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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

4393 - Updated results of M7824 (MSB0011359C), a bifunctional fusion protein targeting TGF-_ and PD-L1, in second-line (2L) NSCLC

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Topics

Clinical Research

Tumour Site

Presenters

Luis Paz-Ares

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

L. Paz-Ares1, T.M. Kim2, D. Vincente3, E. Felip4, D.H. Lee5, K.H. Lee6, C. Lin7, M.J.F. Oncala8, M. Di Nicola9, R.M. Alvarez10, I. Dussault11, C. Helwig12, L. Ojalvo13, J. Gulley14, B.C. Cho15

Author affiliations

  • 1 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2 Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 3 Medical Oncology, Hospital Univeritario Virgen Macarena, Seville/ES
  • 4 Medical Oncology Service (lung Cancer Unit)  , Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 5 Department Of Oncology, University of Ulsan College of Medicine, Seoul/KR
  • 6 Department Of Internal Medicine, Chungbuk National University Hospital, Chungcheongbuk-Do/KR
  • 7 Department Of Oncology, National Taiwan University Hospital, 100 - Taipei city/TW
  • 8 Medical Oncology, Hospital Universitario Virgen Del Rocio, Seville/ES
  • 9 Medical Oncology And Hematology, Istituto Nazionale dei Tumori di Milano - Fondazione IRCCS, 20133 - Milan/IT
  • 10 Department Of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid/ES
  • 11 Clinical Briomarkers, EMD Serono, Billerica/US
  • 12 Medical Oncology, Merck KGaA, Darmstadt/DE
  • 13 Immuno-oncology, EMD Serono, Billerica/US
  • 14 Genitourinary Malignancies Branch, National Cancer Institute, 20892 - Bethesda/US
  • 15 Medical Oncology, Yonsei Cancer Center Yonsei University, 6273 - Seoul/KR
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Resources

Abstract 4393

Background

2L+ overall response rates (ORRs) with PD-(L)1 inhibitors in patients (pts) with advanced NSCLC range from 12% to 19% (PD-L1 unselected), and median PFS ranges from 2.3 to 4.0 mo. Inhibiting the transforming growth factor β (TGF-β) pathway, which promotes tumor immunosuppression, may enhance the response to PD-(L)1 therapy. M7824 is an innovative first-in-class bifunctional fusion protein composed of a human IgG1 monoclonal antibody against PD-L1 fused with 2 extracellular domains of TGF-βRII (a TGF-β “trap”).

Methods

Pts with advanced NSCLC unselected for PD-L1 who progressed after 1L standard treatment (no prior immunotherapy) were randomized to receive M7824 500 or 1200 mg (n = 40 each) q2w until disease progression, unacceptable toxicity or trial withdrawal in this expansion cohort of the ongoing, phase 1 trial NCT02517398. The primary objective is to assess BOR per RECIST v1.1; other objectives are dose exploration and safety/tolerability. Tumor cell PD-L1 expression (Ab clone 73-10 [≥80% is comparable to ≥ 50% with 22C3]) was evaluable in 75 pts.

Results

As of March 12, 2018, 80 pts received M7824 for a median of 11.9 (range, 2-66.1) wk, with a median follow-up of 51.1 wk; 10 pts remain on treatment. Investigator-assessed confirmed ORR was 27.5% at 1200 mg and 20% at 500 mg. Clinical activity was observed across PD-L1 subgroups (Table); ORR was 40.7% in PD-L1 + (≥1%) and 71.4% in PD-L1–high (≥80%) pts at 1200 mg. The most common treatment-related adverse events (TRAEs) were pruritus (20%), maculopapular rash (18.8%), decreased appetite (12.5%) and asthenia (11.3%). Grade ≥3 TRAEs occurred in 23 pts (28.8%); 8 pts (500 mg, n = 2; 1200 mg, n = 6) discontinued treatment due to TRAEs. No treatment-related deaths occurred.Table: 1463P

ORR, n/N; %500 mg1200 mgTotal
All PD-L1+ PD-L1 high8/40; 20.0 6/31; 19.4 2/6; 33.311/40; 27.5 11/27; 40.7 5/7; 71.419/80; 23.8 17/58; 29.3 7/13; 53.8
Median PFS; OS, mo
All PD-L1+ PD-L1 high1.4; 10.9 1.6; 10.3 1.5; NR2.7; NR 6.8; NR NR; NR2.1; 12.2 2.7; NR 8.1; NR

NR, not reached.

Conclusions

M7824 had promising efficacy, with encouraging PFS and OS, and ORRs at the RP2D of 1200 mg of 40.7% and 71.4% in PD-L1+ and PD-L1 high pts, respectively. Treatment was well tolerated.

Clinical trial identification

NCT02517398.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Editorial Acknowledgement

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

Disclosure

E. Felip: Employment: Vall d'Hebron University Hospital; Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardan Health, Merck Sharp & Dohme Corp, Novartis, Pfizer, Roche, Takeda, Abbvie, Merck; Speakers' bureau: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardan Health, Merck Sharp & Dohme Corp, Novartis, Pfizer, Roche, Takeda, Abbvie, Merck. I. Dussault, L. Ojalvo: Employment: EMD Serono. C. Helwig: Employment and Equity Ownership: Merck KGaA. All other authors have declared no conflicts of interest.

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