Novel Immunotherapy Tebentafusp Granted Fast Track Designation for Metastatic Uveal Melanoma

The FDA has granted tebentafusp (IMCgp100) a fast track designation for the treatment of patients with HLA-A*0201-positive previously untreated metastatic uveal melanoma, according to Immunocore Limited, the company developing the novel immunotherapy agent.

In findings from a phase I study, tebentafusp demonstrated an overall survival (OS) rate of 74% at 1 year in patients with heavily pretreated metastatic uveal melanoma. At a median follow-up of 15.9 months, the median OS had not yet been reached.

Sixty-six percent of patients (95% CI, 39%-83%) remained alive and progression-free at 1 year by immune-related response criteria.

The objective response rate was 11% (90% CI, 2%-30%) with IMCgp100, with 4 additional patients showing signs of stable disease with minor responses (≥10% reduction in target lesions). The median duration of response was 30.6 weeks.

The Fast Track program from the FDA facilitates the accelerated development and review of drugs that are designed to treat serious conditions that may fill a current unmet medical need. The T-cell receptor—based therapy was previously granted an orphan drug designation by the FDA for melanoma and was granted a Promising Innovative Medicine Designation under the UK Early Access to Medicines Scheme.

“For patients with metastatic uveal melanoma, the prognosis is poor and has not meaningfully changed in decades. Our goal is to test whether tebentafusp can prolong survival for these patients,” said David Berman, head of research and development at Immunocore, in a statement. “We are delighted that tebentafusp has been granted fast track designation.”

Nineteen patients were included in the phase I dose-escalation portion of the study. On day 1 of the first cycle, patients received IMCgp100 at 20 μg, which was escalated to 30 μg on day 2 of cycle 2, followed by enrollment to 1 of 4 cohorts testing a range of doses (54 μg, 64 μg, 73 μg, and 68 μg).

The median age of patients was 55 years, and the ECOG performance scores were 0 (74%) and 1 (26%). Patients had received a median of 4 prior therapies (range, 0-8), which included chemotherapy for 95% of patients and prior immunotherapy for 68%. Prior immunotherapy included ipilimumab (Yervoy; 47%), pembrolizumab (Keytruda; 32%), and nivolumab (Opdivo; 16%). All patients had liver metastases, and LDH levels were greater than the upper limit of normal for 73% of patients.

Dose-limiting toxicities of abnormal liver function tests (grade 3/4 ALT or AST changes) were seen in 3 patients, but all of the toxicities were reversible. Two of these events were seen in the 4 patients who received the highest dose, which was subsequently reduced to 68 μg. This dose was identified as the maximum tolerated dose of IMCgp100 and will be further explored in phase II trials.

The pivotal phase II IMCgp100-102 trial (NCT03070392) is currently ongoing. The study is randomizing HLA-A*0201-positive adult patients with previously untreated metastatic uveal melanoma 2:1 to either tebentafusp or investigator’s choice of dacarbazine, ipilimumab, or pembrolizumab. Eligible patients are those with advanced disease who have not received prior systemic or liver-directed chemotherapy, radiotherapy, or immunotherapy in the advanced or metastatic setting. The primary endpoint is OS and secondary endpoints include objective response rate, duration of response, progression-free survival, disease control rate, quality of life, safety, and pharmacokinetics.

Reference:

Immunocore. Immunocore's Lead Asset Tebentafusp Gains Fast Track Designation for Metastatic Uveal Melanoma. Published April 3, 2019. https://bit.ly/2UUPKNU. Accessed April 8, 2019.