Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Older Adults w/Adv <50% PD-L1 Non-Small Cell Lung Cancer (NSCLC)

Phase 2 Study to Evaluate Reduced Dose Chemotherapy in Combination With Anti-PD-1 Therapy as First Line Treatment in Vulnerable or Older Adults (Vulnerable or Age ≥70) With Advanced PD-L1 TPS <50% Non-small Cell Lung Cancer

Evaluate frequency of adverse events that lead to chemotherapy discontinuation in vulnerable older adults with recurrent/metastatic PD-L1 TPS<50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer; NSCLC; Advanced Non-Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Reduced Dose of Chemotherapy and Immunotherapy

Detailed Description

This is a single institution, single arm, open label phase 2 study in vulnerable or older adults (Age ≥70) with recurrent or metastatic, histologically confirmed squamous cell carcinoma or non-squamous cell carcinoma of lung without driver mutation and PD-L1 TPS < 50% to evaluate safety and tolerability of reduced dose of chemotherapy and immunotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Massey IIT Research Operations; Phone Number: 804-628-6430; Email: masseyepd@vcu.edu

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Massey Lung Team; Phone Number: 804-628-6430; Email: masseylung@vcu.edu
      • Principal Investigator: Jonathan Berkman, MD
    • Tappahannock, Virginia, United States, 22560
      • Recruiting
      • VCU Health Tappahannock Hospital
      • Principal Investigator: Jonathan Berkman, MD
      • Contact: Massey CTO Lung Team; Phone Number: 804-628-6430; Email: masseylung@vcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous)
• Stage IIIB, IIIC or IV disease OR have recurrent disease and not be candidates for curative treatment such as combined chemo-radiation
• No previous line of treatment in the recurrent or metastatic setting. Neoadjuvant or adjuvant treatment more than 6 months before enrollment is acceptable.
• Age 70 or meeting frailty definition or above at the date of signing informed consent
• Absence of driver mutations that have first line Food and Drug Administration (FDA) approved targeted therapy (biomarker testing is optional for squamous cell)
• PD-L1 tumor proportion score (TPS) of less than 50%
• Eastern Cooperative Oncology Group (ECOG) PS of 0-3
• Have measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment
• Absolute neutrophil count (ANC) ≥ 1,000/μL
• Platelets ≥ 75,000/μL
• Hemoglobin (Hgb) ≥ 8.0 g/dL (transfusion permitted)
• Total bilirubin ≤ 2 x institutional upper limit of normal (ULN)
• Aspartate amino transferase (AST)serum glutamic-oxaloacetic transaminase (SGOT) /alanine aminotransferase (ALT)serum glutamic-pyruvic transaminase (SGPT) ≤ 5.0 × institutional ULN
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Participants with life expectancy of less than 3 months at the time of enrollment
• Has active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, or immunosuppressive drugs)
• Diagnosis of interstitial lung disease
• Creatinine clearance of <30 mL/min
• Symptomatic, untreated central nervous system (CNS) disease or leptomeningeal disease. Patients with asymptomatic or treated CNS disease are eligible

• Required ongoing use of immunosuppressive medication, including steroids, with the following allowable exceptions:

  • Doses less than or equal to the equivalent of prednisone 10 mg daily
  • Short courses of steroids that are discontinued prior to enrollment
  • Inhaled, intranasal and/or topical steroids
  • Dexamethasone taper for treating vasogenic edema associated with CNS disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Reduced Dose Combination Therapy; Squamous cell histology: Carboplatin AUC 3 every 21 days IV for 4 cycles; Paclitaxel 135 mg/m2 every 21 IV days for 4 cycles; Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles Non-squamous histology: Carboplatin AUC 3 every 21 days IV for 4 cycles; Pemetrexed 375 mg/m2 every 21 IV days for 4 cycles; Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles

Drug: Reduced Dose of Chemotherapy and Immunotherapy; Eligible participants with recurrent or metastatic squamous cell carcinoma will receive 4 cycles of carboplatin area under the curve (AUC) 3 IV every 21 days and paclitaxel 135 mg/m2 intravenous (IV) every 21 days. Participants with non-squamous histology will receive carboplatin AUC 3 IV every 21 days and pemetrexed 375 mg/m2 IV every 21 days (collectively, induction chemotherapy). Both groups will receive pembrolizumab 200 mg IV every 21 days for a total of up to 35 cycles (Cycles ≥5 are collectively the maintenance portion of treatment) or until disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of chemotherapy discontinuation due to treatment-related adverse events	Evaluate treatment tolerability i by the number of participants that discontinue chemotherapy treatment due to treatment-related adverse events.	Through completion of protocol therapy, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response (complete response and partial response) per Response Evaluation Criteria in Solid Tumors	Evaluate overall response defined by complete and partial response in vulnerable or older adults with recurrent/metastatic PD-L1 TPS <50% NSCLC patients who receive reduced dose chemotherapy in combination with immunotherapy per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to 5 years
Overall incidence and severity of all adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0	The total number of AE's recorded for the protocol.	Time of patient consent and throughout the duration of the study, including during the treatment period and for 30 days following the final dose of the study medication, up to 2 years and 1 month
Overall survival defined as the time from the date of first study treatment until the date of death. Overall survival (OS) will be censored on the last date a participant was known to be alive	Overall survival of participants measured in days.	Up to 5 years
Progression-free survival (PFS) measured from the date of first study treatment until the date of documented disease progression	Evaluate progression-free survival of participants in days utilizing RECIST 1.1 criteria or death from any cause, whichever occurs first.	Up to 5 years
Cancer related symptoms and quality of life	Evaluate impact of the reduced dose combination therapy on quality of life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ C30). The EORTC QLG Core Questionnaire (EORTC QLQ-C30) is a 30 item instrument meant to assess some of the different aspects that define the quality of life of cancer patients.The functioning and the global QoL scales, a higher score indicates better health. Response options are on a 4-point Likert-type scale (not at all; a little; quite a bit; very much) and a 7-point Likert scale for global HRQoL ranging from 'Very poor' to 'Excellent'. The QLQ-C30 summary score is calculated as the mean of the combined 13 QLQ-C30 scale and item scores with a higher score indicating a better HRQoL.	Baseline, Cycle 3 Day 1, Cycle 5 Day 1 Cycle 9 Day 1, EOT Visit (up to 2 years)

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Jonathan Berkman, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2025
• Primary Completion (Estimated): July 30, 2030
• Study Completion (Estimated): July 30, 2033

Study Registration Dates

• First Submitted: December 6, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer, NSCLC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Biological Therapy; Immunomodulation; Immunotherapy
• Other Study ID Numbers: MCC-24-21788

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Currently there are no plans to share IPD with other researchers.

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