Re-challenge Pembrolizumab Study as a Second or Further Line in Patients With Advanced NSCLC

NCT03526887 | Completed Phase 2 Results

• 2 other identifiers: GECP 17/02_REPLAY2017-003947-39
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 19

Brief Summary

Exploratory phase II trial of intravenous (IV) Pembrolizumab MK-3475 as second or further line with advanced Non-small cell Lung Cancer (NSCLC) who have failed to a prior treatment with anti-PDL1 drug. Pembrolizumab 200 mg ,Q3W, IV infusion, Day 1 of each 3 week cycle will be administered until disease progression.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy of Pembrolizumab Re-challenge Measured by Overall Survival

  Overall survival: Defined as the length of time from either the date of diagnosis or the start of the treatment that patients diagnosed with the disease are still alive.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months.

Secondary Outcomes (2)

• Efficacy of Pembrolizumab Re-challenge Measured by Progression Free Survival (PFS) Per RECIST v1.1.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.

• Best Global Response

  From the date of randomization until end of follow up, up to 36 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

Patients who experienced progression disease while on treatment progression disease \< 12 weeks after stopping treatment. After that the patients took chemotherapy ≥ 4 cycles and progressed again. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg

Drug: Pembrolizumab

Cohort 2

EXPERIMENTAL

Stop treatment and progression \> 12 weeks after stopping treatment. After the last progression the patient is included in the study to be retreated with Pembrolizumab 200mg

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

200 mg, Q3W

Also known as: KEYTRUDA

Cohort 1

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cythological confirmed NSCLC advanced or locally advanced disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) not amenable to radical treatment (IIIA, IIIB, IIIC, IV), squamous or non-squamous, recurrent after at least one prior line.
• The subject must be willing and able to provide written informed consent/assent for the trial.
• Patient must be aged ≥ 18 years of age on day of signing informed consent.
• Documented prior benefit (Stable Disease, Partial Response, Complete Response) to check point PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab, Avelumab or others) for at least 16 weeks (Stable Disease, Partial Response, Complete Response) and progression while on treatment (or \<12 weeks after stopping) with the same PD-1/PD-L1 inhibitors. These patients should have received subsequent treatment with Chemotherapy for at least 4 courses (Cohort 1) OR Documented prior benefit (Stable Disease, Partial Response, Complete Response) to check point PD1/PDL1 inhibitor (Nivolumab, Pembrolizumab, Durvalumab, Atezolizumab, Avelumab or others) for at least 16 weeks (Stable Disease, Partial Response, Complete Response) and progression \>12 weeks after stopping treatment (Cohort 2). No subsequent treatment before rechallenge is allowed in this cohort
• Patient must be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. PDL1 must be evaluable and at least 1% positive in tumor tissue. 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. Note: If a new sample core or excisional biopsy cannot be obtained but the patient can be included in the study and start the treatment and the archival tumor tissue could be sent afterwards for the central laboratory confirmation. If no previous PDL1 result is available from the archival tissue, the patient cannot be included in the trial until central laboratory PDL1 result is available. Other cases could be consulted with the trail chair.
• Have a performance status of 0-1 on the ECOG Performance Scale.
• Demonstrate adequate organ function, all screening labs should be performed within 7 days of treatment initiation.
• 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 must be willing to use an adequate method of 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 must agree to use an adequate method of 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.
• All patients will be required to submit a tumor sample for PD-L1 IHC expression. If the sample is inadequate for analysis, another sample could be provided. If a new sample cannot be obtained due to technical or clinical reasons, archival tissue can be sent. Other cases could be consulted with the trial chair.

You may not qualify if:

• 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.
• 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 at a dose over 10 mg of prednisone or equivalent, 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 a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Documented EGFR sensitizing mutation.
• Documented ALK translocation.

Sponsors & Collaborators

• Spanish Lung Cancer Group: lead

Study Sites (19)

Hospital General Universitario de Elche

Elche, Alicante, 03203, Spain

Location

H. Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Consorci Sanitari de Terrassa

Terrassa, Barcelona, 08227, Spain

Location

Complejo Hospitalario de la Coruña

A Coruña, Coruña, 15006, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital de Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital de Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

H.U.Vall D´Hebrón

Barcelona, 08035, Spain

Location

Hospital Dr. Josep Trueta

Girona, 17007, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Complejo Asistencial Universitario de León

León, 24071, Spain

Location

Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

H. 12 de Octubre

Madrid, 28041, Spain

Location

Puerta de Hierro

Madrid, Spain

Location

H. Son Llàtzer

Palma de Mallorca, 07198, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Hospital La Fe

Valencia, 46026, Spain

Location

Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Related Links

• Web page of the sponsor where users can find more information about Fundación GECP studies

MeSH Terms

Conditions

Lung Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Eva Pereira
• Organization: Fundación GECP

gecp@gecp.org

+34934302006

Study Officials

• Luís Paz Ares, MD

  Hospital 12 de Octubre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 groups depending on when the progression disease is diagnosed but the treatment after progression will be the same: Pembrolizumab

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 16, 2018
• Study Start: July 15, 2018
• Primary Completion: December 30, 2022
• Study Completion: March 9, 2023
• Last Updated: March 24, 2025
• Results First Posted: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (19)