How effective is an immunomodulatory vaccine against PD-L1 /IDO in combination with nivolumab for the treatment of metastatic melanoma?

The study aimed to evaluate the safety and effectiveness of an immunomodulatory IDO/PD-L1 targeting peptide vaccine (IO102/IO103) combined with nivolumab (Opdivo) in patients with metastatic melanoma (MM). The study concluded that the IO102/IO103 vaccine combined with nivolumab is safe and effective in these patients.

Immunotherapy is a type of cancer treatment that makes use of the immune system to fight cancer. The cancer cell has some proteins present on the surface that help to turn off the immune system by binding proteins on the surface of the immune cells such as PD-1/PD-L1 or CTLA4. Immune checkpoint inhibitors (ICI) such as nivolumab block these interactions and turns on the immune system to attack and kill the cancer cells.

Melanoma is one of the most aggressive forms of skin cancer. Recent use of anti-PD-1/L1 plus anti-CTLA-4 treatment showed effective results in MM. However, half of the patients are resistant to ICI therapy alone and develop serious side effects. Cancer vaccines are currently being developed. The Immunomodulatory IO102/IO103 vaccine finds specific immune cells in the blood of patients with cancer and directly targets and kills cancer cells that express (have on their surface) certain cancer proteins. 

The safety and effectiveness of the IDO/PDL-1 peptide vaccine combined with nivolumab in patients with MM are still unknown. 

The study involved 30 patients with MM melanoma who have not undergone prior treatment with ICIs. Patients received six doses of the IO102/IO103 vaccine every 2 weeks and up to 15 doses every 4 weeks thereafter. Nivolumab was also given every 2 to 4 weeks to patients at the same time as the vaccine for up to 2 years. The average follow-up was 22.9 months.

Overall, 80% of patients showed treatment response. A complete response (complete disappearance of cancer signs) was observed in 43% of patients and 37% of patients showed partial responses. The response rate was higher in patients with PD-L1 positive tumors (94%) compared to patients with tumors not expressing PD-L1 protein (PD-L1 negative; 61.5%). More than 93% of patients showed increased response after vaccination by activating the specific immune cell that targets cells related to tumor and immunosuppression.

At 12 months 87% of patients responding to treatment were free from cancer progression. The average survival without cancer progression was 26 months for all patients and was not reached for those who responded to treatment (extended the follow-up period). After 12 months, 81.6% of patients were alive.

The most common side effects were tiredness, diarrhea, dry skin, nausea, joint stiffness, and itchiness. 13% of patients experienced serious side events such as rash, adrenal insufficiency, and joint pain. 

This study showed that IDO/PD-L1 vaccination combined with nivolumab immunotherapy is effective and well-tolerated in patients with MM.

This study had a small number of participants and did not have a comparison group. The study was supported by IO Biotech, USA, the manufacturer of the IO102/IO103 vaccine.