Dr Taylor on Preliminary Efficacy and Safety Data for IO-108 in Advanced Solid Tumors

Matthew H. Taylor, MD, medical director, Providence Cancer Institute Thyroid Cancer Program, co-medical director, Providence Cancer Institute Melanoma Program, Earle A. Chiles Research Institute, Providence Cancer Institute, discusses the preliminary data on the use of IO-108 in advanced solid tumors in a phase 1 study (NCT05054348).

In the dose-escalation portion of this trial, the fully humanized IgG4 antibody IO-108 was evaluated as both a monotherapy and in combination with pembrolizumab (Keytruda), Taylor begins. The primary objective of the trial was safety and tolerability, which was measured by the incidence of treatment-emergent adverse effects (TEAEs) and TEAE-related discontinuation, he expands. Determination of the maximum-tolerated dose (MTD) was also a primary end point in this portion. Key secondary end points included antitumor activity, disease control rates, immunogenicity and both steady state and maximum plasma concentration for IO-108.

Safety data showed that IO-108 is well tolerated in this patient population, Taylor reports. No dose-limiting toxicities were observed. Moreover, the MTD was not reached, and dose-escalation reached up to 1800 mg intravenously every 3 weeks.

Regarding efficacy, IO-108 did elicit responses as both a monotherapy and in the combination regimen, Taylor states. Objective response rates (ORRs) were 9.1% (n = 11) and 23.1% (n = 13) in these cohorts, respectively. Partial responses were seen in 2 patients with microsatellite stable cholangiocarcinoma and 1 patient with microsatellite stable colorectal cancer. Moreover, 1 patient with advanced/metastatic Merkel cell carcinoma achieved a complete response as of the data cutoff date on March 13, 2023, Taylor adds. Notably, this patient had previously progressed on pembrolizumab in the metastatic setting. Subsequent treatment with ipilimumab (Yervoy) and nivolumab (Opdivo) again resulted in disease progression. This patient experienced a response with IO-108 monotherapy, indicating its activity, Taylor emphasizes.

Based on these data, 1200 mg has been chosen as the recommended phase 2 dose for this therapy, Taylor says. Going forward, this will be utilized in planned expansion cohorts for both IO monotherapy and IO plus other immune checkpoint inhibitors in solid tumors, he concludes.