Cancer Vaccines Get FDA Breakthrough Status in Advanced Melanoma Combo Therapy

Cancer Vaccines Get FDA Breakthrough Status in Advanced Melanoma Combo Therapy

The U.S. Food and Drug Administration (FDA) has granted the designation of breakthrough therapy to a combination treatment of IO Biotech’s lead anti-cancer vaccine candidates IO102 and IO103, plus an anti-PD-1 antibody-based immunotherapy, to treat patients with inoperable or metastatic melanoma.

This designation is given to accelerate the development, review, and possible approval of medications that aim to treat serious or life-threatening conditions and have the potential to provide significant advantages over current options.

“This is an important achievement for IO Biotech’s clinical program and we are committed to bring this forward to patients as soon as possible,” Mai-Britt Zocca, PhD, CEO and founder of IO Biotech, said in a press release.

IO102 and IO103 are based on the company’s proprietary T-win technology, a platform that helps identify compounds able to stop mechanisms used by cancer cells to evade immune attacks.

Both are immune modulatory vaccine candidates that activate and direct T-cells, which are immune cells able to fight cancer, against specific immunomodulatory proteins: indolamine 2,3 dioxygenase (IDO) in the case of IO102, or PD-L1 in the case of IO103.

IDO is an enzyme highly produced by immunosuppressive cells and cancer cells. It is exploited by the cancer cells as a mechanism to evade the body’s immune system. Similarly, PD-L1 is a signaling molecule cancer cells produce to avoid being targeted and eliminated by immune cells.

The effectiveness of these vaccine candidates is expected to be higher when combined with other immunotherapies designed to block the activity of PD-1, such as Opdivo (nivolumab). PD-1 is a protein receptor found on the surface of T-cells that interacts with PD-L1 and triggers a signaling cascade that makes it harder for T-cells to recognize and eliminate tumor cells.

The FDA’s decision to grant its breakthrough designation to the combination therapy was based on data from an ongoing Phase 1/2 trial, called MM1636 (NCT03047928). The study is investigating the safety and efficacy of a peptide vaccine containing both IO102 and IO103 in combination with Opdivo in patients with advanced melanoma.

Study participants will receive a total of 15 vaccinations. The first six administrations will be given in two-week intervals during the first three months of the study, and the remaining nine in four-week intervals for up to one year. At the same time, patients will receive Opdivo at a dose of 3 mg/kg every two weeks, until disease progression or unacceptable toxicity.

Data from MM1636, presented in a late-breaking abstract at the European Society for Medical Oncology Virtual Congress 2020, showed that the combination therapy was safe and led to promising treatment responses. Study findings included data from 30 patients followed for a median period of 15 months.

As of August, 29 participants were eligible for treatment response assessments, and 79% of them responded to treatment. The percentage of treatment responders was even higher (94%) in the subset of patients whose tumors contained PD-L1.

Nearly half (45%) of the patients achieved a complete response (complete cancer eradication), and around a third (34%) experienced a partial response (partial cancer elimination). Importantly, these values were much higher compared with those seen in a matched group of patients who were only treated with an anti-PD-1 immunotherapy as a standard of care.

Notably, patients remained alive and with no signs of disease worsening for a median of 25.6 months. Apart from local reactions, the toxicity profile of the combination therapy was identical to that of Opdivo as a stand-alone therapy.

Additional analyses also revealed the presence of T-cells primed against IDO and/or PD-L1 in the bloodstream of all treated patients. In some participants where tissue biopsies had been performed, these cells were also identified at the tumor site.

Top-line data from MM1636 is expected next year, and the study is scheduled to conclude by 2023.