Non-Small Cell Lung Cancer
Conditions
Brief summary
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
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.
Interventions
DRUGIN10018 in combination with D-1553
IN10018 100mg QD PO and D-1553 600mg BID PO, 21days per cycle
DRUGanti-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
Sponsors
InxMed (Shanghai) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | up to 36 months | Defined as time from randomization until disease progression or death from any cause, whichever occurs first assessed per RECIST v1.1 by blinded independent central review (BICR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | up to 36 months | Defined as complete response (PR) + partial response (PR) assessed per RECIST v1.1 by BICR |
| Overall Survival (OS) | up to 60 months | Defined as time from randomization to death by any cause |
| Disease Control Rate (DCR) | Up to 36 months | Defined as ORR + stable disease (SD) assessed per RECIST v1.1 by BICR |
| Duration of Response (DoR) | up to 36 months | Defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first. assessed per RECIST v1.1 by BICR |
| PFS | up to 36 months | Defined as time from randomization until disease progression or death from any cause, whichever occurs first assessed per RECIST v1.1 by investigator assessment. |
| ORR | up to 36 months | defined as CR+PR assessed per RECIST v1.1 by investigators |
| DCR | up to 36 months | Defined as ORR + stable disease (SD) assessed per RECIST v1.1 by investigators |
| DOR | Up to 36 months | Defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first. assessed per RECIST v1.1 by investigators |
| Number of subjects with adverse event | up to 36 months | The number of subjects who experienced AEs is presented |
Countries
China
Contacts
CONTACTShu Fang Project Manager, bachelor
CONTACTJack Zhang Clinical Trial Manager, bachelor
PRINCIPAL_INVESTIGATORZhengbo Song Professor, Doctor
Zhejiang Cancer Hospital
PRINCIPAL_INVESTIGATORShun Lu Professor, Doctor
Shanghai Chest Hospital
Outcome results
None listed