A Randomized Phase II Trial of Adjuvant Pembrolizumab Versus Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153

Greg Durm, MD13 sites in 1 country244 target enrollmentMay 5, 2020

ConditionsNSCLC, Stage I

InterventionsPembrolizumab

DrugsPembrolizumab

Overview

Phase: Phase 2
Intervention: Pembrolizumab
Conditions: NSCLC, Stage I
Sponsor: Greg Durm, MD
Enrollment: 244
Locations: 13
Primary Endpoint: Disease Free Survival (DFS)
Status: Recruiting
Last Updated: 12 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Patients will be randomized (1:1) 4-12 weeks following surgery to either:

Arm A: Pembrolizumab 400 mg every 6 weeks × 9 cycles
Arm B: Observation

Stratification factors will include: PD-L1 TPS (<50% vs. ≥50%), and tumor size (1-2 cm vs. >2-4 cm)

Detailed Description

A randomized trial of adjuvant Pembrolizumab following surgical resection versus observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm. Patients will be randomized (1:1) 4-12 weeks following surgery to either: * Arm A: Pembrolizumab 400 mg every 6 weeks × 9 cycles * Arm B: Observation Stratification factors will include: PD-L1 TPS (\<50% vs. ≥50%), and tumor size (1-2 cm vs. \>2-4 cm) Primary Objective: * To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1 TPS score. Secondary Objectives: * To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves overall survival compared with observation in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size, regardless of PD-L1 TPS. * To evaluate the disease-free survival and overall survival rates at 1 year, 2 years, and 3 years on each arm. * To characterize the toxicity profile of adjuvant Pembrolizumab following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size. Exploratory Objectives: * To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size and a PD-L1 tumor proportion score (TPS) of ≥ 50%. * To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size and a high tumor mutation burden (TMB) defined as ≥ 10 mutations/MB. * To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size and a high tumor mutation burden (TMB) defined as ≥ 16 mutations/MB. * To evaluate the disease free survival and overall survival for patients stratified by PD-L1 status (TPS ≥ 50% vs. \< 50%), and tumor size (1-2 cm vs. \>2-4 cm). * To evaluate the association between various known prognostic variables, including, but not limited to, tumor differentiation (well-differentiated, moderately well differentiated, poorly differentiated), lymphovascular invasion, sex (male, female), PET max SUV and disease free survival and overall survival in patients treated with adjuvant Pembrolizumab for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size. * To evaluate whether the presence of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) following surgical resection predicts relapse in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size. * To evaluate whether the presence of ctDNA or CTCs following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm in size can predict which patients benefit from adjuvant Pembrolizumab compared to observation. * To evaluate potential biomarkers (which may include genomics, RNA, tumor infiltrating lymphocytes, CD4 and CD8 expression, JAK2, STK11/LB1 loss of function, macrophage profile, neutrophil/lymphocyte ratio, and microbiome) as prognostic or predictive for improved disease free survival and overall survival.

Registry

clinicaltrials.gov

Start Date

May 5, 2020

End Date

April 1, 2029

Last Updated

12 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Greg Durm, MD

Responsible Party

Sponsor Investigator

Principal Investigator

Greg Durm, MD

Principal Investigator

Big Ten Cancer Research Consortium

Eligibility Criteria

Inclusion Criteria

•The participant (or legally acceptable representative if applicable) must provide written informed consent for the study. The participant may also provide consent for future unspecified research samples. However, the participant may participate in the study without participating in the future unspecified research sample collection. NOTE: Initial informed consent will remain valid throughout the 12-week period between surgical resection and study registration unless, in the opinion of the treating investigator, the participant experiences a significant change in medical or mental status.
•Males and females age ≥ 18 years at the time of consent.
•ECOG Performance Status of 0-1 within 28 days prior to registration.
•Patients must have undergone complete surgical resection of their stage I NSCLC between 4-12 weeks prior to registration and have negative surgical margins (R0).
•NOTE: Both squamous and non-squamous histologies are allowed into the study. Cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus "non-squamous histology".
•NOTE: Staging will be according to the AJCC 8th edition.
•Pathological tumor size must be 1.0 - 4.0 cm in greatest dimension. NOTE: According to AJCC 8th edition, subjects with lepidic predominant adenocarcinoma should be staged based on their invasive tumor size and not their total tumor size (i.e., subjects with lepidic predominant tumors whose invasive tumor size is less than 1 cm are not eligible, even if their total tumor size is 1.0 cm or greater).
•Surgery for this lung cancer must be completed at least 28 days prior to registration.
•Must have either previous NGS and PD-L1 results available using the Dako 22C3 antibody or have archival tissue of surgical specimen from current diagnosis available to perform analyses. PD-L1 results via the Dako 22C3 antibody will be performed per standard of care from a CLIA-accredited laboratory and are required for stratification. If NGS results are not available, subjects must be able to provide at least 10 x 10µm unstained and 1 x 4µm H\&E slides from current diagnosis for future NGS and/or other genetic analyses.
•Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.

Exclusion Criteria

•Current lung cancer is \<1 cm or \> 4 cm in size or is stage II, III, or IV.
•Patients with tumors that are known to harbor actionable EGFR mutations.
•Prior chemotherapy, radiation therapy, or immunotherapy for the treatment of this lung cancer.
•Has a known active additional malignancy that is progressing or has required active treatment within the past 2 years. NOTE: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
•Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
•Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
•Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
•Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
•Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.
•Has had an allogenic tissue/solid organ transplant.

Arms & Interventions

Arm A- Pembrolizumab

Pembrolizumab 400mg IV every 6 weeks x 9 cycles

Intervention: Pembrolizumab

Outcomes

Primary Outcomes

Disease Free Survival (DFS)

Time Frame: Up to 3 years from time of randomization

To evaluate whether the addition of adjuvant Pembrolizumab following surgical resection improves disease free survival compared with observation following surgical resection in patients with stage I non-small cell lung cancer (NSCLC) that is between 1-4 cm in size, regardless of PD-L1 TPS score. Median Disease Free Survival (DFS) will be reported.