NCT02987998

Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in NSCLC

A Phase I Safety and Feasibility Study of Neoadjuvant Chemoradiation Plus Pembrolizumab Followed By Consolidation Pembrolizumab in Resectable Stage 3A Non-Small Cell Lung Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Nathan Pennell, MD, PhD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment. Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.

Detailed description

The primary hypothesis is that the addition of pembrolizumab to neoadjuvant concurrent chemoradiation, followed by consolidation pembrolizumab, will be safe and feasible to deliver to patients with resectable stage 3A Non-small cell lung cancer (NSCLC). This study also plans to observe the efficacy of this combination in the overall and biomarker-positive population. Primary Objective Primary objective of this phase 1 study is to determine safety and feasibility of MK3475 with standard of care therapy of chemotherapy with radiation for newly diagnosed stage 3 lung carcinoma. • To define the Safety, tolerability and feasibility of MK3475 in combination with chemotherapy with cisplatin and etoposide along with 45 Gy of radiation in newly diagnosed stage 3 non-small cell lung carcinoma. Secondary Objective(s) * Progression Free Survival * Objective response rate, * Complete pathologic response rate, * Nodal downstaging at surgery, * Overall survival, * Safety and tolerability Correlative Objective(s) Exploratory objectives: Overall response rate, progression free survival, overall survival in Programmed death-ligand (PDL-1) positive versus negative subgroups Study Design This is an open-label, single arm phase I trial of neoadjuvant chemotherapy + pembrolizumab with concurrent radiation followed by surgical resection and consolidation pembrolizumab in resectable stage 3A (N2+) NSCLC. Eligible patients will have biopsy-confirmed T1-3N2M0 (stage IIIA) non-small cell lung cancer (adenocarcinoma, squamous cell carcinoma, or large cell/NSCLC not otherwise specified), performance status 0-1, adequate lung function and deemed medically resectable by a thoracic surgeon, adequate organ function for chemotherapy, and no contraindications to pembrolizumab (i.e. autoimmune disorders or underlying pulmonary fibrosis). Because pembrolizumab has been safely added to multiple platinum doublet chemotherapy regimens in lung cancer but not yet tested in the setting of concurrent radiation, we plan to evaluate safety and feasibility of the combination therapy. 10 patients will be enrolled at the full starting dose of all 3 agents. If 3 or more (\>30%) have grade 3 or higher pulmonary toxicity or any grade 4 nonhematologic toxicity, the study will be stopped. If 2 or fewer have \> grade 3 pulmonary toxicity or \> grade 4 other nonhematologic toxicity, then an additional 10 will be enrolled. If 5 or fewer (\<25%) of the 20 patients have \> grade 3 pulmonary toxicity or \> grade 4 other nonhematologic toxicity, then this regimen will be deemed safe and feasible for further study.

Conditions

• Stage IIIA Non-Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Cisplatin	Cisplatin (50mg/m2 IV D1, 8, 29, 36)
DRUG	Etoposide	Etoposide (50mg/m2 IV D1-5, 29-33)
DRUG	Pembrolizumab	Pembrolizumab (200mg IV D1, 21, 42)
DRUG	Radiation	Radiation (1.8Gy/D to 45Gy in 25 fractions)

Timeline

• Start date: 2017-05-19
• Primary completion: 2022-11-28
• Completion: 2022-11-28
• First posted: 2016-12-09
• Last updated: 2022-12-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study