IN10018 plus D-1553 versus anti-PD-1 and chemotherapy for first-line KRAS G12C non-squamous NSCLC

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

This trial tests whether taking IN10018 with D-1553 works better than standard anti‑PD‑1 plus platinum and pemetrexed for people with newly diagnosed, advanced non‑squamous NSCLC that has a KRAS G12C mutation.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: InxMed (Shanghai) Co., Ltd. (Industry-sponsored)
• Locations: 11 sites (Beijing, Beijing Municipality and 10 other locations)
• Trial ID: NCT07174908 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label Phase 3 trial comparing the combination of IN10018 and D‑1553 to standard first‑line anti‑PD‑1 therapy plus platinum and pemetrexed in patients with untreated, locally advanced or metastatic non‑squamous NSCLC harboring KRAS G12C. Patients must have centrally confirmed KRAS G12C mutation, measurable disease, and ECOG 0–1 to enroll. The investigational combination is supported by preclinical data suggesting synergistic antitumor effects through FAK‑YAP pathway suppression, reduced stromal fibrosis, and induction of immunogenic cell death, and by early-phase clinical signals of activity and tolerability. Primary outcomes will focus on efficacy and safety compared with current standard chemo‑immunotherapy.

Who should consider this trial

Good fit: Adults 18–80 with histologically confirmed, treatment‑naive locally advanced or metastatic non‑squamous NSCLC, centrally confirmed KRAS G12C mutation, at least one measurable lesion, ECOG 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients with other driver mutations, prior KRAS G12C/FAK/immune checkpoint inhibitor therapy, active untreated brain metastases, or poor performance status (ECOG >1) are unlikely to qualify or benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could offer longer disease control or survival than current first‑line chemo‑immunotherapy for patients with KRAS G12C non‑squamous NSCLC.

How similar studies have performed: Early‑phase studies of IN10018 plus D‑1553 have shown promising antitumor activity and tolerability and approved KRAS G12C inhibitors have clinical benefit, but a head‑to‑head Phase 3 comparison against standard chemo‑immunotherapy in the first‑line setting is novel.

Eligibility criteria

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

Where this trial is running

Beijing, Beijing Municipality and 10 other locations

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (Recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Union Hospital Tongji Medidcal College Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Jiangsu Cancer Hospital — Nanjing, Jiangsu, China (Recruiting)
• First Affiliated Hospital of Gannan Medical University — Gannan, Jiangxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Zhengbo Song Professor, Doctor — Zhejiang Cancer Hospital
• Study coordinator: Shu Fang Project Manager, bachelor

Conditions Non-Small Cell Lung Cancer