Neoadjuvant Pembrolizumab

NCT02818920 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00071629
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

Brief Summary

This multi-institutional, phase 2 clinical trial is studying two doses of pembrolizumab administered prior to surgery (neoadjuvant therapy) and 4 doses administered after surgery (adjuvant therapy) for stage IB, II or IIIA non-small cell lung cancer. Pembrolizumab is a type of immunotherapy that may enhance the ability of the immune system to fight off cancer. The study will investigate the effects of pembrolizumab on the immune system and how certain immune cells, called TILs (tumor infiltrating lymphocytes), respond to pembrolizumab. Previous studies suggest that pembrolizumab could alter the immune cells in a way that the the immune cells identify cancer cells. Pembrolizumab has been approved for the treatment of advanced lung cancer, but is investigational in this setting.

Conditions

Non-small Cell Lung Carcinoma

Keywords

Pembrolizumab; Neoadjuvant; Tumor Infiltrating Lymphocytes (TILs)

Outcome Measures

Primary Outcomes (1)

• Surgical Feasibility Rate as Measured by the Number of Subjects Who Undergo Surgery Following Neoadjuvant Pembrozulimab

  A patient who meets the eligibility criteria, has received at least 1 dose of pembrolizumab, and undergone surgery in the window of 29-56 days after initiation of pembrolizumab is considered surgically feasible. All other situations are considered infeasible.

  29-56 days after initiation of pembrolizumab

Other Outcomes (14)

• Objective Response Rate

  At the end of 2 cycles of neoadjuvant pembrolizumab (29-55 days after initiation)

• Disease-free Survival (DFS)

  Until disease recurrence or death (up to 5 years)

• Change in Blood-based Biomarker Values

  Baseline (day 0), before surgery (days 29-56), 3-6 weeks after surgery, and after completion of adjuvant pembrolizumab (estimated at 10.5 months from start depending on treatment components received by patient)

Study Arms (1)

Pembrolizumab prior to and after surgery

EXPERIMENTAL

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab (prior to surgery) 200 mg IV over 30 min, days 1 \& 22, two cycles; followed by surgery; followed by standard adjuvant chemotherapy (per med. oncologist) +/- radiation therapy per institutional standard of care; followed by adjuvant pembrolizumab 200 mg IV over 30 min every 21 days for 4 cycles -Note: Standard radiation therapy in selected patients for standard clinical indications

Also known as: Keytruda

Pembrolizumab prior to and after surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed NSCLC.
• Clinical stage IB (\>/= 3 cm per CT), Stage IIA/IIB, or Stage IIIA (N0-2) amenable to surgical resection.
• Primary tumor \>/= 3 cm (for all stages entered) to make it likely that excess tumor will be available after resection.
• Patient must be deemed a surgical candidate.
• ECOG performance status of 0 or 1 (Appendix C).
• No prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer.
• Adequate Organ Function
• Age ≥18 years.
• Non-pregnant. Females of child-bearing potential (not surgically sterilized or postmenopausal \[a woman who is \> 45 years of age and has not had menses for greater than 1 year\]) must test negative for pregnancy within 48 hours prior to any initial study procedure based on a serum pregnancy test.
• No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
• Signed written informed consent including HIPAA according to institutional guidelines.
• Patients must agree to research blood sampling to participate in study.
• Have measurable disease based on RECIST 1.1.
• Post-op predicted FEV1 and DLCO \> 40% predicted (or per institutional standard).

You may not qualify if:

• Treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry or used an investigational device within 4 weeks of the first dose of treatment.
• Has a known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to pembrolizumab or any of its excipients.
• Concurrent administration of any other anti-tumor therapy.
• Has received prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent.
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Inability to comply with protocol or study procedures.
• Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency etc) is not considered a form of systemic treatment. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[eg, Wegener's Granulomatosis\]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis).
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known additional invasive malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has had major surgery (other than definitive lung cancer surgery) within two weeks of study or other serious concomitant disorders that in the opinion of the investigator would compromise the safety of the patient or compromise the patient's ability to complete the study.

Sponsors & Collaborators

• Neal Ready MD PhD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Tong BC, Gu L, Wang X, Wigle DA, Phillips JD, Harpole DH Jr, Klapper JA, Sporn T, Ready NE, D'Amico TA. Perioperative outcomes of pulmonary resection after neoadjuvant pembrolizumab in patients with non-small cell lung cancer. J Thorac Cardiovasc Surg. 2022 Feb;163(2):427-436. doi: 10.1016/j.jtcvs.2021.02.099. Epub 2021 Apr 9.

  PMID: 33985811 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Neal Ready, MD, PhD
• Organization: Duke University

neal.ready@duke.edu

919-681-6932

Study Officials

• Neal Ready, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 28, 2016
• First Posted: June 30, 2016
• Study Start: January 1, 2017
• Primary Completion: March 19, 2019
• Study Completion: June 20, 2024
• Last Updated: March 17, 2026
• Results First Posted: February 18, 2020

Record last verified: 2025-07

Locations

US (3)