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Phase 1 study of MEDI0562, a humanized OX40 agonist monoclonal antibody (mAb), in adult patients (pts) with advanced solid tumors

Date

10 Oct 2016

Session

Immunotherapy of cancer

Presenters

Bonnie Glisson

Citation

Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378

Authors

B.S. Glisson1, R. Leidner2, R.L. Ferris3, J. Powderly4, N. Rizvi5, J.D. Norton6, J. Burton7, M.C. Lanasa6, S.P. Patel8

Author affiliations

  • 1 Thoracic/head And Neck Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 2 Medical Oncology; Hematology, Providence Cancer Center Oncology and Hematology Care Clinic Eastside Portland, 97213 - Portland/US
  • 3 Division Of Head And Neck Surgery Departments Of Otolaryngology, University of Pittsburgh, Eye and Ear Institute, 15213 - Pittsburgh/US
  • 4 Carolina Biooncology Institute Llc, Carolina BioOncology Institute LLC, 28078 - Huntersville/US
  • 5 Hematology And Oncology, Columbia Medical Center College of physicians & surgeons, 10032 - New York/US
  • 6 Oncology, MedImmune LLC, 20878 - Gaithersburg/US
  • 7 Oncology, MedImmune Ltd, CB21 6GH - Cambridge/GB
  • 8 Experimental Therapeutics, Thoracic Oncology, UC San Diego Moores Cancer Center, 92093 - La Jolla/US
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Background

In preclinical studies, OX40 agonists have been shown to stimulate immune effector and memory T cell function while attenuating immunosuppressive function of regulatory T cells, leading to anti-tumor activity.

Methods

This is a Phase 1 study evaluating MEDI0562, a humanized OX40 agonist mAb, in adult pts with advanced solid tumors. The study has 2 phases: dose escalation and dose expansion. Dose escalation follows 3 + 3 design with pts enrolled in sequential cohorts of up to 6 dose levels of MEDI0562 (0.03, 0.1, 0.3, 1.0, 3.0, or 10 mg/kg, via intravenous infusion). Tumor assessments are performed every 8 weeks. Selected pts have mandatory pre- and on-treatment tumor biopsies to explore the relationship between drug exposure and pharmacodynamics. We report the preliminary results of safety, tumor response, pharmacokinetics, and pharmacodynamics in the dose escalation phase.

Results

As of April 01 2016, 27 pts were treated (n = 7, 9, 7, 4 received 0.03, 0.1, 0.3, and 1 mg/kg MEDI0562, respectively). Adverse events (AEs) and treatment-related AEs were seen in 24 (88.9%) and 16 (59.3%) pts, respectively; the only related AE occurring in ≥ 10% of pts was fatigue (8/27, 29.6%). Most pts experienced AEs of Grade 1 and 2 in severity. Serious AEs (SAEs) were seen in 12 (44.4%) pts; no treatment-related or immune-related SAEs were observed. No related treatment discontinuations, deaths or dose limiting toxicities have occurred. Of 19 evaluable pts, 1 pt (0.03 mg/kg) with squamous cell carcinoma of the larynx had partial response at first tumor assessment and maintained for 3.7+ months (ongoing); 4 pts had stable disease. Serum exposure of MEDI0562 increased approximately dose proportionally. A 2-3-fold mean increase in peripheral Ki67+ CD4+ memory T cells was observed. Paired tumor biopsies showed induction of PD-L1 expression and increased CD8+ T cell infiltration in 2 of 3 evaluated pts, including 1 pt at 0.03 mg/kg. Updated clinical data will be presented at the meeting.

Conclusions

Preliminary data showed that MEDI0562 is generally well tolerated in adult pts with advanced solid tumors and exhibits clinical and pharmacological activity. A maximum tolerated dose has not been determined.

Clinical trial identification

NCT02318394

Legal entity responsible for the study

MedImmune LLC

Funding

MedImmune LLC

Disclosure

B.S. Glisson: Research funding for Clinical Trials from Pfizer, Bristol Myers Squibb, Oncomed, Stemcentrx, and Medimmune provided for MD Anderson. I am a PI on these grants. R. Leidner: Research is being supported by: Medimmune/ Astra Zeneca and Bristol-Myers Squibb R.L. Ferris: Paid member of Advisory Board (Ad-Hoc)- Merck, Celgene, Bristol Myers Squibb, AZ/Medimmune Research/Grant Funding- VentiRx, Bristol Myers Squibb AZ/Medimmune. J. Powderly: Lion BioTechnologies, Juno Therapeutics, BlueBird Bio, Kite Pharma, ZioPharm Oncology, BMS, Genentech, EMD, Serono, AstraZeneca, InCyte, Macrogenics, Sequenom, Corvus, Carolina BioOncology Institute, PLLC, BioCytics Inc., Human Applications Lab, Merck. N. Rizvi: Consulting for AstraZeneca, Merck, Roche, Novartis, Lilly. Co-founder and shareholder, Gritstone Oncology. J.D. Norton: I am an employee of MedImmune LLC, a subsidiary of AstraZeneca, and hold restricted AstraZeneca stock shares. J. Burton: Employee of MedImmune Ltd. M.C. Lanasa: Employee of MedImmune LLC / AstraZeneca. S.P. Patel: Dr. Patel receives research funding from: MedImmune, Genentech, Pfizer, Amgen, Xcovery, Lilly, Bristol-Myers Squibb. He receives consulting fees from: Lilly, Pfizer. He receives speaking fees from: Boehringer Ingelheim, Merck.

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