Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) expansion cohort

Date

10 Oct 2016

Session

Head and neck cancers

Presenters

Neil Segal

Citation

Annals of Oncology (2016) 27 (6): 328-350. 10.1093/annonc/mdw376

Authors

N.H. Segal1, S.I. Ou2, A.S. Balmanoukian3, E. Massarelli4, J.R. Brahmer5, J. Weiss6, P. Schoffski7, S.J. Antonia8, C. Massard9, D.P. Zandberg10, C. Maher1, S. Khleif11, X. Jin12, M. Rebelatto13, K. Steele13, J. Antal14, A. Gupta14, A. Spreafico15

Author affiliations

  • 1 Department Of Medicine, Memorial Sloan Kettering Cancer Center, NY 10065 - New York/US
  • 2 Department Of Medicine, Division Of Hematology/oncology, UC Irvine School of Medicine, Irvine/US
  • 3 Medical Oncology, The Angeles Clinic and Research Institute, Los Angeles/US
  • 4 Department Of Thoracic And Head/neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 5 Department Of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore/US
  • 6 Division Of Hematology And Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill/US
  • 7 Department Of General Medicine Oncology, University Hospitals Leuven, Leuven/BE
  • 8 Department Of Thoracic Oncology, Moffitt Cancer Center, Tampa/US
  • 9 Drug Development Department, Institut Gustave Roussy, Villejuif/FR
  • 10 Medical Oncology, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore/US
  • 11 Immune Therapy Program And Experimental Therapeutics, Georgia Regents University Cancer Center, Augusta/US
  • 12 Biostatistics, Medlmmune, Gaithersburg/US
  • 13 Pathology, Medlmmune, Gaithersburg/US
  • 14 Clinical Development, Medlmmune, Gaithersburg/US
  • 15 Division Of Medicine Department Of Medical Oncology And Hematology Drug Development Program, Princess Margaret Cancer Centre, Toronto/CA
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Background

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.

Methods

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).

Results

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.

Conclusions

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

NCT01693562

Legal entity responsible for the study

MedImmune LLC

Funding

MedImmune

Disclosure

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.

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