Reduced CT + Anti-PD-1 as First Line Tx in Vulnerable Old... | NCT06731413

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Reduced Dose Combination Therapy	Experimental	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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

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 Outcomes

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

Eligibility Module

Eligibility Criteria

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

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases