Skip to main content

Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

A Phase I, open-label, dose escalation study of MGA271 in combination with pembrolizumab in patients with B7-H3-expressing melanoma, squamous cell cancer of the head and neck, or squamous cell non-small cell lung cancer

Background

MGA271 is an Fc optimized humanized IgG1 monoclonal antibody that binds to B7-H3 (CD276), a member of the B7 family, currently undergoing Phase I testing. The Fc domain is engineered for enhanced binding to the activating FcγR, CD16A, and decreased binding to the inhibitory FcγR, CD32B. B7-H3 has limited expression in normal tissue and high expression in multiple tumors including melanoma (M), squamous cell cancer of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). The correlation between B7-H3 overexpression and poor prognosis in certain cancers suggests a role for B7-H3 in tumor escape. Despite the clinical success of agents including anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies, the majority of patients with M, SCCHN or NSCLC progress nonetheless, and substantial unmet need exists for these patients. The underlying hypotheses for combining MGA-271 (anti-B7-H3) with pembrolizumab (anti-PD-1) are: 1) combining immune-modulating agents may mediate additive or synergistic antitumor activity (e.g. anti-CTLA-4+anti-PD-1), and can do so where neither single agent has pronounced antitumor activity (e.g. anti-PD-1+anti-LAG-3), 2) coordinate engagement of both innate and adaptive immunity, 3) both agents may enhance the immune response against tumors via modulation of T cell immunosuppression, and 4) limited expression of B7-H3 on normal tissues may help focus an immune attack on tumors, limiting the risk of immune-related adverse events (irAEs) resulting from the disruption of self-tolerance, allowing MGA271 to be combined more readily with other immune-modulating agents, including anti-CTLA-4 and anti-PD-1 antibodies. /PD-1 /PD-L1.

Methods

This US, multi-center, open-label trial (NCT02475213) enrolls patients with advanced B7-H3-expressing SCCHN, M, or squamous NSCLC. Progression on previous checkpoint inhibitor is allowed. Following a 3+3 +3 dose escalation scheme, successive cohorts of patients will receive escalating doses of weekly IV MGA271 beginning at 3 mg/kg, and a fixed dose of IV pembrolizumab (2 mg/kg) administered every three weeks. Both study drugs will be administered starting on Day 1 of the study and given for up to one year. A three-cohort expansion phase will open at the established MTD with 16 patients each with M, SCCHN and NSCLC. The primary objective of this study is to determine the safety, dose-limiting toxicity and maximum tolerated dose of the MGA271/pembrolizumab combination. Secondary objectives include evaluation of pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of this combination. This novel study will provide the first clinical assessment of coordinated targeting of both the B7-H3 and PD-1/PD-L1 axes in patients with advanced cancer.

Trial registration

ClinicalTrials.gov identifier NCT02475213.

Author information

Affiliations

Authors

Corresponding author

Correspondence to James Vasselli.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Baughman, J., Loo, D., Chen, F. et al. A Phase I, open-label, dose escalation study of MGA271 in combination with pembrolizumab in patients with B7-H3-expressing melanoma, squamous cell cancer of the head and neck, or squamous cell non-small cell lung cancer. j. immunotherapy cancer 3, P177 (2015). https://doi.org/10.1186/2051-1426-3-S2-P177

Download citation

Keywords

  • Melanoma
  • Dose Escalation
  • Squamous Cell Cancer
  • Checkpoint Inhibitor
  • IgG1 Monoclonal Antibody