Volume 2 Supplement 3

Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

Open Access

Development of MEDI4736, an anti-programmed cell death ligand 1 (PD-L1) antibody, as monotherapy or in combination with other therapies in the treatment of non-small cell lung cancer (NSCLC)

  • Julie Brahmer1,
  • Ani Balmanoukian2,
  • Sarah Goldberg3,
  • Sai-Hong Ou4,
  • Andrew Blake-Haskins5,
  • Joyson Karakunnel5,
  • Paul Stockman6,
  • Naiyer Rizvi7 and
  • Scott Antonia8
Journal for ImmunoTherapy of Cancer20142(Suppl 3):P179

DOI: 10.1186/2051-1426-2-S3-P179

Published: 6 November 2014

Background

MEDI4736 is an engineered human IgG1 that blocks PD-L1 binding to PD-1 and allows T-cells to recognize and kill tumor. MEDI4736 has single-agent activity and potential for further increased activity in combination. A comprehensive development programme is underway in NSCLC, as monotherapy and in combination.

Methods

NSCLC data from 2 multicentre, open-label Phase I studies are reported. NCT01693562 evaluates safety and efficacy of MEDI4736 administered every 2 or 3 weeks. NCT02000947 evaluates safety and efficacy of MEDI4736 in combination with tremelimumab, a human IgG2 anti-CTLA-4 mAb, at 4-week intervals.

Results

NCT01693562: As of May 2014, NSCLC cohort included 155 patients (pts) (median age 65 years [33-85], PS 0/1/unknown [25%/73%/2%], median 3 [0-7] prior treatments). Median follow-up: 6 weeks (range 0-67). Treatment-related adverse events (TRAEs): 29% (Grade [Gr] ≥3: 3%); none led to treatment discontinuation. Most frequent TRAEs: fatigue (7%), nausea (5%), and vomiting (5%). No treatment-related colitis any Gr. No treatment-related Gr 3/4 pneumonitis or dyspnea. 58 pts had ≥12 weeks follow-up: 16% had partial response (as early as 6 weeks), duration of response ranged 5-54+ weeks, disease control rate 35%. PD-L1 positivity appears to enrich for response.

NCT02000947: As of April, 2014, 12 pts treated at 4 dose-levels (PS 0-1, median 3 [2-5] prior treatments). No DLTs observed in any cohort during DLT observation period. Most frequent TRAEs: -↑amylase, abdominal pain, arthralgia, colitis, diarrhea, epigastric discomfort, fatigue and nausea. TRAEs ≥Gr 3 noted in 3 pts: Gr 3 - ↑AST/ALT & Gr 5 myasthenia (MG) (n = 1), Gr 3 diarrhea/colitis (n = 1), Gr 4 - ↑amylase (n = 1). TRAEs led to discontinuation in two subjects: Gr 5 MG and Gr3 colitis. In 12 response-evaluable pts (Figure 1), tumor shrinkage at 8 weeks: 0/3 pts cohort 1a; 6/9 pts cohorts 2a and 3a/b; disease control: 7/12 pts. Dose-escalation ongoing; total of 6 dose-levels, including cohort 5a (MEDI4736/Treme: 15/10 mg/kg), has been cleared since cut-off.
Figure 1

Red: Cohort1a (MEDI4735/Treme: 3/1); Green: Cohort 2a (MEDI4736/Treme 10/1); Gold: Cohort 3a (MEDI4736/Treme 15/1); Blue: Cohort 3b (MEDI4736/Treme 10/3).

Conclusions

Current safety profile and encouraging early antitumor activity (monotherapy and combination) support continued development in NSCLC. Additional monotherapy NSCLC studies: Phase II 'ATLANTIC' (NCT02087423), Phase III 'PACIFIC' following chemo-radiotherapy (NCT02125461), Combination: Phase I + gefitinib (NCT02088112), and Phase Ib + AZD9291 (NCT02143466). Monotherapy and combination: Phase III 'ARCTIC' vs standard-of-care.

Declarations

Acknowledgements

Writing support-Isobel Lever/Ashfield Communications, funding-AstraZeneca

Trial registration NIH

Authors’ Affiliations

(1)
Sidney Kimmel Comprehensive Cancer Center at John Hopkins University
(2)
The Angeles Clinic and Research Institute
(3)
Yale University, Yale Cancer Center
(4)
Chao Family Comprehensive Cancer Center
(5)
MedImmune
(6)
AstraZeneca Pharmaceuticals
(7)
Memorial-Sloan Kettering Cancer Center
(8)
H. Lee Moffit Cancer Center and Research Institute

Copyright

© Brahmer et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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