Pembrolizumab as Neoadjuvant Therapy for Resectable Stage IA3 to IIA Non-Small Cell Lung Cancer (NSCLC)

NCT04638582 | Terminated Phase 2

• 1 other identifier: MK3475-A74
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, single-site, open-label Phase II trial of neoadjuvant pembrolizumab (3 cycles) followed by surgery, versus concomitant neoadjuvant pembrolizumab with platinum doublet chemotherapy (3 cycles) followed by surgery for participants with Stage IA3, IB and IIA non-small-cell lung cancer (NSCLC). Participants will be offered pembrolizumab (6 cycles), and standard of care adjuvant chemotherapy (4 cycles) if applicable.

Conditions

Lung Cancer, Nonsmall Cell

Keywords

Non-Small Cell Lung Cancer; Immunotherapy; Immune Checkpoint Inhibition; Early Stage Lung Cancer; Neoadjuvant Therapy

Outcome Measures

Primary Outcomes (1)

• ctDNA resolution

  ctDNA resolution is defined as the change or resolution in tumor-derived DNA found in the bloodstream from diagnosis to after neoadjuvant therapy and after surgery, correlated with pathological complete response (pCR).

  Up to 2 years

Secondary Outcomes (5)

• Imaging measures of response

  Up to 3 years

• Pathological complete response (pCR) rate

  Up to 3 years

• Major pathological response (MPR) rate

  Up to 3 years

• Adverse event (AE) rate

  Up to 3 years

• Perioperative complications rate

  Up to 3 years

Other Outcomes (5)

• Overall survival (OS)

  Up to 3 years

• Disease-free survival (DFS)

  Up to 3 years

• Anatomical segmentectomy rate

  Up to 3 years

Study Arms (2)

Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy

EXPERIMENTAL

Neoadjuvant: Participants receive pembrolizumab \[200 mg, intravenous (IV)\] every 3 weeks for 3 cycles. Adjuvant: Participants receive pembrolizumab \[400 mg IV\] every 6 weeks for 6 cycles, and may receive histology-specific adjuvant chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 4 cycles, if indicated.

Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed

Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy

EXPERIMENTAL

Neoadjuvant: Participants receive pembrolizumab \[200 mg, intravenous (IV)\] every 3 weeks for 3 cycles in combination with standard of care histology-specific chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 3 cycles. Adjuvant: Participants receive pembrolizumab \[400 mg IV\] every 6 weeks for 6 cycles, and may receive histology-specific adjuvant chemotherapy \[consisting of carboplatin AUC 6 and paclitaxel 200 mg/m2, or carboplatin AUC 5 and paclitaxel 500 mg/m2\] every 3 weeks for 4 cycles, if indicated.

Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed

Interventions

Pembrolizumab DRUG

Neoadjuvant pembrolizumab 200 mg IV every 3 weeks, given on cycle day 1. Adjuvant pembrolizumab 400 mg IV every 6 weeks, given on cycle day 1.

Also known as: Keytruda, MK-3475

Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy; Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy

Carboplatin DRUG

Carboplatin AUC 6 IV (maximum dose: 900 mg) for squamous cell carcinoma, and AUC 5 IV (maximum dose: 750 mg) for non-squamous cell carcinoma, every 3 weeks, given on cycle day 1.

Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy; Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy

Paclitaxel DRUG

Paclitaxel 200 mg/m2 IV every 3 weeks, given on cycle day 1. Only given to participants with squamous cell carcinoma.

Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy; Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy

Pemetrexed DRUG

Pemetrexed 500 mg/m2 every 3 weeks, given on cycle day 1. Only given to participants with non-squamous cell carcinoma.

Neoadjuvant pembrolizumab + adjuvant pembrolizumab +/- adjuvant chemotherapy; Neoadjuvant pembrolizumab and chemotherapy + adjuvant pembrolizumab +/- adjuvant chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated, histologically confirmed (by core biopsy) NSCLC and histologically confirmed stages IA3, IB and IIA NSCLC (AJCC 8th edition).
• Able to undergo protocol therapy, including necessary surgery.
• If female: may participate if no active pregnancy, not breastfeeding, and at least one of the following: is not a woman of childbearing potential (WOCBP), or is a WOCBP using contraceptive methods.
• If male: must agree to refrain from donating sperm, and must either be abstinent or agree to use contraception.
• ECOG 0-1
• Available formalin-fixed paraffin embedded (FFPE) tumor tissue samples

You may not qualify if:

• Has one of the following tumor locations/types: NSCLC involving the superior sulcus, large cell neuroendocrine cancer (LCNEC) or sarcomatoid tumor.
• History of immunodeficiency, HBV, HCV, HIV. No HBV, HCV or HIV testing is required unless mandated by local health authority.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has had an allogenic tissue/solid organ transplant.
• Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients. (Refer to the respective Investigator's Brochure for a list of excipients.)
• Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents and/or to any of their excipients.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
• Has received colony-stimulating factors (eg, G-CSF, GM-CSF or recombinant erythropoietin) within 2 weeks before randomization
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received prior systemic anticancer therapy including investigational agents for the current malignancy prior to randomization/allocation.
• Has received prior radiotherapy within 2 weeks of start of trial treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has received a live or live attenuated vaccine within 30 days prior to the first dose of trial drug. Note: killed vaccines are allowed.

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (1)

McGill University Health Center

Montreal, Quebec, H4A3J1, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Carboplatin; Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Jonathan Spicer, MD, PhD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery, Principal Investigator

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: November 20, 2020
• Study Start: August 28, 2022
• Primary Completion: April 14, 2026
• Study Completion: April 14, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)