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Proffered paper session - Head and neck cancer

4263 - M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-_, in patients (pts) with advanced SCCHN: results from a phase 1 cohort


22 Oct 2018


Proffered paper session - Head and neck cancer


Clinical Research;  Immunotherapy

Tumour Site

Head and Neck Cancers


Byoung Chul Cho


Annals of Oncology (2018) 29 (suppl_8): viii372-viii399. 10.1093/annonc/mdy287


B.C. Cho1, A. Daste2, A. Ravaud2, S. Salas3, N. Isambert4, E. McClay5, A. Awada6, C. Borel7, J. Gulley8, L. Ojalvo9, C. Helwig10, P..A. Rolfe11, N. Penel12

Author affiliations

  • 1 Medical Oncology, Yonsei Cancer Center Yonsei University, 6273 - Seoul/KR
  • 2 Medical Oncology, CHU Bordeaux Hopital St. André, 33000 - Bordeaux/FR
  • 3 Medical Oncology, CEPCM Assistance Publique des Hôpitaux de Marseille, 13385 - Marseille/FR
  • 4 Medical Oncology, Centre Georges-François Leclerc (Dijon), 21079 - Dijon/FR
  • 5 Medical Oncology, Institute for Melanoma Research & Education, California Cancer Associates for Research & Excellence, Inc, 92024 - Encinitas/US
  • 6 Medical Oncology Clinic, Institut Jules Bordet, Université Libre de Bruxelles, 1000 - Brussels/BE
  • 7 Medical Oncology, Centre Paul Strauss Centre de Lutte contre le Cancer, 67065 - Strasbourg/FR
  • 8 Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, 20892 - Bethesda/US
  • 9 Immuno-oncology, EMD Serono, Billerica/US
  • 10 Biostatistics, Merck KGaA, Darmstadt/DE
  • 11 Bioinformatics Immunology And Immuno-oncology, EMD Serono, Billerica/US
  • 12 General Oncology Department, Centre Oscar Lambret, 59020 - Lille/FR


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Abstract 4263


The TGF-β pathway promotes tumor immunosuppression, and its inhibition may enhance the antitumor activity of PD-(L)1 mAbs. M7824 is an innovative first-in-class bifunctional fusion protein composed of an anti–PD-L1 mAb fused with the extracellular domain of TGF-βRII (a TGF-β “trap”). We report results in pts with Stage III/IV ≥2L SCCHN not amenable to local therapy with curative intent that progressed/recurred <6 months since last platinum dose.


In the phase 1 trial NCT02517398, pts with SCCHN received M7824 1200 mg q2w until confirmed PD, unacceptable toxicity, or trial withdrawal; continuation of M7824 beyond PD was permitted if AEs were manageable, PS maintained and no new treatment indicated. Biomarkers include tumor cell PD-L1 level (antibody clone 73-10) and HPV status (by RNAseq). The primary endpoint is BOR per RECIST; secondary endpoints include safety/tolerability.


As of 12 March 2018, 32 pts (75% had ≥2 prior lines of therapy) received M7824 for a median duration of 12.1 (range, 2–74) weeks. 5 pts had a confirmed PR by investigator read (RECIST v1.1 ORR 15.6%). 2 additional pts developed delayed PRs after initial increase in index lesions per RECIST (total ORR 21.9%). 6 pts had SD (total DCR 40.6%). 4/5 pts with PR (DOR 4.1–12.5+ months) and both pts with PD→PR remain on treatment. The ORR (including pts with PD→PR) in HPV+ was 50% (4/8; HPV- ORR 13.6% [3/22]). PD-L1 expression was not predictive for ORR (20% [5/25 pts)] in PD-L1≥1%; 33% [2/6] in PD-L1<1%). 12-month OS rate was 51.2%. 10 pts (31.3%) had grade 3 TRAEs (increased liver enzymes [3 pts], hyperglycemia, maculopapular rash [2 pts each], anemia, hyperthyroidism, diabetic ketoacidosis + hypothyroidism, keratoacanthoma + folliculitis, skin SCC [1 pt each]); there were no grade 4 TRAEs and no treatment-related discontinuations or deaths.


M7824 showed promising early clinical activity and a manageable safety profile in pts with refractory/metastatic ≥ 2L SCCHN. A total ORR of 21.9% was observed (including 2 pts with initial tumor growth), with a possible trend toward higher activity in HPV + (ORR 50%) and evidence of clinical activity irrespective of PD-L1 status.

Clinical trial identification


Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.


Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

Medical writing support was provided by ClinicalThinking and funded by Merck KGaA, Darmstadt, Germany.


N. Isambert: Travel, accommodations, expenses: Roche, MedImmune, AstraZeneca, Novartis, Celgene, Pharmara. E. McClay: Honoraria: Genentech, Bristol-Myers Squibb; Speakers bureau: Genentech, Bristol-Myers Squibb, Merck. C. Borel: Honoraria: Merck, Bristol-Myers Squibb, AstraZeneca, Amgen; Consultancy: Bristol-Myers Squibb, AstraZeneca; Travel, accommodations, expenses: Merck. L. Ojalvo: Employment: EMD Serono. C. Helwig: Employment: Merck KGaA; Equity ownership: Merck KGaA. P.A. Rolfe: Employment: EMD Serono. All other authors have declared no conflicts of interest.

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