Phase II Trial of Continuation Therapy in Advanced NSCLC

NCT03083808 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BTCRC-LUN15-029
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

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.

Conditions

Non-Small-Cell Lung Cancer

Keywords

PD-1; PD-L1 Inhibitor; Pembrolizumab; Docetaxel; Pemetrexed; Gemcitabine

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter(LD) of target lesions; Progressive Disease (PD): \>= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. PFS was defined as time from starting treatment to disease progression met by RECIST 1.1, start of additional anticancer therapy before progression, or death from any cause.

  Time of treatment start until the criteria for disease progression or death, up to a maximum of 28 months

Secondary Outcomes (5)

• Clinical Benefit Rate (CBR)

  Up to a maximum of 28 months

• Objective Response Rate (ORR)

  Up to a maximum of 28 months

• Overall Survival (OS)

  Time of treatment start until death or up to a maximum of 40 months

• Number of Participants With Adverse Events

  Adverse events were recorded from time of registration until 30 days after discontinuation of study drug(s) up to a maximum of 25 months.

• Progression Free Survival (PFS) by irRECIST

  Time of treatment start until the criteria for disease progression or death, up to a maximum of 28 months

Study Arms (1)

Pembrolizumab 200mg IV every 21 days

EXPERIMENTAL

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.

Drug: Pembrolizumab

Interventions

Pembrolizumab 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

Also known as: Keytruda®, MK-3475

Pembrolizumab 200mg IV every 21 days

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Greg Durm, MD: lead
• Merck Sharp & Dohme LLC: collaborator
• Big Ten Cancer Research Consortium: collaborator

Study Sites (5)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospital Clinics

Iowa City, Iowa, 52242, United States

Location

University of Minnesota Medcical Center

Minneapolis, Minnesota, 55455, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Related Links

• Big Ten Cancer Research Consortium Website

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: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

(317) 634-5842

Study Officials

• Greg Durm, M.D.

  Big Ten Cancer Research Consortium

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: March 14, 2017
• First Posted: March 20, 2017
• Study Start: March 20, 2017
• Primary Completion: December 14, 2021
• Study Completion: March 3, 2022
• Last Updated: August 24, 2023
• Results First Posted: June 28, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)