New Collaboration Leads to Combo Experimental Therapy for Metastatic Melanoma

Pharmaceutical companies are teaming up to combine experimental therapies that may help combat metastatic cutaneous and uveal melanomas in a whole new way. The novel international collaboration may bring new combined targeted therapies to the market much sooner.

Eli Lilly and Immunocore Limited are collaborating in immunotherapy-based clinical trials to evaluate the utility of Immunocore’s lead T-cell receptor-based investigational drug IMCgp100. This agent will be combined with Lilly’s galunisertib (LY2157299) and merestinib (LY2801653) for melanoma treatment.  The investigators will explore the durability and efficacy of potential combined regimens in patients with metastatic cutaneous and uveal melanomas.

“Combining our ImmTAC, IMCgp100 with Lilly’s galunisertib and merestinib has the potential to transform the treatment of metastatic cutaneous and uveal melanoma. Immunocore is committed to the development of IMCgp100 in metastatic uveal and cutaneous melanoma where there is such great unmet medical need,” said Eliot Forster, who is chief executive officer of Immunocore, Oxford, England.

The British and American investigators are conducting two separate trials. In a phase Ib/II clinical trial, they will assess the efficacy and safety of IMCgp100 combined with galunisertib in patients with metastatic cutaneous melanoma. In a second phase Ib/II clinical trial, they will assess IMCgp100 combined with merestinib in patients with metastatic uveal melanoma. Both trials are expected to begin within the next 6 months.

IMCgp100 and galunisertib are immunotherapies for cancer treatment, designed to boost the body’s own immune system to fight cancer with complementary mechanisms of action. IMCgp100 is Immunocore’s most advanced immune mobilizing mTCR Against Cancer (ImmTAC) molecules. These molecules are a novel class of bispecific biologic drugs based on T-cell receptors (TCRs) with ultra-high affinity for intracellular and extracellular cancer targets.

Galunisertib is a small molecule inhibitor of TGF beta R1 kinase that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumor growth, suppresses the immune system, and increases the ability of tumors to metastasize. Merestinib is a small molecule multikinase inhibitor that in vitro selectively blocks signaling of MET, MST1R (RON), AXL, and MKNK1/2 pathways that potentially play a role in metastatic uveal melanoma.

On April 2015, Mark Middleton, MD, who is a Professor of Experimental Cancer Medicine at the University of Oxford in England, presented at the American Association for Cancer Research (AACR) Annual Meeting 2015 in Philadelphia, clinical trial data from the phase I/IIa study accessing IMCgp100. The study demonstrated an excellent safety profile with objective clinical responses achieved in cutaneous and ocular melanoma patients.  The agent also demonstrated clinical responses in ipilimumab (Yervoy) and pembrolizumab (Keytruda) refractory patients. 

References:

• Semedo D. (2015). Lilly and Immunocore Announce Collaboration To Evaluate Melanoma Drug. Immuno-Oncology News.