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Innovative therapy Tebentafusp reduces death risk death of eye cancer by nearly half

Innovative therapy Tebentafusp reduces death risk death of eye cancer by nearly half. Due to limited treatment options, the prognosis of patients with metastatic UM has not improved significantly in the past 40 years, and more effective treatments are urgently needed.

Recently, the US FDA announced that it has awarded the innovative TCR therapy Tebentafusp (IMCgp100) the title of “Breakthrough Therapy” (BTD) for the treatment of HLA-A * 02:01 gene-positive, unresectable or metastatic uveal melanoma (mUM) in adults patient.

The award is based on positive data from a phase 3 clinical trial. The results showed that patients treated with Tebentafusp reduced the risk of death by 49%, and the one-year survival period reached 73%.

Once approved, Tebentafusp will become the first new treatment approved for the treatment of metastatic uveal melanoma in 40 years.

▌Fatal eye cancer that is not “cold” for immunotherapy

Innovative therapy Tebentafusp reduces death risk death of eye cancer by nearly half

Uveal melanoma (UM) is the most common malignant tumor in the adult eye. It originates from the melanocytes in the uveal area of the eye. In China, it is second only to infant retinoblastoma, ranking second in ocular malignant tumors. Nearly 50% of ocular melanoma patients develop uveal melanoma metastasis, and the median survival time is about 1 year.

Half of UM patients will still have metastases after systemic treatment, and the liver is the most common site of metastasis. Once UM has metastasized, even systemic treatment rarely prolongs life, and usually dies within one year, with a very high fatality rate.

In recent years, the application of immunotherapy, represented by PD-1 immune checkpoint inhibitors, has changed the survival outcome of patients with skin melanoma. However, immunotherapy is usually ineffective for patients with metastatic uveal melanoma.

At present, UM patients generally lack effective treatment methods, and the National Comprehensive Cancer Network (NCCN) “UM Guidelines” recommends clinical trials as the first choice for metastatic disease, but so far, there are very few successful cases.

Due to limited treatment options, the prognosis of patients with metastatic UM has not improved significantly in the past 40 years, and more effective treatments are urgently needed.

▌Accurately kill cancer cells: Tebentafusp

Tebentafusp is a new type of bispecific protein, which is formed by combining TCR targeting tumor antigen with immune effector domain that binds to CD3.

The TCR targeting domain binds to the human leukocyte antigen (HLA)-peptide (pHLA) complex on the cell surface, and the anti-CD3 effector domain participates in and activates CD3+ T cells. The peptide antigens provided by HLA account for about 90% of the proteome, providing a wide range of potential targets.

The drug is designed to specifically target a peptide complex with the melanoma-associated antigen gp100, which is overexpressed in melanoma cells, weakly expressed in normal melanocytes, and least expressed in other tissues.

Tebentafusp recognizes and kills tumor cells by redirecting and activating T cells.

Previously, the FDA had granted tebentafusp fast track designation and the title of “orphan drug”.

▌Clinical data is eye-catching, with a one-year survival period of 73%!

This identification is based on an ongoing Phase 3 randomized, open-label, multicenter IMCgp100-202 study (NCT03070392).

The Phase 3 clinical trial called IMCgp100-202 (NCT03070392) enrolled 378 newly-treated patients with metastatic uveal melanoma and evaluated the effects of Tebentafusp and other therapies selected by the researchers.

These therapies include Dacarbazine, anti-CTLA-4 therapy “Y drug” ipilimumab, and anti-PD-1 therapy “K drug” pembrolizumab.

Patients were randomly assigned to receive drug or placebo treatment at a ratio of 2:1. The primary endpoint was OS, and the key secondary endpoints were progression-free survival, objective remission rate, time to remission, and disease control rate.

The results of the interim analysis showed:

Compared with other therapies, the current one-year survival period of the tebentafusp treatment group is 73%, which is significantly better than the 58% of the other treatment groups. Reached its main clinical endpoint. However, the current data is not yet fully mature.

In addition, Tebentafusp also reduced the risk of death by 49%, compared to 6% for dacarbazine, 12% for ipilimumab, and 82% for pembrolizumab, reaching a statistically significant pre-defined cutoff. .

For metastatic uveal melanoma, a cancer with a very low survival rate, TCR therapy Tebentafusp significantly improves the survival of these patients. Good doctors learned that the therapy is expected to submit a marketing application in the third quarter of this year. It is hoped that the new treatment will be approved as soon as possible and benefit more patients.