Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer

NCT03197467 | Completed Phase 2 Results

• 3 other identifiers: 0316-ASG2016-002170-13MISP 52887
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

NEOMUN is designed as an open-label, single arm, prospective, monocenter, phase II study of pembrolizumab in a neoadjuvant setting in patients with non-small cell lung cancer of Stage II/IIIA suitable for curative intent surgery.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Outcome Measures

Primary Outcomes (5)

• Number of Patients Treated in Compliance With Protocol

  The definition for this endpoint was neoadjuvant pembrolizumab treatment followed by successful curative intent tumor resection.

  From screening until surgery, ca. 6-8 weeks

• Tumor Response According to RECIST 1.1 Criteria

  Radiologic tumor assessments were performed at screening and pre-surgery.

  From screening until pre-surgery radiologic assessment, ca. 6-8 weeks

• Tumor Response Evaluation - Pathologic Response

  Pathologic regression grading according to Junker criteria. The following grades are defined: Grade I No tumor regression or only spontaneous tumor regression in the sections of the primary tumor and mediastinal lymph nodes. Grade IIa Morphological signs of therapy-induced tumor regression in the sections of the primary tumor and/or mediastinal lymph nodes: More than 10% vital tumor tissue Grade IIb Morphological signs of therapy-induced tumor regression: Less than 10% vital tumor tissue Grade III Complete tumor regression, no evidence of vital tumor in the sections of the primary tumor and/or mediastinal lymph nodes. Regression grades IIb and III suggest a good response to neoadjuvant therapy. Reference: Junker K, Langner K, Klinke F, Bosse U, Thomas M. Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. Chest 2001; 120:1584-91.

  From screening until surgery, ca. 6-8 weeks

• Tumor Response Evaluation - Δ Tumor Size

  Δ tumor size was defined as the difference \[mm\] between longest diameter at baseline and pre-surgery.

  From screening until pre-surgery radiologic assessment, ca. 6-8 weeks

• Tumor Response - Δ PET Activity

  Δ PET activity (standardized uptake value \[SUV\]). This method uses radiolabeled tracer 82-deoxy-2-\[18F\]fluoro-D-glucose, FDG) during PET imaging of the tumor and accumulation of radiolabeled FDG measured by the PET scanner. Accumulation of FDG relative to normal tissue is related to the proliferative activity of malignant tissue and to the number of viable tumor cells. The endpoint is based on per-patient changes in tumor maximal standardized uptake value during PET examinations of the tumor before the start of treatment and after 2 cycles of neoadjuvant immunotherapy, i.e. between screening and shortly before surgery. Reduction of proliferative activity or of the number of viable tumor cells results in negative values.

  From screening until pre-surgery radiologic assessment, ca. 6-8 weeks

Secondary Outcomes (5)

• Disease-free Survival at 6 Months

  6 months after surgery, i.e. circa 8 months after treatment start

• Disease-free Survival at 12 Months

  12 months after surgery, i.e. circa 14 months after treatment start

• Overall Survival at 12 Months

  12 months after surgery, i.e. circa 14 months after treatment start

• Overall Survival at 18 Months

  18 months after surgery, i.e. circa 20 months after treatment start

• Overall Survival at 24 Months

  24 months after surgery, i.e. circa 26 months after treatment start

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Pembrolizumab at fixed dose: 200 mg q3w i.v. for 2 cycles

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab at fixed dose: 200 mg q3w i.v. for 2 cycles

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cooperation and willingness to complete all aspects of the study
• Histological or cytological confirmed NSCLC
• Clinical stage II-IIIA according to the TNM classification, 7th edition:
• stage IIIa: T1/T2 N2 (IIIa1-3 Robinson classification)
• Adequate disease staging by PET/CT and brain MRI
• At least 1 measurable lesion according to RECIST 1.1
• Age ≥ 18 years
• ECOG performance status 0 - 1
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Male subjects of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Adequate bone marrow function, liver and renal function:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Thrombocytes ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
• INR \< 1.4 ULN and PTT \< 40 seconds during the last 7 days before therapy

You may not qualify if:

• Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
• Participation in a clinical trial within the last 30 days prior to study treatment
• History of allogeneic tissue/solid organ transplant
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Evidence of interstitial lung disease.
• cT4 tumor
• Symptomatic acute cardiovascular or cerebrovascular disease
• Known active HBV, HCV or HIV infection
• Has any other active infection requiring systemic therapy.
• Patients with active tuberculosis
• Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• A diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1
• Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy in history.
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Related Publications (3)

• Shi Y, Li J, Chen M, Liu H, Ma D, Lin Y, Wang M, Xu Y. Sarcoidosis-like reaction after neoadjuvant pembrolizumab combined with chemotherapy mimicking disease progression of NSCLC induced encouraging discovery of pathological complete response. Thorac Cancer. 2021 Dec;12(24):3433-3436. doi: 10.1111/1759-7714.14228. Epub 2021 Nov 11.

  PMID: 34761878 DERIVED

• Eichhorn F, Klotz LV, Kriegsmann M, Bischoff H, Schneider MA, Muley T, Kriegsmann K, Haberkorn U, Heussel CP, Savai R, Zoernig I, Jaeger D, Thomas M, Hoffmann H, Winter H, Eichhorn ME. Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Lung Cancer. 2021 Mar;153:150-157. doi: 10.1016/j.lungcan.2021.01.018. Epub 2021 Jan 21.

  PMID: 33529989 DERIVED

• Eichhorn F, Klotz LV, Bischoff H, Thomas M, Lasitschka F, Winter H, Hoffmann H, Eichhorn ME. Neoadjuvant anti-programmed Death-1 immunotherapy by Pembrolizumab in resectable nodal positive stage II/IIIa non-small-cell lung cancer (NSCLC): the NEOMUN trial. BMC Cancer. 2019 May 2;19(1):413. doi: 10.1186/s12885-019-5624-2.

  PMID: 31046714 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: AIO-Studien-gGmbH Help Desk
• Organization: AIO-Studien-gGmbH

info@aio-studien-ggmbh.de

0049-30-8145344

Study Officials

• Martin E. Eichhorn, PD Dr. med.

  University Hospital Heidelberg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 23, 2017
• Study Start: June 18, 2018
• Primary Completion: October 30, 2021
• Study Completion: May 5, 2023
• Last Updated: April 4, 2025
• Results First Posted: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)