Phase II Trial of Continuation Therapy in Advanced NSCLC

NCT ID: NCT03083808

Last Updated: 2023-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2022-03-03

Brief Summary

This is a single-arm phase II study of continuation immunotherapy with pembrolizumab following initial benefit (CR, PR, or SD ≥ 3 months) with a PD-1 or PD-L1 inhibitor.

Detailed Description

OUTLINE: This is a multi-center study.

Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m2 IV D1 and D8 every three weeks, docetaxel 75mg/m2 IV D1 every three weeks, or pemetrexed 500mg/m2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity.

Administration Sequence: First Sequence

• Pembrolizumab 200mg IV on Day 1 (cycle = 21 days)

Administration Sequence: Second Sequence

• Gemcitabine 1000mg/m^2 IV on Days 1,8 (cycle = 21 days)
• Docetaxel 75mg/^2 IV on Days 1,8 (cycle = 21 days)
• Pemetrexed 500mg/m^2 IV on Day 1 (cycle -= 21 days)

Conditions

Non-Small-Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab 200mg IV every 21 days

Patients who have been treated with a PD-1 or PD-L1 inhibitor and experienced a PFS of ≥3 months will be enrolled within 6 weeks of last dose of PD-1 or PD-L1 inhibitor. On Day 1 of each 3-week cycle, subjects will first receive pembrolizumab at a dose of 200mg IV every three weeks in combination with chemotherapy. Partner chemotherapy will be either gemcitabine 1000mg/m\^2 IV D1 and D8 every three weeks, docetaxel 75mg/m\^2 IV D1 every three weeks, or pemetrexed 500mg/m\^2 IV D1 every 3 weeks (pemetrexed for non-squamous histologies only). Subjects will continue to receive this combination until progression or intolerable toxicity.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab 200mg IV every 21 days

+

Physician's choice chemotherapy with one of the following every 21 days:

• Docetaxel 75mg/m2 IV
• Pemetrexed 500mg/m2 IV (non-squamous only)
• Gemcitabine 1000mg/m2 IV on days 1 and 8

Interventions

Pembrolizumab

Pembrolizumab 200mg IV every 21 days

+

Physician's choice chemotherapy with one of the following every 21 days:

• Docetaxel 75mg/m2 IV
• Pemetrexed 500mg/m2 IV (non-squamous only)
• Gemcitabine 1000mg/m2 IV on days 1 and 8

Intervention Type: DRUG

Other Intervention Names

Keytruda®; MK-3475

Eligibility Criteria

Inclusion Criteria

• Written informed consent and HIPAA authorization for release of protected health information.
• Age ≥ 18 years at the time of consent.
• Histological or cytological evidence of stage IV NSCLC (any histology)
• Subjects must have progressed on or after previous platinum-based chemotherapy. Chemotherapy may have previously been given with a PD-1 or PD-L1 inhibitor. Subjects must have also progressed on or after receiving any PD-1 or PD-L1 inhibitor (including pembrolizumab) as their most recent therapy and must have had at least a 3-month PFS on this therapy.
• Subjects must be enrolled on the trial within 6 weeks of their last infusion of PD-1 or PD-L1 inhibitor therapy.
• Subjects whose tumors harbor a mutation in EGFR exon 19 or 21 or have gene rearrangements in ALK or ROS1 must have already been treated with standard targeted therapies. NOTE: Subjects must also have progressed on or after platinum-containing combination chemotherapy.
• ECOG Performance Status of 0 or 1 within 28 days prior to registration for protocol therapy.
• Must be fit enough to receive next-line chemotherapy (either gemcitabine, docetaxel, or pemetrexed [non-squamous only]) according to the discretion of the treating physician.
• Adequate laboratory values obtained within 28 days prior to registration for protocol therapy.
• Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test within 7 days prior to study registration and/or within 72 hours of first dose of study drugs. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Women of childbearing potential must be willing to use two methods of contraception or abstain from heterosexual activity from the point of registration through 120 days after the last dose of study drug.
• Male subjects capable of fathering a child must agree to use an adequate method of contraception starting with the first dose of the study drug through 120 days after the last dose of the study drug.

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

• 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.
• Active central nervous system (CNS) metastases. NOTE: Subjects who are symptomatic or have not undergone prior brain imaging must undergo a head computed tomography (CT) scan or brain MRI within 28 days prior to registration to exclude brain metastases.
• Treatment with any investigational agent within 28 days prior to registration for protocol therapy with the exception of PD-1 or PD-L1 inhibitors.
• No active second cancers with the exception of localized non-melanoma skin cancer, in-situ cervical or in-situ bladder cancer.
• Evidence of active autoimmune disease requiring systemic treatment within the past 90 days or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
• History of (non-infectious) pneumonitis requiring treatment with corticosteroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• History of an immune-related toxicity requiring treatment with corticosteroids during prior PD-1/ PD-L1 inhibitor treatment.
• Diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy or other immunosuppressive therapy (excludes inhaled corticosteroids) within 7 days of study registration.
• History of psychiatric illness or social situations that would limit compliance with study requirements.
• Clinically active infection (≥ Grade 2) as judged by the site investigator.
• Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C. NOTE: HIV, HBV or HCV testing is not required.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the site investigator.
• Known history of active TB (Bacillus Tuberculosis).
• History of hypersensitivity to pembrolizumab, docetaxel, gemcitabine, pemetrexed or any of their excipients.
• Has received a live vaccine within 30 days prior to planned start of study therapy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Big Ten Cancer Research Consortium

OTHER

Sponsor Role: collaborator

Greg Durm, MD

OTHER

Sponsor Role: lead

Responsible Party

Greg Durm, MD

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Greg Durm, M.D.

Role: STUDY_CHAIR

Big Ten Cancer Research Consortium

Locations

University of Illinois Cancer Center

Chicago, Illinois, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

University of Iowa Hospital Clinics

Iowa City, Iowa, United States

University of Minnesota Medcical Center

Minneapolis, Minnesota, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.bigtencrc.org

Big Ten Cancer Research Consortium Website

Other Identifiers

BTCRC-LUN15-029

Identifier Type: -

Identifier Source: org_study_id