The American Society of Clinical Oncology recently (ASCO) issued a “rapid recommendation” to use Kimmtrak (ingredient: tebentafusp) to treat uveal melanoma.
Kimmtrak won FDA approval early this year as the first uveal melanoma treatment.
With the latest ASCO’s recommendation, Kimmtrak became the standard therapy for treatment-naïve, HLA-A*02:01-positive, metastatic uveal melanoma.
ASCO issued a quick recommendation update for systemic therapy for melanoma in the Journal of Clinical Oncology (JCO).
The society released the guideline on systemic therapy for melanoma in 2020, but it did not include uveal melanoma.
In January, the FDA authorized Kimmtrak to treat previously untreated patients with metastatic uveal melanoma.
ASCO updated the treatment guideline quickly to reflect the FDA approval.
ASO searched for new randomized trials of systemic therapy in patients with metastatic uveal melanoma covering June 2019 (the end date of the previous guideline search) to March 7, 2022. Still, it could identify only one -- the study by Nathan et al.
The study was a phase 3 trial that compared Kimmtrak with the investigator’s choice of systemic therapy (pembrolizumab, ipilimumab, or dacarbazine) in 378 previously untreated, HLA-A*02:01-positive patients with metastatic uveal melanoma.
The study results showed that the overall survival (OS), the primary endpoint, of Kimmtrak-treated patients at one year was 73 percent, versus 59 percent of the control group.
The progression-free survival (PFS) at six months was 31 percent in the Kimmtrak group vs. 19 percent in the control group.
Updated data showed that the median OS of the Kimmtrak group was 21.7 months, about half a year extended compared to 16 months of the control group. The median PFS was 3.3 months and 2.9 months, respectively.
The objective response rate (ORR) was 9 percent in the Kimmtrak group and 5 percent in the control group.
The disease control rate (complete response, partial response, or stable legion for 12 weeks or more) was 46 percent versus 27 percent.
The most common adverse events with Kimmtrak were cytokine release syndrome (89 percent), rash (83 percent), pyrexia (76 percent), and pruritus (69 percent).
Grade 3 or higher treatment-related adverse events occurred in 44 percent of patients with Kimmtrak and 17 percent with control. However, discontinuation of treatment was rare (2 percent).
ASCO noted that tebentafusp in previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma was associated with a statistically significant increase in one-year OS and six-month PFS.
“Although the frequency of grade 3 and 4 adverse events is substantial with tebentafusp, toxicity becomes more manageable with time and does not outweigh the observed benefits,” ASCO said.
Tebentafusp’s higher disease control rate, compared with the control arm, may have led to the improved OS and PFS despite the low ORR, it went on to say.
It added that researchers should carry out further studies to understand the relationship between clinical benefit and tumor response with tebentafusp or similar agents in advanced uveal melanoma.
In conclusion, ASCO said physicians should offer tebentafusp to previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma.
As ASCO cannot recommend or oppose any specific systemic therapy for patients other than addressed by this recommendation, physicians should offer or recommend enrollment in clinical trials, it said.
Kimmtrak was first developed by the U.K.-based life science company Immunocore.
It is a bispecific protein comprised of a T cell receptor fused to an anti-CD3 immune-effector function, targeting the gp100 antigen of HLA-A*02:01, a specific human leukocyte antigen (HLA).
Kimmtrak received approval in the U.S. and Europe in January and April, respectively, to treat adult patients with HLA-A*02:01-positive metastatic uveal melanoma.