ESMO: IO Biotech's vaccine-Keytruda combo meets primary endpoint in phase 2 SCC trial

In cancer therapy, immune checkpoint inhibitors like Bristol Myers Squibb’s Opdivo and Merck’s Keytruda have emerged as powerful treatments. Keytruda alone generated $25 billion last year, solidifying its status as the top-selling drug of 2023. However, even the most potent treatments can benefit from complementary therapies. At the 2024 European Society for Medical Oncology congress, Copenhagen-based IO Biotech showcased promising results for their IO102-IO103 cancer vaccine when combined with Keytruda (pembrolizumab). This combination treatment yielded an objective response rate of 44.4%, achieving the primary endpoint in a phase 2 trial involving patients with advanced squamous cell carcinoma of the head and neck (SCCHN).

Dr. Qasim Ahmad, Chief Medical Officer of IO Biotech, emphasized the potential of the IO102-IO103 and Keytruda combination as a first-line treatment for various cancers, including those that are metastatic and challenging to treat. The IO102-IO103 vaccine is a fusion of two vaccines designed to prime patients’ T cells to attack tumors. IO102 targets indoleamine-2,3-dioxygenase (IDO), an enzyme within cells, while IO103 aims at programmed death-ligand 1 (PD-L1), a membrane protein. Both IDO and PD-L1 assist cancer cells in evading the immune system, and by activating T cells against these targets, the aim is to enhance the body's natural defense mechanisms to combat cancer.

The IOB-022/KN-D38 phase 2 trial included 63 patients across different cancer types as of August 2, with 21 SCCHN patients. Patients with SCCHN treated with the vaccine and Keytruda saw a median progression-free survival of 6.6 months and a disease control rate of 66.7%. Adverse events were common, with 20 out of 21 patients experiencing side effects, mostly mild, such as rash, fatigue, and injection site reactions. One patient experienced a severe adverse event, immune thrombocytopenia, which was managed with corticosteroids. Notably, two patients discontinued treatment due to side effects like conjunctivitis and colitis, while another patient passed away from an unrelated illness during the trial, leaving 18 patients for data analysis.

Further data from patients with non-small cell lung cancer will be presented later this fall. IO Biotech retains global commercial rights to the IO102-IO103 vaccines, despite Merck's collaboration on the trials.

Alongside IO Biotech's vaccines, Merck is also testing other cancer vaccines to complement Keytruda. At the American Society of Clinical Oncology meeting in June, data was shared from a phase 2 trial of an mRNA vaccine developed with Moderna. In this study, the combination of the mRNA vaccine and Keytruda reduced the risk of recurrence or death by 49% in patients with resected melanoma when compared to Keytruda alone.

In 2021, IO Biotech secured $155 million in a series B funding round to advance its cancer vaccines. The company is also testing the IO102-IO103 vaccine in combination with Opdivo (nivolumab) and BMS' relatlimab in a phase 2 trial for untreated, unresectable melanoma. The vaccine-Opdivo combination received a breakthrough-therapy designation from the FDA in 2020.

Earlier this year at the World Vaccine Congress, Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research, highlighted the agency’s openness to reviewing new cancer vaccines, indicating a promising future for innovative cancer treatments.