Recruiting
Phase 2

Reduced CT & Anti-PD-1

Sponsor:

Virginia Commonwealth University

Code:

NCT06731413

Conditions

Non-Small Cell Lung Cancer

NSCLC

Advanced Non-Small Cell Lung Cancer

Metastatic Non Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Reduced Dose of Chemotherapy and Immunotherapy

Study Details

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

NSCLC

Advanced Non-Small Cell Lung Cancer

Metastatic Non Small Cell Lung Cancer

Study ID

NCT06731413

Start date

Feb 11, 2025

Status verified date

May, 2026

Completion date

Jul 30, 2033

Anticipated

Primary completion date

Jul 30, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

40 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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

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.

Primary outcome measure

  • Occurrence of chemotherapy discontinuation due to treatment-related adverse events [ Time Frame: Through completion of protocol therapy, up to 2 years ]

Central Contacts and Locations

Central contacts

Massey IIT Research Operations

804-628-6430masseyepd@vcu.edu

Locations

Virginia Commonwealth University

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Massey Lung Team

804-628-6430masseylung@vcu.edu

Principal Investigator:

Jonathan Berkman, MD

VCU Health Tappahannock Hospital

Recruiting

Tappahannock, Virginia, United States, 22560

Contacts

Massey CTO Lung Team

804-628-6430masseylung@vcu.edu

Principal Investigator:

Jonathan Berkman, MD

More Information

Sponsor

Virginia Commonwealth University

Last update posted

Jun 2, 2026

Last verified

May, 2026

Keywords

  • Non-Small Cell Lung Cancer, NSCLC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Virginia Commonwealth University on 2026-06-02.