Neoadjuvant/Adjuvant Pembrolizumab Plus Chemotherapy

Phase 2

Active, not recruiting

• Conditions: Non Small Cell Lung Cancer; Immune Checkpoint Inhibitor; Neoadjuvant Therapy
• Interventions: Drug: Pembrolizumab

• Registration Number: NCT05383716
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

A phase II, single-arm, open-label study evaluating feasibility, safety and efficacy of combined chemotherapy and pembrolizumab as neoadjuvant/adjuvant therapy in stage IIa-IIIB NSCLC adult patients followed by adjuvant PD-(L)1 inhibitor treatment for up to 1 year

Detailed Description

Two to four cycles of neoadjuvant chemotherapy in combination with pembrolizumab will be administered before surgery, followed by another one to two cycles of chemotherapy plus pembrolizumab after surgery (4 cycles neoadjuvant/adjuvant chemotherapy in total ) then use pembrolizumab monotherapy for up to 1 year.

Study Timeline

• Study First Submitted: 2022-05-17
• Study First Submitted QC: 2022-05-17
• Study First Posted: 2022-05-20
• Study Start: 2022-07-01
• Primary Completion: 2023-12-08
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-22
• Last Update Posted: 2024-04-23
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Primary non-small cell lung cancer (NSCLC) confirmed by cytology or histology
2. Stage IIa to selected IIIb ( t1-4, n0-2 ) NSCLC according to the TNM stage (8th Edition) of IASLC, which is considered to be resectable;
3. At least one evaluable focus judged according to RECIST 1.1 standard (on spiral CT, the longest diameter of tumor should be at least 10 mm, the shortest diameter of metastasis lymphnode should be at least 20 mm)
4. ECOG PS 0 or 1
5. Adequate tumor samples available for gene detection (EGFR/ALK /ros1) with non-squamous and specimens for PD-L1 immunohistochemistry (IHC) in all the subjects.
6. Male or female, ≥ 18 years old
7. Adequate blood function: absolute neutrophil count (ANC) ≥ 2 × 109 / L, platelet count ≥ 100 × 109 / L and hemoglobin 110 ≥ 9 g / dl
8. Adequate liver function: total bilirubin ≤ upper limit of normal value (ULN); AST and alt ≤ upper limit of normal value (ULN); alkaline phosphatase ≤ upper limit of normal value (ULN)
9. Adequate renal function: serum creatinine ≤ upper limit of normal value (ULN) or calculated creatinine clearance ≥ 60ml / min
10. No history of using anti-tumor drug treatment before
11. For patients who have had previous surgery, it is required that more than 4 weeks have passed since the start of study treatment, and the patients have recovered
12. Sign the informed consent form (the informed consent form needs to be approved by the independent ethics committee, and the informed consent of the patient should be obtained before starting any substantive trial procedure)

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Exclusion Criteria

1. Carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene or other known targetable driver mutations.
2. Active, known or suspected autoimmune disease.
3. Other active malignancy in the last 5 years (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast).
4. Prior treatment with anti-PD-1, anti-CTLA-4 (cytotoxic T lymphocyte-associated antigen (CTLA-4), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
5. History of allergy to study drug components excipients
6. Having any uncontrolled systemic diseases, including active infection, uncontrolled hypertension, diabetes, unstable angina, congestive heart failure, acte myocardial infarction (within 3 months before treatment), serious arrhythmia requiring drug treatment, liver, kidney and metabolic diseases
7. Women in pregnancy or lactation

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
chemotherapy plus pembrolizumab	Pembrolizumab	Two to four cycles of neoadjuvant chemotherapy in combination with pembrolizumab will be administered before surgery, followed by another one to two cycles of chemotherapy plus pembrolizumab after surgery (4 cycles neoadjuvant/adjuvant chemotherapy in total ) then use pembrolizumab monotherapy for up to 1 year

Primary Outcome Measures

Name	Time	Method
MPR(major pathologic response)	Up to 8weeks	more than 90 percent decrease in viable tumor

Secondary Outcome Measures

Name	Time	Method
EFS (event free survival)	8 weeks	the time length from randomization (mainly from the receipt of pathology and genetic diagnosis reports)to any of the following events: disease progression, disease recurrence or death from any cause. Disease progression or relapse will be assessed according to RECIST 1.1
Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	8 weeks	Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to NCI-CTCAE V5.0
Complete pathological (CPR) response rate	8 weeks	The investigator assessed CPR rate was defined as the percentage of subjects who achieved complete pathological remission (no residual tumor in lung and lymph nodes)
OS (overall survival)	8 weeks	the time length from randomization (mainly from the receipt of pathology and genetic diagnosis reports)to death from any cause.
Evaluate tissue biomarkers	8 weeks	The goals for these analyses are for hypothesis generating. The results will need to be confirmed by future studies.; Used for hypothesis generating. Transcriptome analysis identity markers with efficacy and/or toxicity.

Trial Locations

Locations (1)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China