Switch Maintenance Pembrolizumab in Patients With NSCLC After First Line Platinum Doublet Chemotherapy

NCT02705820 | Completed Phase 2 Results DMC

• 1 other identifier: 3475-449
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Single arm one stage Phase II study: post 4-6 cycles platinum doublet chemotherapy for patients with metastatic Non Small Cell Lung Cancer (NSCLC) offering Pembrolizumab as maintenance therapy to non-progressors with primary endpoint: Immune Related Progression Free Survival (irPFS) at 1 year. Aim to show that this is at least 25% (compared to an expected 12% 1 year PFS based on the Pemetrexed and Erlotinib maintenance trials).

Conditions

Metastatic Non Small Cell Lung Cancer

Keywords

Metastatic, Lung Cancer, Switch, Maintenance, Pembrolizumab.

Outcome Measures

Primary Outcomes (1)

• Immune Related Progression Free Survival (irPFS) at 1 Year

  To investigate whether treatment with pembrolizumab improves 1 year irPFS, compared to historical controls (from the Pemetrexed and Erlotinib maintenance trials). Aim to show that this is at least 25% (compared to an expected 12% 1 year PFS based on the Pemetrexed and Erlotinib maintenance trials) using a one stage phase II Fleming's design.

  4 years

Secondary Outcomes (6)

• Response Rates Using RECIST Version 1.1

  7 years

• Response Rates With Immune Related Response Criteria (irRC)

  7 years

• Radiological Progression Free Survival (PFS) Using RECIST Criteria Version 1.1

  7 years

• Immune-related PFS Using irRC

  7 years

• Overall Survival

  7 years

Study Arms (1)

single arm study

EXPERIMENTAL

experimental treatment with maintenance pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Switch maintenance pembrolizumab treatment

Also known as: MK-3475

single arm study

Eligibility Criteria

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

You may qualify if:

• In order to be eligible for participation in this trial, the subject must:
• Be willing and able to provide written informed consent/assent for the trial.
• Be above 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.
• Have a performance status of 0 to 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN, AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 g/L Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 - Contraception, for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Have completed more than six (6) cycles of first line platinum doublet chemotherapy or more than six (6) have elapsed from the last chemotherapy administration of the first line chemotherapy with platinum doublet.
• 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 history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional 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.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Bank of Cyprus Oncology Centre: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Bank of Cyprus Oncology Centre

Nicosia, Strovolos, 2006, Cyprus

Location

Related Publications (2)

• Kakouri AC, Spiliotaki M, Loizidou EM, Stylianou I, Papageorgiou E, Panayi CG, Constantinou AI, Charalambous H, Deltas C, Papagregoriou G. Monitoring pembrolizumab response in patients with metastatic non-small cell lung cancer using circulating tumour DNA and circulating tumour cells. Transl Lung Cancer Res. 2025 Jun 30;14(6):1945-1960. doi: 10.21037/tlcr-2024-1095. Epub 2025 Jun 26.

  PMID: 40673096 DERIVED

• Charalambous H, Brown C, Vogazianos P, Katsaounou K, Nikolaou E, Stylianou I, Papageorgiou E, Vraxnos D, Aristodimou A, Chi J, Costeas P, Shammas C, Apidianakis Y, Antoniades A. Dysbiosis in the Gut Microbiome of Pembrolizumab-Treated Non-Small Lung Cancer Patients Compared to Healthy Controls Characterized Through Opportunistic Sampling. Thorac Cancer. 2025 May;16(9):e70075. doi: 10.1111/1759-7714.70075.

  PMID: 40356191 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Harris Charalambous
• Organization: Bank Of Cyprus Oncology Centre

haris.charalambous@bococ.org.cy

+35722847300

Study Officials

• Dr Haris Charalambous, BM MRCP FRCR

  Consultant Oncologist, BOC Oncology Centre

  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: PRINCIPAL INVESTIGATOR
• PI Title: Dr Haris Charalambous BM MRCP FRCR

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: March 11, 2016
• Study Start: April 25, 2016
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: June 17, 2025
• Results First Posted: January 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CY (1)