Phase 3 Trial of First-Line IO102-IO103/Pembrolizumab to Continue in Advanced Melanoma

Mai-Britt Zocca, PhD

The phase 3 IOB-013/KN-D18 trial (NCT05155254) evaluating IO102-IO103 in combination with pembrolizumab (Keytruda) for the first-line treatment of patients with advanced melanoma will continue without modifications following a recommendation from an independent data monitoring committee (IDMC).¹

In a review of safety and efficacy data at a per-protocol interim analysis conducted 1 year after 225 patients were randomly assigned, the IDMC reported no new safety signals. Overall response rate (ORR) data did not meet the criteria to declare superiority for IO102-IO103 plus pembrolizumab vs pembrolizumab alone; however, the study sponsor, IO BioTech, noted in a news release that the interim efficacy analysis for ORR included a high statistical bar (P ≤ .005).

An analysis of progression-free survival (PFS)—the study’s primary end point—will be conducted when 226 disease progression events or deaths are reported, which is projected to occur in the first half of 2025.

“To date, none of the approved immunotherapeutic combinations for the treatment of advanced melanoma demonstrated statistical significance in ORR in large phase 3 trials; nevertheless, these trials achieved statistical significance on PFS,” Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech, stated in a news release. “Based on the 25.5-month median PFS we observed in the phase 1/2 trial [NCT03047928] of IO102-IO103 in combination with a PD-1 inhibitor in advanced melanoma, with no added significant systemic toxicity than that typically seen with anti–PD-1 monotherapy, we remain optimistic about meeting the primary end point of PFS [in the phase 3 trial].”

IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine intended to kill tumor cells and immune-suppressive cells in the tumor microenvironment through the activation and expansion of T cells targeted against IDO-positive and/or PD-L1–positive cells.

IOB-013/KN-D18 enrolled patients at least 18 years of age with histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma who were naive to systemic therapy in the unresectable or metastatic setting.² Patients harboring BRAF V600 mutations were allowed to enroll if they did not have rapidly progressive disease. Those who received neoadjuvant and/or adjuvant therapy with targeted therapy or immune therapy were allowed to enroll if the last dose of treatment was given at least 6 months prior to enrollment on the phase 3 study and if relapse did not occur during treatment or within 6 months of discontinuation. All patients were required to have at least 1 measurable lesion per RECIST 1.1 criteria.

Key exclusion criteria consisted of known or suspected central nervous system metastases, unless patients had stable brain metastases; radiotherapy within 2 weeks of enrollment; and BRAF V600–mutated disease that was rapidly progressing or was treated in the first-line unresectable or metastatic setting with a BRAF inhibitor and/or a MEK inhibitor.

Patients were randomly assigned to receive 200 mg of pembrolizumab once every 3 weeks for up to 35 cycles with or without IO102-IO103. In the experimental arm, the vaccine was given at 85 µg once every 3 weeks for up to 35 cycles, and an additional dose was given on day 8 of cycles 1 and 2, translating to a maximum of 37 doses over 2 years.

The primary end point was PFS per RECIST 1.1 criteria, and secondary end points included ORR, overall survival, durable ORR, complete response (CR) rate, duration of response, time to response, time to CR, disease control rate, and safety.

Along with the phase 3 trial in advanced melanoma, the combination of IO102-IO103 and pembrolizumab is being evaluated in the phase 2 IOB-022/KN-D38 basket trial (NCT05077709) for the first-line treatment of patients with solid tumors, as well as in the phase 2 IOB-032/PN-E40 basket trial (NCT05280314) as neoadjuvant and adjuvant treatment for patients with solid tumors.¹

References

1. IO Biotech updates on pivotal phase 3 trial of IO102-IO103 in combination with Keytruda (pembrolizumab) as a first-line treatment for patients with advanced melanoma. News release. IO Biotech. August 30, 2024. Accessed September 4, 2024. https://iobiotech.com/press-releases/?workflow=89099b13-d881-4ba9-bbe0-25608d3a5edb
2. IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in advanced melanoma (IOB-013 /​ KN-D18). ClinicalTrials.gov. Updated January 9, 2024. Accessed September 4, 2024. https://clinicaltrials.gov/study/NCT05155254