Study of Pembrolizumab With Single Agent Chemotherapy in Elderly Patients With Advanced NSCLC (HFHS 21-01)

Phase II Study of Pemetrexed or Nab-paclitaxel With Pembrolizumab in Elderly (>/= 75 Years) Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

This Phase II trial is to see how well single agent chemotherapy and pembrolizumab work elderly patients (≥ 75 years) with advanced non small cell lung cancer (NSCLC). Pembrolizumab stimulates your immune system to help fight lung cancer. This treatment approach may be better tolerated in elderly patients.

Study Overview

• Status: Withdrawn
• Conditions: Non Small Cell Lung Cancer; PD-L1 Gene Mutation; Advanced Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Pembrolizumab; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Nab-paclitaxel

Detailed Description

Primary Objective(s), Hypothesis(es), and Endpoint(s)

I. Objective: To evaluate the efficacy of single agent chemotherapy and pembrolizumab in elderly (≥ 75 years) advanced NSCLC patients Hypothesis: We propose that single agent chemotherapy with pembrolizumab will be better tolerated and will provide similar efficacy as platinum-based combination chemotherapy with pembrolizumab in advanced elderly (≥75 years) NSCLC patients.

Primary Endpoint:

I. Assess median PFS in elderly (≥ 75 years) advanced NSCLC patients with tumor PD-L1 (<50%) treated with pemetrexed or nab-paclitaxel and pembrolizumab.

Secondary Objective(s), Hypothesis(es), and Endpoint(s)

I. Objective: To assess additional measure of efficacy of the regimen. To define the toxicity of the regimen in addition

II. Hypothesis: In this patient population single agent chemotherapy and pembrolizumab will provide similar efficacy but improved tolerability as 2 drug combination with pembrolizumab.

Secondary Endpoints:

I. Assess overall survival in the study population II. Assess the toxicities with the study therapy and the rate of discontinuation of study therapy due to toxicities related to study therapy

Exploratory Objective:

I. Objective: To define correlatives that can identify patients most likely to benefit from the study therapy.

II. Correlate PFS with blood-based tumor mutational burden and ctDNA.

Participants who experience confirmed disease progression or start a new anticancer therapy, will move into the Survival Follow-Up Phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the trial, whichever occurs first.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years to 90 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male/female participants who are ≥75 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage IV (AJCC version 8) NSCLC with tumor PD-L1 < 50% and negative 'driver' alterations in EGFR, ALK and ROS1 will be enrolled in this study. Tumor PD-L1 expression should be assessed by FDA approved Dako 22C3 test.
2. Patients should be treatment naïve for stage IV NSCLC. Patients previously treated for earlier stages of lung cancer are eligible if they have not received systemic therapy for a minimum of 180 days prior to the start of study therapy.
3. The participant provides written informed consent for the trial.
4. Have measurable disease based on RECIST 1.1 or evaluable disease.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1. Evaluation of ECOG is to be performed within 7 days prior to the date of start of therapy.

6. Male participants:

   A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 180 days after the last dose of study treatment and refrain from donating sperm during this period.

7. Have adequate organ function as evidenced by laboratory assessment. Specimens must be collected within 10 days prior to the start of study treatment.

Exclusion Criteria:

1. Patient could not have received any anti-cancer systemic therapy for a minimum of 180 days prior to the start of study therapy. Patient should not have received prior PD-1 or PD-L1 therapy.
2. Has received prior definitive palliative radiotherapy within 2 weeks or definitive radiotherapy within 6 months of study intervention. Participants must have recovered from all radiation-related toxicities, require corticosteroids no more than 10 mg of prednisone or equivalent dose of other steroids, and not have had clinical radiation pneumonitis.
3. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
4. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
5. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

6. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Patients with cancers such as PSA only prostate cancer may be considered after discussion with the principal investigator.

   Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers

7. Has symptomatic CNS metastases and/or carcinomatous meningitis. Subjects with asymptomatic brain metastases may participate provided they are clinically stable and are not using steroids equivalent to >10mg of prednisone day prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of whether it is symptomatic or not.
8. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
9. 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 and is allowed.
10. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV testing is required unless mandated by local health authority.
13. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
14. Has a known history of active TB (Bacillus Tuberculosis).
15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
16. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
17. Has had an allogenic tissue/solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Pemetrexed; Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + pemetrexed 500mg intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21 day cycle up to 35 cycles or until disease progression.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pembrolizumab; PD-L1 inhibitor administered as an intravenous (IV) infusion.; Other Names: Keytruda; Drug: Pemetrexed; Folate analog metabolic inhibitor administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC; Other Names: ALIMTA
Experimental: Pembrolizumab + Paclitaxel OR Paclitaxel; Pembrolizumab 200mg intravenous (IV) infusion on Day 1 of each 21 day cycle. Treatment repeats every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity + Paclitaxel 100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle OR Paclitaxel100 mg/m2 intravenous (IV) infusion on days 1 and 8 of each 21 day treatment cycle until disease progression.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Pembrolizumab; PD-L1 inhibitor administered as an intravenous (IV) infusion.; Other Names: Keytruda; Drug: Paclitaxel; A novel antimicrotubular agent administered as an intravenous (IV) infusion single agent chemotherapy for advanced NSCLC; Other Names: TAXOL; Drug: Nab-paclitaxel; Microtubule inhibitor administered as an intravenous (IV) infusion indicated for the treatment of locally advanced or metastatic NSCLC; Other Names: ABRAXANE®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median progression free survival	Length of time treatment to disease progression	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from progression until death	12 months

Collaborators and Investigators

• Sponsor: Shirish Gadgeel
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Shirish Gadgeel, MBBS, Henry Ford Health System

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Paclitaxel; Pembrolizumab; Albumin-Bound Paclitaxel; Pemetrexed
• Other Study ID Numbers: HFHS 21-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data (IPD) will be shared with Dr. Muneesh Tewari's laboratory at University of Michigan for the CtDNA samples. Outside, of this IPD will be shared with Merck who is providing drug for this protocol. IPD will not be shared with any researchers outside of this. All subjects are assigned a study specific ID number. No direct patient identifiers leave the site.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes