Tebentafusp is an immunotherapy drug, representing a new class of treatments for certain cancers. It is classified as a bispecific fusion protein, meaning it has two distinct parts designed for specific functions. This innovative medicine works by harnessing the body’s own immune system to target and combat cancer cells, offering a unique approach by redirecting immune cells to tumor sites.
How Tebentafusp Works
Tebentafusp functions as a molecular matchmaker, bridging the body’s immune cells and cancer cells. One part of this fusion protein binds to gp100, a protein found on melanoma cells, but only when gp100 is presented with HLA-A\02:01. The other part binds to the CD3 receptor on T-cells. By connecting the melanoma cell to a T-cell, tebentafusp brings the immune cell into direct contact with the cancer cell. This activates the T-cell, prompting it to release inflammatory cytokines and other proteins that directly attack and destroy the targeted cancer cell.
Approved Use for Tebentafusp
Tebentafusp is approved for treating adults with unresectable or metastatic uveal melanoma, a rare and aggressive eye cancer that has spread or cannot be surgically removed. A defining characteristic for its use is a genetic requirement: patients must be HLA-A\02:01-positive. Human leukocyte antigens (HLAs) are proteins on cell surfaces that help the immune system recognize foreign substances. The drug’s design relies on this specific HLA-A\02:01 variant to properly present the gp100 protein on the cancer cell surface, allowing the drug to bind and initiate an immune response.
Administration and Patient Monitoring
Tebentafusp is administered as a weekly intravenous (IV) infusion, typically taking 15 to 20 minutes. Dosing begins with escalating amounts: 20 micrograms on Day 1, 30 micrograms on Day 8, and 68 micrograms on Day 15 and weekly thereafter. Close patient monitoring is required during initial treatment due to potential immediate side effects. The first three infusions are given in a healthcare setting, with patients observed for at least 16 hours after each dose to allow providers to promptly manage any reactions. If no significant issues arise after the third infusion, subsequent doses may be given outpatient with a shorter monitoring period of at least 30 minutes.
Potential Side Effects
Patients receiving tebentafusp may experience side effects, with Cytokine Release Syndrome (CRS) being a primary concern. CRS is an inflammatory response from activated immune cells releasing cytokines, and symptoms include fever, chills, low blood pressure, difficulty breathing, fatigue, headache, and nausea. This reaction typically occurs within the first few infusions and is closely monitored. Other common adverse reactions include skin issues like rash, itching, and swelling, linked to gp100 expression in normal skin cells, along with fatigue, nausea, vomiting, abdominal pain, and edema. Elevations in liver enzymes have also been observed, especially within the first three infusions, requiring regular blood tests to monitor liver function.
Clinical Trial Outcomes
The efficacy of tebentafusp was demonstrated in a Phase 3 clinical trial (IMCgp100-202) involving HLA-A\02:01-positive patients with previously untreated metastatic uveal melanoma, which assessed overall survival. Patients receiving tebentafusp showed a statistically significant improvement in overall survival compared to those who received standard therapies like pembrolizumab, ipilimumab, or dacarbazine. The one-year overall survival rate in the tebentafusp group was approximately 73%, compared to 59% in the control group. Longer-term data, with a minimum follow-up of 36 months, showed a median overall survival of 21.6 months for the tebentafusp group versus 16.9 months for the control group. This sustained improvement in survival highlights the benefit of tebentafusp for patients with this challenging cancer.