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

NCT ID: NCT06731413

Last Updated: 2025-02-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-11
• Study Completion Date: 2033-07-30

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.

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.

Conditions

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

Study Design

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

Study Groups

Reduced Dose Combination Therapy

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

Group Type: EXPERIMENTAL

Reduced Dose of Chemotherapy and Immunotherapy

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) (either squamous or non- squamous)
• Stage 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
• 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

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

Sponsors

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jonathan Berkman, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Massey IIT Research Operations

Role: CONTACT

masseyepd@vcu.edu

804-628-6430

Facility Contacts

Massey Lung Team

Role: primary

masseylung@vcu.edu

804-628-6430

Other Identifiers

MCC-24-21788

Identifier Type: -

Identifier Source: org_study_id