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

NCT ID: NCT07174908

Last Updated: 2026-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-09-10

Study Completion Date

2030-09-30

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Non-Small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IN10018 plus D-1553

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.

Group Type EXPERIMENTAL

IN10018 in combination with D-1553

Intervention Type DRUG

IN10018 100mg QD PO and D-1553 600mg BID PO, 21days per cycle

Tislelizumab plus Platinum and Pemetrexed

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.

Group Type ACTIVE_COMPARATOR

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

Intervention Type DRUG

Tislelizumab 200mg Q3W IV + Carboplatin AUC 5 mg/mL/min or Cisplatin 75mg/m² Q3W IV+ Pemetrexed 500mg/m² Q3W IV

Interventions

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IN10018 in combination with D-1553

IN10018 100mg QD PO and D-1553 600mg BID PO, 21days per cycle

Intervention Type DRUG

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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InxMed (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zhengbo Song Professor, Doctor

Role: PRINCIPAL_INVESTIGATOR

Zhejiang Cancer Hospital

Shun Lu Professor, Doctor

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital

Locations

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Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

Union Hospital Tongji Medidcal College Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status NOT_YET_RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

First Affiliated Hospital of Gannan Medical University

Gannan, Jiangxi, China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status NOT_YET_RECRUITING

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Shu Fang Project Manager, bachelor

Role: CONTACT

86-15933968623

Jack Zhang Clinical Trial Manager, bachelor

Role: CONTACT

Facility Contacts

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Jun Zhao Chief Physician, MD

Role: primary

86-13521469355

Kejing Tang Chief Physician, MD

Role: primary

86-13802946566

Huijuan Wang Chief Physician, MD

Role: primary

86-18638561588

Sanxing Guo Chief Physician, MD

Role: primary

86-18337128112

Ruiguang Zhang Associate Chief Physician, MD

Role: primary

86-15071116896

Xiaorong Dong Chief Physician, MD

Role: backup

Yongzhong Luo Chief Physician, MD

Role: primary

86-13607443876

Bo Shen Chief Physician, MD

Role: primary

86-13913910555

Huaqiu Shi Chief Physician, BS

Role: primary

86-13576666365

Longhua Sun Chief Physician, MD

Role: primary

86-18279110112

Shun Lu Chief Physician, MD

Role: primary

86-13857153345

Yongfeng Yu Chief Physician, MD

Role: backup

Zhengbo Song Chief Physician, MD

Role: primary

86-13857153345

Other Identifiers

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IN10018-023

Identifier Type: -

Identifier Source: org_study_id

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