3601 - Safety and clinical activity of MEDI0562, a humanized OX40 agonist monoclonal antibody, in adult patients with advanced solid tumors

Background

MEDI0562, a humanized IgG4 OX40 monoclonal antibody, demonstrated a manageable safety profile and pharmacologic activity in preliminary analyses of the Phase 1 study (NCT02318394) in pts with advanced solid tumors.¹ Here we present updated safety data and clinical activity for pts treated during the dose-escalation phase.

Methods

Pts were treated with one of 6 escalating doses of MEDI0562 (0.03, 0.1, 0.3, 1.0, 3.0, and 10 mg/kg) every 2 weeks (Q2W) until confirmed disease progression or unacceptable toxicity. Tumor assessments were performed every 8 weeks with immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).

Results

A total of 55 pts received MEDI0562 across 6 dose cohorts (3 + 3 design), with a maximum administered dose of 10 mg/kg Q2W and no DLTs observed. Median duration of exposure was 10 (2 to 48) weeks. Adverse events (AEs) and treatment-related AEs (trAEs) were reported in 96% and 67% of pts, respectively; the most common trAEs were fatigue (31%) and infusion-related reaction (15%). Gr 3 trAEs occurred in 16% of pts with the most common being pyrexia (4%); 53% of pts had trAEs of Gr1 or 2, with no apparent dose relation. There were no trAEs leading to discontinuation or Gr 4 or 5 trAEs. Of 50 response evaluable pts, 2 pts (sq cell carcinoma of the larynx – 0.03 mg/kg Q2W and bladder cancer – 3 mg/kg Q2W) had irPR at the first tumor assessment, with an overall survival of 13.8 and 10.2+ mos, respectively. Stable disease was seen in 22 (44%) pts with SD in 20 pts lasting >3 mos. Serum exposure of MEDI0562 increased approximately dose proportionally. Posttreatment antidrug antibody (ADA) was detected in 26 (51%) of 55 pts. ADA exhibited variable impact on PK exposure at all doses below 3 mg/kg. A 1.5 to 3.0-fold increase in mean peaks of the percentage of peripheral Ki67+ CD4+ and Ki67+ CD8 +memory T cells was observed across ascending dose levels.

Conclusions

MEDI0562 was generally well tolerated in adult pts with advanced solid tumors and exhibited clinical and pharmacological activity. Based on the ADA data, a suggested MEDI0562 Phase 2 dose of ≥ 3 mg/kg Q2W was selected. 1. Glisson et al Ann Oncol ESMO 2016.

Clinical trial identification

NCT02318394.

Legal entity responsible for the study

MedImmune.

Funding

MedImmune, the global biologics R&D arm of AstraZeneca.

Editorial Acknowledgement

Disclosure

B. Glisson: Research funding to institution: Pfizer, Inc. R. Leidner: Institutional research funding: MedImmune, BMS, and Ignyta; Honoraria: AstraZeneca; Advisory board: Regeneron and Merck. R.L. Ferris: Advisory board: Amgen, AstraZeneca/MedImmune, Bristol-Myers Squibb, EMD Serono, PPD, Lilly, Merck, Pfizer, Tesaro; Clinical trial research funding: AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck; Research funding: Tesaro, VentiRx Pharmaceuticals. J. Powderly: Clinical trial funding: AstraZeneca, Curis, Corvus, InCyte, AbbVie, BMS, MacroGenics, Top Alliance BioSciences. N.A. Rizvi: Consulting/Advisory board: AstraZeneca, Abbvie, BMS, Eli Lilly, Merck, Merck KGaA, Novartis, Pfizer, Regeneron, Roche; Board of directors member and shareholder: ARMO BioSciences; Co-founder and shareholder: Gritstone Oncology; Scientific advisory board member: Neogenomics. Y. Zheng, S. Eck, D.M. Townsley: Employee: MedImmune, AstraZeneca. S.P. Patel: Consulting, institutional research support: AstraZeneca/MedImmune. All other authors have declared no conflicts of interest.