 0104 — Bedford Park

Италия · 5 центров

• D3 Bio Investigative Site 0905 — Candiolo
• D3 Bio Investigative Site 0902 — Milan
• D3 Bio Investigative Site 0904 — Naples
• D3 Bio Investigative Site 0901 — Rome
• D3 Bio Investigative Site 0903 — Siena

Франция · 4 центра

• D3 Bio Investigative Site 0804 — Bordeaux
• D3 Bio Investigative Site 0803 — Lyon
• D3 Bio Investigative Site 0801 — Rennes
• D3 Bio Investigative Site 0802 — Villejuif

South Korea · 4 центра

• D3 Bio Investigative Site 0204 — Cheongju-si
• D3 Bio Investigative Site 0202 — Seoul
• D3 Bio Investigative Site 0203 — Seoul
• D3 Bio Investigative Site 0201 — Seoul

Германия · 2 центра

• D3 Bio Investigative Site 1003 — Cologne
• D3 Bio Investigative Site 1002 — Hamburg

Япония · 2 центра

• D3 Bio Investigative Site 0601 — Kashiwa
• D3 Bio Investigative Site 0602 — Tokyo

Гонконг · 1 центр

• D3 Bio Investigative Site 0501 — Shatin

Публикации

• 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. PMID 40301557

Идентификаторы

NCT: NCT05410145 · D3S-001-100 · 2023-508517-16

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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