Immune checkpoint inhibitors used in the neoadjuvant setting may enhance systemic immunity to prevent tumor recurrence, and previous data suggest administration in the preoperative setting is safe. CheckMate 358 explored the safety and feasibility of neoadjuvant nivolumab in patients (pts) with resectable human papillomavirus (HPV)+ or HPV− SCCHN.
This cohort is part of an ongoing global, multicenter study of virus-associated cancers (CheckMate 358; NCT02488759). Pts were PD-L1–unselected with newly diagnosed, previously untreated, resectable, HPV+ or HPV− SCCHN of the oral cavity, pharynx, or larynx with T1 or greater primary lesions and N1 or greater nodal disease. Pts were to receive nivolumab 240 mg on days 1 and 15 and surgery on day 29 ± 7. Tumor assessments by CT scan occurred at screening, presurgery, and during follow-up. Pretreatment tumor biopsies, surgical specimens, and peripheral blood were collected. Primary endpoints were safety (incidence of TRAEs) and delay >4 weeks from planned surgical date due to TRAEs. Investigator-assessed change in tumor dimensions was an exploratory endpoint. Additional assessments include pathologic response, tumor PD-L1 expression, and immune correlates. Preliminary results from a Feb 2017 database lock are reported.
Of 29 pts enrolled, 12 had HPV+ tumors and 17 HPV−. Median (range) follow-up was 22 (2–41) wks (HPV+) and 12 (4–56) wks (HPV−). All pts received both doses of nivolumab. Grade 3–4 TRAEs occurred in 2 (16.7%) pts with HPV+ tumors (lipase increased; glossodynia) and 2 (11.8%) pts with HPV− tumors (lipase increased); no new safety signals were identified. TRAEs did not result in any protocol-defined surgery delays. As of database lock, presurgery tumor reduction per CT scan was observed in 11 of 23 (48%) evaluable pts (5/10 HPV+ and 6/13 HPV−); 3 pts had tumor reduction ≥40% (largest reduction, 75%).
This is the first report of a global trial of neoadjuvant anti–PD-1 therapy in pts with both HPV+ and HPV− SCCHN. Nivolumab was well tolerated, with no surgery delay due to TRAEs. Nivolumab led to tumor reductions within 1 month in nearly half of evaluable pts.
Clinical trial identification
Legal entity responsible for the study
R.L. Ferris: Other from Amgen, Astra-Zeneca/MedImmune, Bristol-Myers Squibb, EMD Serono, Lilly, Merck, Pfizer, VentiRx Pharmaceuticals, outside the submitted work. S.S. Baxi: Consulting fees from BMS, outside the submitted work. U.M. Martens: Personal fees from Bristol-Myers Squibb, Roche, EMD Serono, Amgen, outside the submitted work. W.C. Spanos: Personal fees from BMS, Merck, outside the submitted work. R.S. Leidner: Research support from BMS, MedImmune/AstraZeneca. H. Kang: Grants and non-financial support (to institution) from BMS, during the conduct of the study; grants from Merck, Novartis, Plexxikon, Advaxis, Immunogen, VentiRx Pharmaceuticals, AstraZeneca, outside the submitted work (to institution). J. Russell: Consulting for EMD Serono. I. Soumaoro, S. Rao, Z.A. Cao: Employee of Bristol-Myers Squibb. S. Topalian: Grants and non-financial support from BMS; personal fees from Amgen, MedImmune/AstraZeneca, Merck, Pfizer, AbbVie; Personal fees & other from Five Prime Therapeutics, Jounce Therapeutics; Grants, personal fees & other from Potenza Therapeutics. All other authors have declared no conflicts of interest.