The TRIPL trial (NCT06865339) is testing thoracic radiotherapy combined with dual PD-1 and LAG-3 blockade, using cemiplimab (Libtayo) plus the investigational LAG-3 inhibitor fianlimab, in patients with locally advanced non-small cell lung cancer (NSCLC).1 The trial builds on the SPRINT trial (NCT03523702), which combined radiotherapy with pembrolizumab (Keytruda) and produced a 1-year progression-free survival rate of 76%, though some patients still experienced disease recurrence.2 Additionally, the regimen produced 1- and 2-year overall survival rates of 92% and 76%, respectively. Investigators concluded that pembrolizumab plus risk-adapted radiation may be a promising approach for patients with locally advanced NSCLC.
Nitin Ohri, MD, MS, a professor of radiation oncology at Montefiore Einstein Comprehensive Cancer Center in the Bronx, New York, spoke with CancerNetwork® at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting, as the TRIPL trial’s principal investigator, about the biological rationale for adding a second checkpoint target rather than simply intensifying PD-1 blockade alone. Based on previous data showing that using higher doses of the same drugs may not improve outcomes, Ohri noted that attacking the disease with 2 different checkpoint inhibitors may be a promising approach.
