Rare Disease Report

Dr Takami Sato Discusses IMCgp100 Treatment for Metastatic Uveal Melanoma

JUNE 26, 2018
Krista Rossi
In a recent interview with Rare Disease Report®, Takami Sato, MD, PhD, from the department of Medical Oncology at Kimmel Cancer Center, Thomas Jefferson University, discussed the use of IMCgp100 as a treatment for metastatic uveal melanoma (mUM).

Dr Sato was the lead investigator of a phase 1/2 study which evaluated the safety and preliminary efficacy of IMCgp100 in mUM patients; the findings were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

IMCgp100 is a bispecific biologic comprised of a soluble T-cell receptor recognizing the gp100 antigen fused to a scFV anti-CD3 that redirects T-cell lysis of melanoma cells expressing gp100, in mUM.

In the interview, Dr Sato provided a little bit of background on mUM and its low response rates to treatment. “Metastatic uveal melanoma is a very rare form of melanoma, but it is the most common cancer in the eye; it is primarily an eye tumor,” he explained. “This is quite different from skin melanoma, which shows a significant response rate. Metastatic uveal melanoma has very low response rates. The potent response with ipilimumab is 5%, and the potent anti-PD-1 antibody is 3.6 %.”
 
Among HLA-A*0201+ classified mUM patients included in the study, 19 subjects were administered once-weekly (QW) dosing of IMCgp100 iv at cycle 1, day 1 (C1D1, 20 mcg) and C1D8 (30 mcg), followed by the escalated dose administered at C1D15 and beyond. Due to edema and hypertension side effects, appropriate doses were also investigated, according to Dr Sato.

“This is a very interesting new fusion molecule combining T-cell receptors, synchronizing the protein, gp100, fused to the antibody CG3,” Dr Sato said. “These T-cell receptors recognize melanopsin, the agent protein, which is mutated to increase the binding chemistry for mobility. Once we infuse this medicine, it goes onto the pigmented cell.”

IMCgp100 was found to be tolerable with the intra-patient escalation dosing regimen and correlative with prolonged overall survival (OS). However, a potential association of prolonged OS with rash severity was observed, according to the study abstract. Furthermore, a relationship between lymphocyte trafficking and exposure to IMCgp100 was demonstrated by pharmacokinetic/pharmacodynamic (PKPD) modeling.

“The most important point we presented at ASCO was that the majority of patients stayed alive,” he said. “This treatment is well tolerated compared with checkpoint blockades like the nivolumab and ipilimumab combination, which is very toxic. The survival is very different from traditional methods; that’s the key point.”   

Looking forward, pivotal mUM trials, including expansion trials, continue to enroll subjects in the hope of further defining the capability of the treatment and its effects.

“There are 2 current ongoing studies” Dr Sato shared. “I’m hoping in 1 to 2 years, the government will grant a temporary approval for this treatment because there really is nothing for this disease.”

In addition, Dr Sato highlighted the possibility of using the IMCgp100 treatment as a preventative measure to inhibit grim outcomes before they occur. “Once the medicine is approved, we can do many things. We can start talking about prevention. Patients at high risk could possibly receive this medicine as a prevention,” he explained. “These [mUM] patients have high risks for mortality; there is a 50% to 70% death rate. Therefore, if this medicine is available for patients who have high risk, we can potentially decrease the number of patients who die from this disease with prevention.”  

The estimated primary completion date for the phase 1/2 study is September 2019.

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