Efficacy of PD-1 Inhibitor Combination Therapy in Non-small Cell Lung Cancer Patients Who Have Not Achieved Major Pathologic Response After Neoadjuvant Immunotherapy: a Multicenter, Phase II Clinical Trial

Phase 2

Not yet recruiting

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: LM-108+Sintilimab; Drug: IBI310+Sintilimab; Drug: IBI363; Drug: Sintilimab

• Registration Number: NCT06620822
• Lead Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

Brief Summary

Exploring the efficacy of PD-1 inhibitor combination therapy strategies for adjuvant therapy in a population that has not achieved major pathological regression after neoadjuvant immunotherapy for non-small cell lung cancer: a multicenter, phase II clinical study

Detailed Description

This study explores the potential resistance problem in patients with low response rates after neoadjuvant ICIs treatment by addressing their potential resistance problems through an adjuvant immune combination regimen of ICIs, with the aim of providing a personalized choice of perioperative regimens for patients with early stage II-III resectable NSCLC, and to reduce the risk of postoperative recurrence and death in patients.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-28
• Study First Submitted QC: 2024-09-28
• Last Update Submitted: 2024-09-28
• Study Start: 2024-09-30
• Study First Posted: 2024-10-01
• Last Update Posted: 2024-10-01
• Primary Completion: 2026-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 296

Inclusion Criteria

1. Subjects ≥ 18 years of age on the day of signed informed consent, male or female, and willing to follow study procedures;
2. ECOG score of 0 ~ 1;
3. Patients with resectable clinical stage II-IIIB (N2 only) NSCLC prior to neoadjuvant as assessed by the investigator (AJCC 8th ed.) and who are receiving 3 to 4 courses of standard PD-1 monoclonal antibody in combination with chemotherapy (platinum-containing two-agent chemotherapy) as neoadjuvant therapy during the neoadjuvant phase
4. Pathological evaluation of tumor for MPR (less than 10% residual tumor cells from the primary tumor) and specific remission rate (1 - residual tumor/primary tumor)
5. Subjects must have had complete resection of the NSCLC (no residual tumor and all surgical margins negative)
6. Histologically or cytologically confirmed squamous or non-squamous NSCLC.

Exclusion Criteria

1. Subjects who have undergone segmental lung resection or wedge resection only, and subjects who have not undergone systemic or lobe-specific lymph node dissection;
2. Postoperative treatment with off-protocol antitumor therapy (e.g., radiotherapy, chemotherapy, targeted therapy, other immunotherapies, etc.; antitumor herbal therapies require a 2-week washout period);
3. Severe grade 3 or higher irAE or severe organ damage during neoadjuvant immunotherapy;
4. Previous history of allogeneic bone marrow or organ transplantation;
5. Previous or current interstitial pneumonitis/lung disease requiring systemic hormone therapy;
6. Uncontrolled hypertension (blood pressure ≥150/90 mmHg at rest), with antihypertensive medications maintained at a stable dose for 7 days prior to the first dose of study drug;
7. Combination of other malignant tumors within 5 years prior to the first dose of study drug that require active treatment, except for tumors cured in the opinion of the investigator;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LM-108+Sintilimab	LM-108+Sintilimab	-
IBI310+Sintilimab	IBI310+Sintilimab	-
IBI363	IBI363	-
Sintilimab	Sintilimab	-

Primary Outcome Measures

Name	Time	Method
2-year DFS rate	2 years	2-year DFS rate for Non-MPR treatment groups: DFS is defined as the time from surgery to tumor recurrence or death from any cause (whichever occurs first). 2-year DFS rate is defined as the probability of remaining free of disease recurrence or death at the 2-year time point.

Secondary Outcome Measures

Name	Time	Method
2-year OS rate	2 years	2-year OS rate in the Non-MPR treatment groups: OS is defined as the time from the start of surgery to death from any cause. 2-year OS rate is defined as the probability of remaining free of death from any cause at the 2-year time point;
safety	2 years	Safety assessment: incidence and severity of AE (graded according to CTCAE v5.0), severity, and its relationship to the trial treatment; any laboratory tests, abnormal vital signs and physical examination findings, etc.

Trial Locations

Locations (1)

Shanghai Pulmonary Hospital; 🇨🇳 Shanghai, Shanghai, China