47TiP - TACTI-mel (Two ACTive Immunotherapeutics in melanoma): A Phase 1 trial in patients with unresectable or metastatic melanoma receiving IMP321 (LAG-3...

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Christian Mueller
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors C. Mueller1, F. Triebel2
  • 1Clinical Development, Prima Biomed, 04103 - Leipzig/DE
  • 2Medical Sciences, Immutep S.A.S., 91893 - Orsay/FR

Abstract

Aim/Background

This ongoing Phase I clinical trial aims to investigate the safety, tolerability and recommended phase 2 dose (RPTD) of IMP321 when combined with anti-PD-1 treatment in patients with unresectable or metastatic melanoma. The study will also evaluate the combined effects on patients' immune responses. IMP321 consists of the extracellular portion of the human lymphocyte activation gene 3 (LAG-3) protein fused to the Fc fraction of a human IgG1. This soluble LAG-3Ig fusion protein, like the membrane form of LAG-3 naturally expressed on human T cells, binds to major histocompatibility complex (MHC) class II molecules on the surface of antigen presenting cells (APC) and leads to their activation with enhanced presentation of tumour antigens to T cells. As a result, IMP321 may help to better activate the cellular immune response mechanisms known to mediate tumour recognition and killing.

Trial design

This is a multicentre, open-label, dose escalation Phase I clinical trial (N = 24) of IMP321 in combination with pembrolizumab. Patients who achieved asymptomatic immune-related progressive disease or sub-optimal response after 3 cycles of pembrolizumab will begin IMP321 therapy starting at cycle 5 of pembrolizumab. In three staged and sequential dose escalation cohorts, doses of 1, 6, or 30 mg IMP321 will be administered every 2 weeks throughout cycles 5 to 13 of pembrolizumab. After completion of combined treatment responding or stable patients may continue receiving pembrolizumab according to local clinical practice. Patients will be evaluated for dose limiting toxicities (DLTs) according to the current National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE v4.03). Tumour response will be radiologically assessed according to immune related response criteria (irRC) and response evaluation criteria in solid tumours (RECIST) version 1.1 until progressive disease, unacceptable toxicity, death, or until the end of the study if a patient does not progress or die during the study.

Clinical trial identification

The TACTI-mel trial protocol has been released on 16 ctober 2015. The trial identifiers are IMP321-P012 (sponsor code) and NCT02676869 (ClinicalTrials.gov)

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Legal entity responsible for the study: Prima Biomed Ltd

Funding

Prima Biomed Ltd

Disclosure

C. Mueller: Employed at a 100% affiliate of Prima Biomed Ltd. F. Triebel: CMO and CSO of Prima Biomed Ltd.