TRIPL: Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer
Montefiore Medical Center
Summary
Determine anti-tumor efficacy by characterizing response rates on positron emission tomography (PET) following three cycles of induction immunotherapy with cemiplimab and fianlimab without chemotherapy for locally advanced non-small cell lung cancer (LA-NSCLC).
Description
Non-small cell lung cancer (NSCLC) represents more than 80% of lung cancers, and approximately 35% of NSCLC patients present with stage III disease. Standard treatment for patients with locally advanced NSCLC, which may be defined as American Joint Committee on Cancer (AJCC) stage III disease or unresectable stage II disease, typically consists of conventionally fractionated (1.8-2.0 Gray (Gy) per day) radiotherapy (RT) to a total dose of approximately 60 Gy with concurrent chemotherapy. Based on the PACIFIC trial (NCT02125461), patients without disease progression after concurrent chemoradiot…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Previously untreated and biopsy-proven NSCLC, with measurable disease (at least 1 unidimensional, radiographically measurable lesion based on RECIST v1.1) and one of the following stages: (prior resection or stereotactic radiotherapy for early-stage disease is allowed) * AJCC version 8 Stage II disease, medically or technically unresectable * AJCC version 8 Stage III disease, eligible for non-surgical treatment * Determination of PD-L1 expression on pretreatment tumor specimen using a clinically validated assay * Eligible for standard nonsurgical treatment for Stage…
Interventions
- DrugCemiplimab
Human IgG anti-PD-1 monoclonal antibody approved for treatment of advanced NSCLC with PD-L1 TPS ≥ 50% as monotherapy and in combination with chemotherapy
- DrugFianlimab
Human IgG anti-lymphocyte activation gene 3 (LAG-3) monoclonal antibody, which is expressed by various immune cells, and regulates effector T-cell activation and responses. LAG-3 inhibition restores the effector function of exhausted T cells, enhancing their ability to attack tumor cells. Fianlimab is currently under investigation in several clinical studies involving NSCLC (NCT05800015, NCT03916627, NCT05785767).
- RadiationRadiotherapy
Thoracic radiotherapy. Conventionally fractionated 1.8-2.0 Gray (Gy) per day. Adaptive radiotherapy will not be performed unless difficulty with patient setup or changes in internal patient anatomy require repeating the CT simulation procedure
- DrugPlatinum Doublet Chemotherapy (PDC)
Acceptable histology-specific PDC regimens include carboplatin plus paclitaxel or nab-paclitaxel (any histology), carboplatin/cisplatin plus pemetrexed (nonsquamous), carboplatin/cisplatin plus etoposide (any histology), and carboplatin/cisplatin plus docetaxel or gemcitabine (squamous). Carboplatin can be used instead of cisplatin after cycle 1 in cases of cisplatin-induced neuro-/oto-/nephrotoxicity as long as the patient remains eligible for chemoradiotherapy. Weekly radiosensitizing PDC will be recommended for PD-L1 TPS \<50% patients during RT but is not required.
Location
- Montefiore Einstein Comprehensive Cancer Center (MECCC)The Bronx, New York