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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
400
IN10018 100mg QD PO and D-1553 600mg BID PO, 21days per cycle
Tislelizumab 200mg Q3W IV + Carboplatin AUC 5 mg/mL/min or Cisplatin 75mg/m² Q3W IV+ Pemetrexed 500mg/m² Q3W IV
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGThe First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
RECRUITINGUnion Hospital Tongji Medidcal College Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
NOT_YET_RECRUITINGJiangsu Cancer Hospital
Nanjing, Jiangsu, China
RECRUITINGFirst Affiliated Hospital of Gannan Medical University
Gannan, Jiangxi, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
NOT_YET_RECRUITINGShanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITING...and 1 more locations
Progression-Free Survival (PFS)
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).
Time frame: up to 36 months
Objective Response Rate (ORR)
Defined as complete response (PR) + partial response (PR) assessed per RECIST v1.1 by BICR
Time frame: up to 36 months
Overall Survival (OS)
Defined as time from randomization to death by any cause
Time frame: up to 60 months
Disease Control Rate (DCR)
Defined as ORR + stable disease (SD) assessed per RECIST v1.1 by BICR
Time frame: Up to 36 months
Duration of Response (DoR)
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
Time frame: up to 36 months
PFS
Defined as time from randomization until disease progression or death from any cause, whichever occurs first assessed per RECIST v1.1 by investigator assessment.
Time frame: up to 36 months
ORR
defined as CR+PR assessed per RECIST v1.1 by investigators
Time frame: up to 36 months
DCR
Defined as ORR + stable disease (SD) assessed per RECIST v1.1 by investigators
Time frame: up to 36 months
DOR
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
Time frame: Up to 36 months
Number of subjects with adverse event
The number of subjects who experienced AEs is presented
Time frame: up to 36 months
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