Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer [NEOMUN]
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Sponsor
- AIO-Studien-gGmbH
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Patients Treated in Compliance With Protocol
- Status
- Completed
- Last Updated
- last year
Overview
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.
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Cooperation and willingness to complete all aspects of the study
- •Signed and dated written informed consent must be given prior to study inclusion
- •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.
Exclusion Criteria
- •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.
- •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)
Arms & Interventions
Pembrolizumab
Pembrolizumab at fixed dose: 200 mg q3w i.v. for 2 cycles
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Patients Treated in Compliance With Protocol
Time Frame: From screening until surgery, ca. 6-8 weeks
The definition for this endpoint was neoadjuvant pembrolizumab treatment followed by successful curative intent tumor resection.
Tumor Response According to RECIST 1.1 Criteria
Time Frame: From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
Radiologic tumor assessments were performed at screening and pre-surgery.
Tumor Response Evaluation - Pathologic Response
Time Frame: From screening until surgery, ca. 6-8 weeks
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.
Tumor Response Evaluation - Δ Tumor Size
Time Frame: From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
Δ tumor size was defined as the difference \[mm\] between longest diameter at baseline and pre-surgery.
Tumor Response - Δ PET Activity
Time Frame: From screening until pre-surgery radiologic assessment, ca. 6-8 weeks
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.
Secondary Outcomes
- Disease-free Survival at 12 Months(12 months after surgery, i.e. circa 14 months after treatment start)
- Overall Survival at 24 Months(24 months after surgery, i.e. circa 26 months after treatment start)
- Overall Survival at 12 Months(12 months after surgery, i.e. circa 14 months after treatment start)
- Disease-free Survival at 6 Months(6 months after surgery, i.e. circa 8 months after treatment start)
- Overall Survival at 18 Months(18 months after surgery, i.e. circa 20 months after treatment start)