986O - Randomized phase II study of MEHD7945A (MEHD) vs cetuximab (Cet) in >= 2nd-line recurrent/metastatic squamous cell Carcinoma of the head & neck (RM...

Date 27 September 2014
Event ESMO 2014
Session Head and neck cancer
Topics Anticancer agents
Head and Neck Cancers
Therapy
Biological Therapy
Presenter Jérôme Fayette
Citation Annals of Oncology (2014) 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340
Authors J. Fayette1, L.J. Wirth2, C. Oprean3, R. Hitt4, A. Udrea5, A. Jimeno6, D. Rischin7, C. Nutting8, P.M. Harari9, T. Csőszi10, D. Cernea11, X. Wang12, A. Kapp12, M. Anderson12, E. Penuel12, B. McCall13, A. Pirzkall14, J.B. Vermorken15
  • 1Medical Oncology, Centre Léon Bérard, 69008 - LYON/FR
  • 2Medicine, Massachusetts General Hospital, 02114 - Boston/US
  • 3Medical Oncology, Oncomed Timisoara, RO-300239 - Timisoara/RO
  • 4Oncology, Centro Integral Oncologico Clara Campal, Madrid/ES
  • 5Oncology, Medisprof SRL, Cluj-Napoca/RO
  • 6Medicine/oncology And Otolaryngology, University of Colorado School of Medicine, 80045 - Aurora/US
  • 7Oncology, Peter MacCallum Cancer Center, East Melbourne/AU
  • 8Clinical Oncology, Royal Marsden NHS Trust, London/GB
  • 9Human Oncology, University of Wisconsin Hospital and Clinics, Madison/US
  • 10Onkologiai Kozpont, Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rend.Int., Szolnok/HU
  • 11Oncology, Institutul Oncologic Prof. Dr. Ion Chiricuta, Cluj-Napoca/RO
  • 12Research And Early Development, Genentech, Inc., South San Francisco/US
  • 13Product Development, Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 14Oncology Early Clinical Development, Genentech, Inc., South San Francisco/US
  • 15Department Of Oncology, U.Z.A. University Hospital Antwerp, 2650 - Edegem/BE

Abstract

Aim

MEHD, a novel dual-action humanized IgG1 antibody that blocks ligand binding to EGFR and HER3, inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody dependent cell mediated cytotoxicity. MEHD is active in multiple tumor models, including models resistant to anti-EGFR or anti-HER3. Preclinical and early clinical data suggest that high expression of neuregulin 1 (NRG1) in tumors may enhance sensitivity to MEHD.

Methods

This multicenter, open-label, randomized phase II study evaluated efficacy in RMSCCHN patients (pts) progressive on/after PtCT, and in those whose tumors express high NRG1. Primary endpoint = PFS (RECIST v1.1), secondary endpoints = ORR, DOR, OS and safety (CTCAE v4.0). Pts received MEHD (1100 mg IV, q2w) or Cet (400 mg/m2 load, 250 mg/m2 IV, q1w) until progression or intolerable toxicity. Upon central confirmation of progression on Cet, pts could cross over to MEHD. Mandatory tumor samples are assayed for biomarkers related to mechanism of action and SCCHN, including NRG1 expression and HPV status by qRT-PCR.

Results

121 pts were randomized (59 MEHD, 62 Cet; median age 62 y, ECOG 0-2). As of 28Mar14, 8 pts remain active. Efficacy results are shown (Table) with no difference btw treatment arms. Grade ≥3 adverse events (AE) that were more frequent with MEHD (61%) compared to Cet (51%) included infections (22.0 vs 11.5%) and GI disorders (13.6 vs 6.6%) contributing to higher rates of SAEs (40.7 vs 29.5%); metabolic disorders were less with MEHD (10.2 vs 14.8%). Any grade skin toxicity was lower with MEHD (45.8 vs 59.7%).

All pts MEHD (n = 59) Cet (n = 62) HR (90% CI)
Pts with PFS event 52 (88.1%) 53 (85.5%)
Median PFS, mo (90%CI) 4.1 (2.8–4.7) 4.0 (3.0–5.0) 1.15 (0.83–1.59)
Pts with OS event 38 (64.4%) 35 (56.5%)
Median OS, mo (90%CI) 7.2 (5.3–9.4) 8.5 (6.4–10.5) 1.18 (0.80–1.73)
ORR, % (90%CI) 11.9 (6.4–20.7) 14.5 (8.3–23.9)

CI = confidence interval; HR = hazard ratio.

Conclusions

MEHD did not improve outcomes of pts with RMSCCHN compared to Cet. Crossover and biomarker analyses (ongoing) will be presented.

Disclosure

A. Udrea: Consultant to Genentech/Roche; received financial compensation for lectures and travel grants; X. Wang, A. Kapp, M. Anderson, E. Penuel, B. McCall and A. Pirzkall: Genentech employee; J.B. Vermorken: Participated in Genentech advisory board. All other authors have declared no conflicts of interest.