First-In-Man Clinical Trial of IMP321 to Treat Melanoma Looks Promising
Australian Biotech Company, Prima BioMed announced the results of the combination therapy clinical trial program for the treatment of unresectable or metastatic melanoma patients.
The trial is the first-in-man Phase I study of IMP321 in combination with Merck’s Keytruda® (pembrolizumab), a PD-1 checkpoint inhibitor. The trial was conducted in unresectable or metastatic melanoma patients with very insignificant or no response to the anti PD-1 therapy. The patients were administered combination therapy of the lead candidate with Keytruda in order to enhance their immune responses and increase the tumor response rate to Keytruda.
The lead candidate IMP321 is a soluble LAG-3 Ig fusion protein, first-in-class Antigen Presenting Cell (APC) activator developed on the basis of control mechanisms of immune checkpoint LAG-3, known to play an important function in the regulation of the T cell immune response. This candidate is the first of its kind active immunotherapy drugs in which the individual’s own immune system is leveraged to respond to the antigenic debris of tumor formed by chemotherapy. IMP321 can produce better anti-tumor CD8 T cell response by enhancing the dendritic cells network and responding to tumor antigens.
The clinical trial program named TACTI-mel (Two ACTive Immunotherapeutics in melanoma) is being conducted to evaluate the company’s lead candidate IMP321 in unresectable or metastatic melanoma patients. The Data Safety Monitoring Board (DSMB) from the Interim results of the first dose level study confirmed the drug to be safe and well tolerated when used as a combination therapy with PD-1 blocking antibody. Furthermore, the interim results confirmed that the dose escalation study of IMP321 will continue as previously planned.
No serious adverse events related to the therapy were reported and the DSMB green-lighted the continuation of the dose escalation program. Now the study will move ahead with 6 mg dose level. Updates of the data on the basis of safety and efficacy are expected to be published in 2017.
Prima’s Chief Medical Officer, Dr. Frédéric Triebel, said: “The majority of metastatic melanoma patients do not respond well to Keytruda, a key reason being that their tumors are poorly infiltrated by activated T cells expressing PD-1. By introducing IMP321, a first-in-class Antigen Presenting Cell (APC) activator, these patients may now be able to repopulate their tumor with more activated T cells which are responsive to KEYTRUDA. So, by combining the effect of ‘pushing the gas’ with IMP321 and ‘releasing the brake’ with KEYTRUDA we propose a rational therapeutic approach to increase the response rate by further boosting anti-tumor CD8 T cells”.
In a Phase II clinical study (AIPAC) IMP321 is being studied as a chemoimmunotherapy candidate for metastatic breast cancer treatment. Additionally, the biotech along with other large pharmaceutical partners is developing few LAG3 based products such as LAG-3 products including antibodies for modulation of immune response in autoimmunity and cancer.
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