Recurrent and metastatic (R/M) SCCHN outcomes are generally poor and new treatments are needed. An ongoing phase I/II, multicenter, open-label study (NCT01693562) is evaluating the safety and efficacy of durvalumab (D), a human lgG1 mAb that blocks PD-L1 binding to PD-1 with high affinity and selectivity, in multiple solid tumor types including SCCHN. PD-L1 is expressed in SCCHN tumors and is associated with response to anti-PD-L1 treatment.
Pts with R/M SCCHN, an ECOG of 0 or 1, and no prior anti-PD-1/PD-L1 exposure are eligible. D is given every 2 weeks IV at 10 mg/kg for 12 months. Retreatment is permitted upon progression after 12 months. Safety data and efficacy data (DoR and PFS/OS) included have more mature follow up than previously reported (Segal, N et al. Poster presented at ASCO 2015, 3011).
As of 29 Apr 2016, 62 pts (mean age 58 years [range 24-96]; 86% male; 63% current/prior smokers; ECOG 0/1: 38%/62%; HPV pos/neg/unk: (40.3%/40.3%/19.4%), PD-L1 pos/neg/unk: (34%/61%/5%), had received a median of 3 prior systemic treatments (1-13)). Median duration of follow-up was 25.0 (range 1.4 – 31.6) months. The most frequent drug-related AEs were fatigue (18%), diarrhea, (8%), and nausea (8%). Five pts (8%) had AEs ≥Gr3 and there were no drug-related AEs leading to death. Among seven responders, six patients had DoR for >= 12 months with longest DoR being 19.8 months. Six and 12-month OS is 62% (95% CI 48, 74) and 42% (95% CI 27, 55), respectively. Preliminary analysis revealed no clear difference in OS by PD-L1 status.
In this updated report, the safety profile of D in SCCHN is consistent with previous reports. Responses are durable; landmark OS rates are encouraging in this heavily pre-treated population. A registration program is underway in pts with SCCHN for D alone and in combination with tremelimumab.
Clinical trial identification
Legal entity responsible for the study
N.H. Segal: Consultancy (including Ad Boards): Medimmune/AZ, BMS, Roche, Pfizer Research Funding: Medimmune/AZ, Roche, Pfizer, Merck. S-H.I. Ou: Consulting/advisory: ARIAD, Pfizer, Roche, AstraZeneca Speaker bureau: Roche, AstraZeneca, Boehringer Ingelheim Research funding: ARIAD, Boehringer Ingelheim, Pfizer, Ignyta, Daiichi Sankyo, Clovis. A.S. Balmanoukian: Speaker Bureau: BMS, Merck Research funding: Medimmune, Merck, Genentech, BMS, Merck Serono. E. Massarelli: Consulting/Advisory: Nektar Pharmaceuticals Research funding: AstraZeneca, Janssen, Clovis, Novartis, Astellas, Merck, Celgene. J.R. Brahmer: Consulting/advisory: AstraZeneca/Medimmune Research funding: AstraZeneca/Medimmune. J. Weiss: Consulting/Advisory: Pfizer, Biodesix, Clovis, AstraZeneca, Oncoplex Diagnostics, Lilly, EMD Serono Research funding: Merck, Acceleron Pharma, Astellas Pharma, Celgene, GSK, Medimmune, Pfizer. P. Schoffski: H: Medpace DS C/A: Swed Orphan Biovitrium (SOB) Blueprint Med (BM) Bayer BI, Piqur Eisai (E) EL Adatimm AZ Philogen Amcure Novartis (N) Cristal T SB: SOB N E GSK Bayer EL RF: Bayer GSK N Cobiores Exelixis Plexxikon BM T/A: PharmaMar. S.J. Antonia: Consulting/Advisory: BMS, AZ, Merck. D.P. Zandberg: Research funding: MacroGenics, Medimmune, AZ Travel, accommodation, expenses: AZ S. Khleif: Leader/stock: Advaxis Honor: MEDI, AZ, NewLink, Advaxis, Lucena, PDS Consult/AB: Gilead, Janssen, Nektan, Merus, GHI, BI Res fund: MEDI, AZ, NewLink, Advaxis, PDS, Serono, IOBiotech, Caretech, Medivation Travel: MEDI, AZ, Neulink, Advaxis, Lucena. X. Jin: Employment: United Health Care, Medimmune Stock/other ownership: AZ, United Health group M. Rebelatto: Employee of MedImmune LLC and hold stocks or shares in AstraZeneca K. Steele: Employment: Medimmune Stock/other ownership: AZ. J. Antal: Employment: Medimmune Stock/other ownership: AZ, GSK. A. Gupta: Employment: Medimmune Stock/other ownership: BMS, AZ Patents/Royalties/IP: BMS. All other authors have declared no conflicts of interest.