Neoadjuvant/Adjuvant Pembrolizumab Plus Chemotherapy (NeoP)

A Prospective, Single-arm PhaseⅡTrial of Neoadjuvant/Adjuvant Pembrolizumab Plus Platinum-doublet Chemotherapy (Chemo) in IIa-IIIb NSCLC

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

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Cancer; Neoadjuvant Therapy; Immune Checkpoint Inhibitor
• Intervention / Treatment: Drug: Pembrolizumab

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mengzhao Wang, MD.; Phone Number: +8613911235467; Email: mengzhaowang@sina.com
• Study Contact Backup: Name: Minjiang Chen, MD.; Phone Number: +8618618340880; Email: chenmj@pumch.cn

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chemotherapy plus 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	Drug: 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.; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MPR(major pathologic response)	more than 90 percent decrease in viable tumor	Up to 8weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete pathological (CPR) response rate	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)	8 weeks
EFS (event free survival)	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	8 weeks
OS (overall survival)	the time length from randomization (mainly from the receipt of pathology and genetic diagnosis reports)to death from any cause.	8 weeks
Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Evaluate adverse events of any cause, treatment-related adverse events, immune-mediated adverse events according to NCI-CTCAE V5.0	8 weeks
Evaluate tissue biomarkers	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.	8 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Mengzhao Wang, MD., Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): December 8, 2023
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 17, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: ZS-2847

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The result of the study and all the supporting informations will be shared in the form of publishing article.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No