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 Anti-Cancer Agents & Biologic Therapy
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.