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

NCT06731413 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-24-21788
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer; Advanced Non-Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer; NSCLC

Keywords

Non-Small Cell Lung Cancer, NSCLC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Response (complete response and partial response) per Response Evaluation Criteria in Solid Tumors

  Up to 5 years

• Overall incidence and severity of all adverse events assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  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

  Up to 5 years

• Progression-free survival (PFS) measured from the date of first study treatment until the date of documented disease progression

  Up to 5 years

• Cancer related symptoms and quality of life

  Baseline, Cycle 3 Day 1, Cycle 5 Day 1 Cycle 9 Day 1, EOT Visit (up to 2 years)

Study Arms (1)

Reduced Dose Combination Therapy

EXPERIMENTAL

Squamous cell histology: 1. Carboplatin AUC 3 every 21 days IV for 4 cycles 2. Paclitaxel 135 mg/m2 every 21 IV days for 4 cycles 3. Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles Non-squamous histology: 1. Carboplatin AUC 3 every 21 days IV for 4 cycles 2. Pemetrexed 375 mg/m2 every 21 IV days for 4 cycles 3. Pembrolizumab 200 mg every 21 days IV until disease progression or unacceptable toxicity up to 35 cycles

Drug: Reduced Dose of Chemotherapy and Immunotherapy

Interventions

Reduced Dose of Chemotherapy and Immunotherapy DRUG

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.

Reduced Dose Combination Therapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Jonathan Berkman, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massey IIT Research Operations

CONTACT

804-628-6430; masseyepd@vcu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 12, 2024
• Study Start: February 11, 2025
• Primary Completion (Estimated): July 30, 2030
• Study Completion (Estimated): July 30, 2033
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)