A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Non-Small Cell Lung Cancer

Официальное название

A Phase 2, Open-label Study of VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor, in Patients With Previously Treated, Advanced KRAS G12D-Mutated Non-Small Cell Lung Cancer (TARGET-D 202)

Обзор

This study will assess the safety and efficacy of VS-7375 alone and in combination with cetuximab in patients with metastatic KRAS G12D - mutated Non-Small Cell Lung Cancer

Вмешательства

• Препарат VS-7375
  Taken by mouth

Первичные конечные точки

• Confirmed ORR by blinded independent central review (BICR) per RESIST v1.1 [Срок оценки: 6 months]
• To characterize the safety and tolerability of VS-7375 monotherapy administered on a daily oral schedule in participants with KRAS G12D-mutated NSCLC [Срок оценки: 6 months]

Вторичные конечные точки (6)

• Confirmed ORR per RECIST v1.1 assessed by BICR (primary) and Investigator (secondary) assessments [Срок оценки: 24 months]
• Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, Cmax [Срок оценки: 20 weeks]
• Plasma Pharmacokinetics (PK) of VS-7375 and relevant metabolites, AUC [Срок оценки: 20 weeks]
• To evaluate Pharmacodynamics (PD) and other relevant blood tumor markers specific to tumor type [Срок оценки: Up to 2.5 years]
• To assess the health-related quality of life and disease based on European Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire Core module C30 (QLQ-C30) [Срок оценки: 24 months]
• Time to next therapy [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Histopathology confirmed unresectable locally advanced or metastatic NSCLC
• Measurable disease per RECIST 1.1
• Local testing confirmed KRAS G12D mutation (tissue required for confirmatory central testing)
• ECOG PS=0 or 1
• Adequate organ function
• Received prior treatment with a platinum-based chemotherapy regimen and an immune checkpoint inhibitor in the advanced, non-resectable setting.
• Have documented disease progression during or following their most recent prior line of therapy.

Patients with 2L/3L on stable or preferred dose:

• Received at least 1 and no more than 2 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.

Patients with 2L-4L with brain metastases:

• Received at least 1 and no more than 3 prior systemic lines of therapy for advanced (in the unresectable locally advanced or metastatic setting) NSCLC.
• Have asymptomatic and untreated brain metastases
• At least 1 untreated measurable brain lesion per mRECIST v1.1 with a long axis ≥ 0.5 cm and ≤ 3 cm.

Критерии исключения

• Have any other documented co-existing common RAS mutation(s)
• Prior anti-cancer Tx within 4 weeks or drug-specific timeline within first treatment dose, whichever shorter
• Major surgery within 4 weeks of first treatment dose
• Radiation therapy (RT) within 1 week of first treatment dose
• History of drug-induced Interstitial Lung Disease
• Receipt of prior direct RAS inhibitor
• Untreated or symptomatic CNS metastasis
• Receipt of strong CYP3A4 inhibitor/inducer or CYP3A4 sensitive substrates with narrow therapeutic index within 14 days or drug-specific timeline within first treatment dose, whichever is shorter
• Receipt of PPI or H2 blocker within 5 days
• Inability to swallow oral medication
• Other protocol-defined 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

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 3 центра

• START LA — Los Angeles
• START New Jersey — East Brunswick
• START Fort Worth — Fort Worth

Идентификаторы

NCT: NCT07659782 · VS-7375-202 · 2026-526472-23-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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