NSCLC is the most common cause of cancer-related death. Even clinical stage I or II tumors that are completely resected harbor a 5-year survival of only 30-50%. Immunotherapy is being investigated now as adjuvant therapy and might improve those results. We hypothesize that neo-adjuvant immunotherapy is a feasible, safe and effective treatment for early stage NSCLC.
MK3475-223 is a phase I study, testing neoadjuvant Pembro for stage I and II NSCLC. Study design is based on a classical 3 + 3 cohort, but the differences between cohorts are not drug dose but number of treatments (1st cohort 1 treatment, 2nd and 3rd cohorts 2 treatments with a 3 weeks (wk) interval between them) prior to surgery, and interval from last dose to surgery (1st cohort 3 wks, 2nd cohort 2 wks, 3rd cohort 1 wk). All Pembro treatments are 200mg. Primary objectives are to determine safety, recommended phase 2 dose/schedule, pathological and radiological response. Dose limiting toxicities (DLT) were defined as significant surgical complications (bleeding, delayed wound healing, acute respiratory distress syndrome, prolonged air-leak) or a significant delay of surgery. DLT period was defined as 30 days post-surgery.
To date, two cohorts (6 patients (pts)) have been fully recruited and completed the DLT period. No DLT has occurred. Adverse events (AEs) are within the recognized AE profile of Pembro and of thoracic surgical procedures. No significant responses were seen in the 1st cohort (1 Pembro treatment, 3 wks later surgery). Out of 3 pts on the 2nd cohort (2 Pembro treatments, 2 wks later surgery), 2 pts (66.6%) demonstrate near complete pathologic response, with less than 1% of tumor cells left estimated. The study is ongoing and continuing to recruit, currently recruiting the final cohort (2 pembro treatments, 1 wk later surgery), to be followed by an expansion cohort.
Neoadjuvant Pembro is a promising option for early stage NSCLC. Initial data suggest the safety of this approach. The trial will provide initial evidence as well as correlative studies regarding the efficacy of this approach.
Clinical trial identification
Legal entity responsible for the study
Sheba Medical Center.
J. Bar: Consultant fees: Roche, Boehringer Ingelheim, Novartis, BMS, MSD, Pfizer, AstraZeneca, Takada, Abbvie, VBL; Grant support: Boehringer Ingelheim, AstraZeneca, MSD. All other authors have declared no conflicts of interest.