Adjuvant Pembrolizumab vs Observation Following Curative Resection for Stage I Non-small Cell Lung Cancer (NSCLC) With Primary Tumors Between 1-4 cm

NSCLC, Stage I Clinical Trial

Official title: 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

Status Recruiting

Clinical Trial Summary

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)

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC, Stage I

• NCT number: NCT04317534
• Study type: Interventional
• Source: Big Ten Cancer Research Consortium
• Contact: Greg Durm, MD
• Phone: 317-944-3940
• Email: gdurm@iu.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: May 5, 2020
• Completion date: April 2026