146P - Tolerability and pharmacokinetics (PK) of ABT-414 in Japanese patients (pts) with recurrent malignant glioma

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Pharmacology
Central Nervous System Malignancies
Presenter Yoshitaka Narita
Citation Annals of Oncology (2016) 27 (suppl_9): ix42-ix45. 10.1093/annonc/mdw578
Authors Y. Narita1, M. Nagane2, N. Kagawa3, K. Mishima4, T. Yamamoto5, T. Wakabayashi6, T. Hamada7, R. Odagawa7, Y. Nishimura7, T. Kiriyama7, H. Xiong8, C. Ocampo9, R. Nishikawa4
  • 1Neurosurgery And Neuro-oncology, National Cancer Center Hospital, 104-004 - Tokyo/JP
  • 2Department Of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo/JP
  • 3Neurosurgery, Osaka University Hospital, 565-0871 - Osaka/JP
  • 4Department Of Neuro-oncology/neurosurgery, Saitama International Medical Center, 350-1298 - Saitama-ken/JP
  • 5Neurosurgery, University of Tsukuba Hospital, 305-8576 - Ibaraki/JP
  • 6Neurosurgery, Nagoya University Hospital, 466-8560 - Aichi/JP
  • 7Development, AbbVie GK, 108-6302 - Tokyo/JP
  • 8R4pk, AbbVie, 60064 - North Chicago/US
  • 9R48k, AbbVie, 60064 - North Chicago/US

Abstract

Background

Pts with glioblastoma (GBM; WHO grade IV) have a poor prognosis. Epidermal growth factor receptor amplification (EGFR amp) is present in ∼50% of GBM, resulting in a unique protein conformation of EGFR that can be targeted by an antibody-drug conjugate, ABT-414. ABT-414 is comprised of an antibody, ABT-806, which targets EGFR amp, and a toxin, monomethyl auristatin F (MMAF). ABT-414 is internalized by tumor cells and MMAF is released, resulting in cell death. Here we report tolerability and PK of ABT-414 alone and with radiation therapy (RT) and temozolomide (TMZ) in Japanese pts.

Methods

Study M13-714 (NCT02590263) is a non-randomized, open-label, Phase 1/2 study in Japanese pts. Phase 1, Arm A evaluates tolerability and PK of ABT-414 only in WHO grade III-IV recurrent glioma (rGBM); Arm B evaluates ABT-414 + RT/TMZ in newly diagnosed pts. Phase 2 assesses efficacy of ABT-414 + TMZ in EGFR amp, rGBM. Presented here are Phase 1, Arm A results (3 + 3 dose escalation; 0.5-1.25 mg/kg, i.v. every 2 weeks), and preliminary Phase 1, Arm B results.

Results

As of June 13, 2016, 10 pts were enrolled. Arm A, n = 9 pts at 3 doses: 0.5 mg/kg (n = 3); 1.0 mg/kg (n = 3); 1.25 mg/kg (n = 3). Arm B, n = 1 pt at 1.0 mg/kg + RT/TMZ. In Arm A, 6 pts were screened for EGFR amp; 2/6 (33%) were positive. The most common treatment emergent adverse events (TEAEs, ≥1 pt) were ocular-related, keratopathy (4/10, 40%) as most prevalent. Other TEAEs were increased ALT/AST levels (4/10, 40% each) and decreased platelet count and corneal injury (2/10, 20% each). The most common Grade 3/4 TEAEs were corneal erosion, keratitis, decreased platelets and malignant neoplasm progression (1 pt, 10% each). Four pts had stable disease (SD), with 1 pt (EGFR+) maintaining SD for 40 weeks. Preliminary PK analysis for ABT-414 and ABT-806 was done on 7 pts (0.5 mg/kg, n = 2; 1.0 mg/kg, n = 3; 1.25 mg/kg, n = 2), and for cys-mcMMAF on 5 pts (0.5 mg/kg, n = 2; 1.0 mg/kg, n = 3). Cmax (maximum serum concentration) and AUC14day (area under the curve, drug concentration vs time) were approximately dose-proportional for ABT-414 and cys-mcMMAF.

Conclusions

ABT-414 displayed acceptable tolerability and PK profile in Japanese pts, suggesting that it may be a novel therapy for those in need of better treatments.

Clinical trial indentification

NCT02590263

Legal entity responsible for the study

AbbVie, Inc.

Funding

AbbVie, Inc.

Disclosure

Y. Narita: Honoraria (lecture fees) from Chugai Pharmaceutical Co., MSD; research funding from Nihon Medi-Physics Co. and AbbVie GK. M. Nagane: Honoraria: Chugai, MSD KK, Eisai, Otsuka, Novartis, Ono, Bayer Schering, Nobelpharma, AbbVie, Novocure. Research funding: Daiichi Sankyo, Chugai, MSD KK, Eisai, Kyowa Hakko Kirin, AbbVie, Ono, Mitsubishi Tanabe, Pfizer. Gifts: Daiichi-Sankyo, AbbVie GK. T. Wakabayashi: Contributions from Pfizer. T. Hamada, R. Odagawa, Y. Nishimura, T. Kiriyama, H. Xiong, C. Ocampo: Employee of AbbVie and may own stock. R. Nishikawa: Honoraria from Chugai Pharmaceutical Co., MSD, Eisai, Novocure and AbbVie. All other authors have declared no conflicts of interest.