A Phase 3 Study of IN10018 in Combination With D-1553 Versus Standard Therapy for First Line Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation

Официальное название

A Phase 3 Multicenter, Randomized, Controlled, and Open-Label Study of IN10018 in Combination With D-1553 Versus Standard Therapy for the Treatment of First Line Locally-advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation

Обзор

This is a multicenter, randomized, open-label, phase III clinical study, to evaluate the efficacy and safety of IN10018 in combination with D-1553 as compared to anti-PD-1 monoclonal antibody (mAb) in combination with platinum and pemetrexed as the first-line treatment for the locally advanced or metastatic KRASG12C mutation-positive non-squamous non-small cell lung cancer (NSCLC).

Подробное описание

Preclinical studies indicate that IN10018 synergizes with D-1553 to enhance antitumor activity and delay resistance through multiple mechanisms, including suppression of FAK-YAP signaling pathway activation, reduction of tumor stromal fibrosis, and induction of immunogenic cell death (ICD). IN10018-602/D1553-106 is an ongoing Phase Ib/II clinical study evaluating the synergistic antitumor activity and safety of IN10018 combined with D-1553 in patients with KRAS G12C-mutant solid tumors. Preliminary results have demonstrated notable antitumor activity and a favorable safety and tolerability profile in patients with advanced KRAS G12C-mutant NSCLC and metastatic colorectal cancer. Based on the available clinical data, the sponsor plans to initiate a Phase III study in previously untreated patients with advanced KRAS G12C-mutant NSCLC to further evaluate the efficacy and safety of IN10018 in combination with D-1553 compared with first-line standard treatment.

Вмешательства

• Препарат IN10018 in combination with D-1553
  IN10018 100mg QD PO and D-1553 600mg BID PO, 21days per cycle
• Препарат anti-PD-1 monoclonal antibody in combination with platinum and pemetrexed
  Tislelizumab 200mg Q3W IV + Carboplatin AUC 5 mg/mL/min or Cisplatin 75mg/m² Q3W IV+ Pemetrexed 500mg/m² Q3W IV

Первичные конечные точки

• Progression-Free Survival (PFS) [Срок оценки: up to 36 months]

Вторичные конечные точки (9)

• Objective Response Rate (ORR) [Срок оценки: up to 36 months]
• Overall Survival (OS) [Срок оценки: up to 60 months]
• Disease Control Rate (DCR) [Срок оценки: Up to 36 months]
• Duration of Response (DoR) [Срок оценки: up to 36 months]
• PFS [Срок оценки: up to 36 months]
• ORR [Срок оценки: up to 36 months]
• DCR [Срок оценки: up to 36 months]
• DOR [Срок оценки: Up to 36 months]
• Number of subjects with adverse event [Срок оценки: up to 36 months]

Критерии участия

Критерии включения

• Able and willing to provide informed consent and comply with study requirements
• Has histologically confirmed locally advanced (Stage IIIB/C) or metastatic (Stage IV) non-squamous NSCLC
• Aged 18-80 years at the time of consent
• Has KRAS G12C mutation confirmed by central laboratory
• Has not received prior systemic therapy for advanced or metastatic NSCLC
• Has at least one measurable lesion per RECIST v1.1
• ECOG performance status of 0-1
• Has adequate organ function
• Life expectancy ≥3 months in the opinion of the Investigator
• Male and female subjects of reproductive potential must agree to use effective contraception during and for 6 months after treatment

Критерии исключения

• Has other histological subtypes of NSCLC (e.g., small cell or neuroendocrine)
• Has active or untreated CNS metastases or carcinomatous meningitis
• Prior treatment with KRAS G12C inhibitors, FAK inhibitors, or immune checkpoint inhibitors
• Has another known driver mutation with approved targeted therapy (e.g., EGFR, ALK, ROS1)
• Has uncontrolled cardiovascular disease, active severe infection, interstitial lung disease, or autoimmune disease requiring systemic therapy
• Has history of another malignancy within 5 years, except those curatively treated and considered low risk (e.g., basal cell carcinoma, cervical carcinoma in situ)
• Has gastrointestinal conditions that may interfere with absorption of oral drugs (if applicable)
• Has known active hepatitis B, hepatitis C, or HIV infection
• Has received a live vaccine within 30 days before first dose of study drug
• Pregnant or breastfeeding women
• Has psychiatric or substance abuse disorders that would interfere with study compliance
• Is participating in another interventional clinical study
• Any condition that, in the opinion of the Investigator, would interfere with participation or study results

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 11 центров

• Beijing Cancer Hospital — Пекин
• The First Affiliated Hospital, Sun Yat-sen University — Гуанчжоу
• Henan Cancer Hospital — Чжэнчжоу
• The First Affiliated Hospital of Zhengzhou University — Чжэнчжоу
• Union Hospital Tongji Medidcal College Huazhong University of Science and Technology — Ухань
• Hunan Cancer Hospital — Чанша
• Jiangsu Cancer Hospital — Нанкин
• First Affiliated Hospital of Gannan Medical University — Gannan
• … и ещё 3 центра

Публикации

• Song Z, Li X, Lin R, Shi H, Yuan Y, Liu Y, Luo Y, Lv T, Zhang Y, Zhu L, Zhu Y, Zhang L, Wang Z. Ifebemtinib plus garsorasib as first-line treatment for KRASG12C-mutated non-small-cell lung cancer in China: a multicentre, single-arm expansion cohort from a phase 1b/2 trial. Lancet Respir Med. 2026 Jul 7:S2213-2600(26)00142-6. doi: 10.1016/S2213-2600(26)00142-6. Online ahead of print. PMID 42413526

Идентификаторы

NCT: NCT07174908 · IN10018-023

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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