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

InxMed

Status and phase: Enrolling; Phase 3

Conditions: Non-Small Cell Lung Cancer

Treatments: Drug: anti-PD-1 monoclonal antibody in combination with platinum and pemetrexed; Drug: IN10018 in combination with D-1553

Study type: Interventional

Funder types: Industry

Identifiers

NCT07174908

IN10018-023

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

IN10018 plus D-1553

Experimental group

Description:

Subjects receive IN10018 100mg orally once daily (QD) and D-1553 600mg orally twice daily (BID) on Days 1-21 of each 21-day cycle, until disease progression or unacceptable toxicity.

Treatment:

Drug: IN10018 in combination with D-1553

Tislelizumab plus Platinum and Pemetrexed

Active Comparator group

Description:

Subjects receive Tislelizumab 200mg intravenously (IV) once every 3 weeks (Q3W) until disease progression, plus Carboplatin (AUC = 5 mg/mL/min, Q3W, IV) or Cisplatin (75 mg/m², Q3W, IV) for up to 4 cycles, in combination with Pemetrexed (500 mg/m², Q3W, IV) until disease progression.

Treatment:

Drug: anti-PD-1 monoclonal antibody in combination with platinum and pemetrexed