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This is a randomized, open-label, multicenter phase II study. The trial plans to enroll 164 subjects with resectable stage IIA-IIIB (N2) NSCLC. Participants will be randomized 1:1 into either the ivonescimab plus chemotherapy or penpulimab plus chemotherapy treatment arm. After 3-4 cycles of neoadjuvant therapy, surgical resection will be performed. The primary objective is to compare the pathological complete response (pCR) rate assessed by local pathologists between ivonescimab-based and penpulimab-based chemo-immunotherapy regimens in the neoadjuvant treatment of resectable NSCLC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ivonescimab+Chemo | Experimental | Ivonescimab (AK112) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. |
|
| Penpulimab+Chemo | Active Comparator | Penpulimab (AK105) + platinum-based doublet chemotherapy as neoadjuvant treatment, administered every 3 weeks (Q3W) for 3-4 cycles. Surgical resection should be performed 4-6 weeks after the last dose, followed by safety follow-up and survival surveillance. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ivonescimab+Chemo | Drug | Ivonescimab (AK112) + platinum-based doublet chemotherapy |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic Complete Response (pCR) Rate | Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens. | Within 1 month after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Major Pathologic Response (MPR) Rate | Major pathologic response (MPR) rate is defined as the percentage of participants with less than 10% of residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens. Viable tumors in situ carcinoma should not be included in MPR calculation. | Within 1 month after surgery |
| Measure | Description | Time Frame |
|---|---|---|
| Deep pathologic response (DPR) rate | Deep pathologic response (DPR) rate is defined as the percentage of participants with less than 5% of residual viable tumor in lung primary or lymph nodes as evaluated by systematic pathological review of surgical specimens. Viable tumors in situ carcinoma should not be included in DPR calculation. | Within 1 month after surgery |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University People's Hospital | Beijing | Beijing Municipality | 100000 | China | ||
| Hunan Cancer Hospital |
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| Penpulimab+Chemo |
| Drug |
Penpulimab (AK105) + platinum-based doublet chemotherapy |
|
| Event-Free Survival (EFS) | Defined as the time from the first dose to the occurrence of any of the following events (whichever occurs first), assessed in the Intention-To-Treat (ITT) population: Disease progression (based on RECIST v1.1 criteria by investigators); Local recurrence or distant metastasis; Death from any cause | the time from the first dose to the occurrence of any of the following events (whichever occurs first), assessed in the Intention-To-Treat (ITT) population: Disease progression (based on RECIST v1.1 criteria by investigators); Local recurrence or dist |
| Objective response rate(ORR) | Preoperative radiological evaluation (as assessed by the investigator according to RECIST v1.1) of the number of complete or partial responses as a proportion of the population in the cohort. | Within 1 month after surgery |
| Overall Survival (OS) | Defined as the time from the date of randomization to the date of death due to any cause in the Intention-To-Treat (ITT) population. | The time from the date of randomization to the date of death due to any cause |
| 2-Year/3-year EFS rate | Defined as the proportion of patients without EFS events at 2 and 3 years after randomization estimated using the Kaplan-Meier method | At 2 and 3 years after randomization |
| Incidence of Adverse Events | AE captured by CTCAE 5.0 | up to 1 month post surgery |
| Changsha |
| Hunan |
| China |
| Shanghai Chest Hospital | Shanghai | Shanghai Municipality | China |
| The First Affiliated Hospital of Xi'an Jiaotong University | Xi’an | Shanxi | China |
| Second Affiliated Hospital, School of Medicine, Zhejiang University | Hangzhou | Zhejiang | China |