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CompletedNCT03197467NEOMUNUpdated Apr 4, 2025Results posted

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

A Phase 2 interventional study of Pembrolizumab in Non-small Cell Lung Cancer (NSCLC), sponsored by AIO-Studien-gGmbH. Completed at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-04.

Sponsored by AIO-Studien-gGmbH · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

The study is designed as an open-label, single arm, prospective, monocenter, phase II study of pembrolizumab in a neoadjuvant setting in patients with resectable NSCLC stage II/IIIA suitable for curative intent surgery, taking place in Germany. Planned sample size is N=30.

Investigational drug is Pembrolizumab at fixed dose, given 200 mg q3w i.v. for 2 cycles. After completion of immunotherapy lobectomy/ bilobectomy with curative intent is scheduled.

Primary objectives are to assess feasibility and safety of a neoadjuvant application of pembrolizumab and to assess antitumor activity of pembrolizumab with regard to clinical and pathologic tumor response. Secondary objective is to assess the impact of neoadjuvant pembrolizumab on patient disease free and overall survival. Exploratory objective is o explore potential predictive biomarkers for pembrolizumab efficacy (immune cell imaging).

02

Conditions studied

  • Non-small Cell Lung Cancer (NSCLC)
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,558 are open to participants now.

This study's enrollment of 30 is below the median of 60 across 5,296 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

AIO-Studien-gGmbH is the lead sponsor of 61 studies on the registry; 5 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Cooperation and willingness to complete all aspects of the study
  2. Signed and dated written informed consent must be given prior to study inclusion
  3. Histological or cytological confirmed NSCLC

  4. Clinical stage II-IIIA according to the TNM classification, 7th edition:

    stage IIIa: T1/T2 N2 (IIIa1-3 Robinson classification)

  5. Adequate disease staging by PET/CT and brain MRI
  6. At least 1 measurable lesion according to RECIST 1.1
  7. Age ≥ 18 years
  8. ECOG performance status 0 - 1
  9. 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.
  10. 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

  11. Adequate bone marrow function, liver and renal function:

    1. Absolute neutrophil count ≥ 1.5 x 109/L
    2. Thrombocytes ≥ 100 x 109/L
    3. Hemoglobin ≥ 9 g/dL without transfusion or EPO dependency (within 7 days of assessment)
    4. INR \< 1.4 ULN and PTT \< 40 seconds during the last 7 days before therapy
    5. Bilirubin \< 1.5 x upper limit of normal
    6. AST (GOT) and ALT (GPT) \< 2.5 x ULN
    7. Albumin >2.5 mg/dL
    8. Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
  12. Adequate lung and cardiac function for intended lung resection according to German S3 guideline

Exclusion criteria

Exclusion Criteria:

  1. Anticancer treatment during the last 30 days prior to start of treatment, including systemic therapy, radiotherapy or major surgery
  2. Participation in a clinical trial within the last 30 days prior to study treatment
  3. History of allogeneic tissue/solid organ transplant
  4. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  5. Evidence of interstitial lung disease.
  6. cT4 tumor
  7. Symptomatic acute cardiovascular or cerebrovascular disease
  8. Known active HBV, HCV or HIV infection
  9. Has any other active infection requiring systemic therapy.
  10. Patients with active tuberculosis
  11. 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)
  12. 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.
  13. Patient has had a prior monoclonal antibody within 4 weeks prior to study Day 1
  14. Patient has had prior chemotherapy, targeted small molecule therapy, or radiation therapy in history.
  15. 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.
  16. Has received a live vaccine within 30 days prior to the first dose of trial treatment. [Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.]
  17. Has known hypersensitivity to pembrolizumab or any of the constituents of the product.
  18. Other active malignancy requiring treatment Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  19. Lactating or pregnant women, women of child-bearing potential who do not agree to the usage of highly effective contraception methods (allowed methods of contraception, meaning methods with a rate of failure of less than 1% per year are implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner). Women of childbearing potential must have a negative pregnancy test (serum β-hCG) at Screening.
  20. Any psychiatric illness that would affect the patient's ability to understand the demands of the clinical trial
  21. Patient has already been recruited in this trial
  22. Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  23. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Pembrolizumab

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

    Drug: Pembrolizumab

Interventions

  • DrugPembrolizumab

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

06

What researchers measure

Primary outcomes

  1. Number of Patients Treated in Compliance With Protocol

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

    Time frame: From screening until surgery, ca. 6-8 weeks

  2. Tumor Response According to RECIST 1.1 Criteria

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

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

  3. 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.

    Time frame: From screening until surgery, ca. 6-8 weeks

  4. Tumor Response Evaluation - Δ Tumor Size

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

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

  5. 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.

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

Secondary outcomes

  1. Disease-free Survival at 6 Months

    Probability of disease-free survival (DFS) was calculated using Kaplan-Meier statistics from date of surgery to the date until tumor recurrence or death. Follow-up was until 24 months after last-patient-out.

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

  2. Disease-free Survival at 12 Months

    Probability of disease-free survival (DFS) was calculated from date of surgery until tumor recurrence or death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

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

  3. Overall Survival at 12 Months

    Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

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

  4. Overall Survival at 18 Months

    Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

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

  5. Overall Survival at 24 Months

    Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

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

07

Results

Posted Apr 4, 2025

Participant flow

Participant flow — Overall Study
MilestonePembrolizumab
Started30
Completed29
Not completed1
Withdrew: Withdrawal by subject1

Outcome measures

PrimaryNumber of Patients Treated in Compliance With Protocol

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

Time frame:
From screening until surgery, ca. 6-8 weeks
Reported as:
Count of participants · Participants
Number of Patients Treated in Compliance With Protocol
ParticipantsPembrolizumab
Number of Patients Treated in Compliance With Protocol29
PrimaryTumor Response According to RECIST 1.1 Criteria

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

Time frame:
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
Reported as:
Count of participants · Participants
Tumor Response According to RECIST 1.1 Criteria
ParticipantsPembrolizumab
Complete response0
Partial response6
Stable disease19
Progressive disease3
PrimaryTumor 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.

Time frame:
From screening until surgery, ca. 6-8 weeks
Reported as:
Count of participants · Participants
Tumor Response Evaluation - Pathologic Response
ParticipantsPembrolizumab
Grade I4
Grade IIa18
Grade IIb3
Grade III4
PrimaryTumor Response Evaluation - Δ Tumor Size

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

Time frame:
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
Reported as:
Median · mm
Tumor Response Evaluation - Δ Tumor Size
mmPembrolizumab
Tumor Response Evaluation - Δ Tumor Size-4.0 (-13.5 to 0.0)
PrimaryTumor 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.

Time frame:
From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
Reported as:
Median · standardized uptake value [SUV]
Tumor Response - Δ PET Activity
standardized uptake value [SUV]Pembrolizumab
Tumor Response - Δ PET Activity-1 (-7 to 2)
SecondaryDisease-free Survival at 6 Months

Probability of disease-free survival (DFS) was calculated using Kaplan-Meier statistics from date of surgery to the date until tumor recurrence or death. Follow-up was until 24 months after last-patient-out.

Time frame:
6 months after surgery, i.e. circa 8 months after treatment start
Reported as:
Number · Probablity of DFS in %
Disease-free Survival at 6 Months
Probablity of DFS in %Pembrolizumab
Disease-free Survival at 6 Months86.2 (67.3 to 94.6)
SecondaryDisease-free Survival at 12 Months

Probability of disease-free survival (DFS) was calculated from date of surgery until tumor recurrence or death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

Time frame:
12 months after surgery, i.e. circa 14 months after treatment start
Reported as:
Number · Probablity of DFS in %
Disease-free Survival at 12 Months
Probablity of DFS in %Pembrolizumab
Disease-free Survival at 12 Months86.2 (67.3 to 94.6)
SecondaryOverall Survival at 12 Months

Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

Time frame:
12 months after surgery, i.e. circa 14 months after treatment start
Reported as:
Number · Probability of OS in %
Overall Survival at 12 Months
Probability of OS in %Pembrolizumab
Overall Survival at 12 Months93.1 (75.1 to 98.2)
SecondaryOverall Survival at 18 Months

Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

Time frame:
18 months after surgery, i.e. circa 20 months after treatment start
Reported as:
Number · Probability of OS in %
Overall Survival at 18 Months
Probability of OS in %Pembrolizumab
Overall Survival at 18 Months89.7 (71.3 to 96.5)
SecondaryOverall Survival at 24 Months

Probability of overall survival (OS) was calculated from date of surgery until date of death using Kaplan-Meier statistics. Follow-up was until 24 months after last-patient-out.

Time frame:
24 months after surgery, i.e. circa 26 months after treatment start
Reported as:
Number · Probability of OS in %
Overall Survival at 24 Months
Probability of OS in %Pembrolizumab
Overall Survival at 24 Months86.2 (67.3 to 94.6)

Adverse events

Collected over Adverse events were recorded from signing of informed consent until 90 days after last dose of IMP (total: 20-22 weeks) or for 6 weeks after surgery (total: 12-14 weeks) if the subject initiated new anticancer therapy. Deaths were recorded for up to 26 months after treatment initiation.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pembrolizumab5/29 (17.2%)8/29 (27.6%)21/29 (72.4%)
Most frequent serious events
Most frequent serious events
EventPembrolizumab
PneumoniaInfections and infestations2/29
HyperthyroidismEndocrine disorders1/29
ColitisGastrointestinal disorders1/29
GastritisGastrointestinal disorders1/29
Acute hepatic failureHepatobiliary disorders1/29
Herpes zosterInfections and infestations1/29
Lichen planusSkin and subcutaneous tissue disorders1/29
Gastric ulcerGastrointestinal disorders1/29
Most frequent other events
Showing 10 of 12
Most frequent other events
EventPembrolizumab
CoughRespiratory, thoracic and mediastinal disorders5/29
FatigueGeneral disorders4/29
DiarrhoeaGastrointestinal disorders3/29
NauseaGastrointestinal disorders3/29
PneumoniaInfections and infestations3/29
DizzinessNervous system disorders3/29
Autoimmune thyreoditisEndocrine disorders2/29
HyperthyroidismEndocrine disorders2/29
VomitingGastrointestinal disorders2/29
PainGeneral disorders2/29

Baseline characteristics

Age, Continuous
Age, Continuous(years)Pembrolizumab
Median60 (40 to 83)
Sex: Female, Male
Sex: Female, Male(Participants)Pembrolizumab
Female16
Male13
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Pembrolizumab
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White28
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Pembrolizumab
Germany29
ECOG status
ECOG status(Participants)Pembrolizumab
ECOG 014
ECOG 115
08

Study locations

1 site
  • Universitätsklinikum Heidelberg
    Heidelberg, 69126, Germany
09

References and documents

Publications

  • 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. PubMed 34761878 ↗
  • 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. PubMed 33529989 ↗
  • 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. PubMed 31046714 ↗

Study documents

  • Study protocol · Sep 22, 2020
  • Statistical analysis plan · Mar 9, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03197467
Lead sponsor
AIO-Studien-gGmbH
Collaborators
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Jun 23, 2017
Start date
Jun 18, 2018
Primary completion
Oct 30, 2021
Completion
May 5, 2023
Results posted
Apr 4, 2025
Last update
Apr 4, 2025

Study contacts

Martin E. Eichhorn, PD Dr. med.
principal investigator · University Hospital Heidelberg

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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