R/M SCCHN causes substantial morbidity and mortality, with a median overall survival (OS) of less than 12 months (mo). Thus, improvement in the standard of care is needed. Nivo, a fully human IgG4 monoclonal antibody to the PD-1 receptor, has shown increased OS in pts with solid tumors, including SCCHN. The combination of nivo with ipi (a humanized IgG1 CTLA-4 checkpoint inhibitor) is approved in advanced melanoma and has demonstrated clinical activity and manageable safety in various solid tumors. This randomized, double-blind, two-arm, phase 2 study will examine the safety and efficacy of nivo combined with ipi vs nivo alone when given as 1L therapy in pts with R/M SCCHN. Also underway, a companion randomized, open-label, phase 3 study (CheckMate 651; NCT02741570) will compare nivo combined with ipi vs the Extreme regimen (cetuximab + cisplatin/carboplatin + fluorouracil) as 1L therapy in pts with R/M SCCHN.
Eligible pts include those aged ≥18 years with histologically confirmed untreated R/M SCCHN not amenable to curative therapy. Pts will be screened as platinum eligible (no prior systemic therapy except as adjuvant or neoadjuvant, or chemotherapy as part of multimodal treatment for locally advanced disease [LAD] completed >6 mo prior) or platinum refractory (relapse within 6 mo after platinum therapy in adjuvant or LAD setting). Approximately 315 pts will be stratified by PD-L1 status, HPV p16 status (oropharyngeal cancer pts only), and platinum-refractory subgroup status, then randomized (2:1) to receive nivo every 2 wks (Q2W) + ipi every 6 wks (Q6W) or nivo Q2W + intravenous PBO Q6W. Treatment will continue until progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR; RECIST v1.1 criteria) in platinum-refractory pts. Secondary endpoints include ORR in the platinum-eligible subgroup, progression-free survival and OS in platinum-refractory and -eligible subgroups, and ORR by PD-L1 expression and HPV p16 status. Exploratory endpoints include safety and pt-reported outcomes.
Clinical trial identification
We are pleased to submit to the European Society for Medical Oncology (EMSO) our abstract entitled “Double Blind, Two-Arm, Phase 2 Study of Nivolumab (nivo) in Combination With
Ipilimumab (ipi) Versus Nivo and Ipi-Placebo (PBO) as First-Line (1L) Therapy in Patients (pts) With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (R/M SCCHN). [CheckMate 714].” Checkmate 714 is a randomized, double-blind, two-arm, phase 2 study that will examine whether nivo combined with ipi will improve survival and response rate compared with nivo alone when given as first-line therapy in pts with R/M SCCHN (NCT registration number to be provided upon confirmation). We recognize that it is ESMO policy for Trial in Progress submissions to have recruitment begun or completed by the abstract submission deadline of May 11 2016. However, in order to rapidly communicate an awareness of this trial, we would kindly ask for an exception to this policy. We expect a first patient first visit timing of August 2016, which would precede a presentation of the trial at ESMO in October 2016.
Thank you for your consideration.
With best regards,
Legal entity responsible for the study
Sponsored by Bristol-Myers Squibb.
Sponsored by Bristol-Myers Squibb.
R. Haddad: Clinical trial support to institution, advisory board, consulting from BMS. Grants from Astra Zeneca, Celgene, Venti-Rx. Personal fees from Merck, Pfizer, Celgene, Eisai. M. Gillison: Consulting and Clinical Trials Contract to OSU from BMS. R.L. Ferris: Grants from VentiRx. Paid Member of Advisory Board(AdHoc) for Merck, Celgene, AZ/Medimmune, and BMS. K. Harrington: Advisory Board member for BMS, Astra-Zeneca, Merck and Pfizer. M. Monga, C. Baudelet: Employee of BMS. A. Argiris: Consultant for BMS. All other authors have declared no conflicts of interest.