First Patient Dosed With IO-108 in Phase 1b/2 HCC Trial

Human liver anatomy: © nerthuz - stock.adobe.com

The first patient with locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) has been dosed with IO-108 in phase 1b/2 trial.¹

The global, randomized study will evaluate IO-108, a first-in-class antibody that targets LILRB2, in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin) for the first-line treatment of patients with locally advanced or metastatic and/or unresectable HCC with no prior systemic treatment. The study plans to enroll 40 patients across 25 sites globally who will receive IO-108 with atezolizumab bevacizumab, while the other arm of the study will treat patients with just atezolizumab and bevacizumab.

The primary end point of the study is objective response rate, and key secondary end points include progression-free survival and overall survival.

“IO-108 has demonstrated promising clinical efficacy as a single agent and has a well-established safety profile to combine with different standard of care regimens. Dosing the first patient in this trial represents a significant advancement for Immune-Onc and, more importantly, for people battling advanced liver cancer,” said Charlene Liao, PhD, chief executive officer of Immune-Onc, in a press release. “We are excited to work with Roche to investigate how this combination therapy with IO-108 could enhance the current standard of care and offer improved outcomes for those who urgently need new therapeutic options.”

Atezolizumab plus bevacizumab is currently FDA-approved for the treatment of patients with HCC and is the standard of care recommended by the National Comprehensive Cancer Network. The approval was supported by findings from the phase 3 IMbrave150 clinical trial, where the combination reduced the risk of death by 42% (HR, 0.58; 95% CI, 0.42-0.79; P = .0006) compared with sorafenib (Nexavar) alone.² The combination also reduced the worsening of disease or death by 41% (HR, 0.59; 95% CI, 0.47-0.76; P <.0001) vs sorafenib.

About IO-108

According to the press release, IO-108 may reduce immune suppression and enhance the overall antitumor response in this patient population, potentially improving patient outcomes.¹ In a phase 1 dose-escalation study of IO-108 (NCT05054348), which was published in the Journal for ImmunoTherapy of Cancer, the agent demonstrated encouraging clinical benefit when used as a monotherapy and in combination with anti–PD-1 across multiple tumor types.³

Among the 25 patients enrolled in the study, 12 were given IO-108 alone and 13 received combination therapy. Up to the maximally administered dose of 1800 mg every 3 weeks, IO-108 as monotherapy and in combination with pembrolizumab (Keytruda) was shown to be well tolerated with no dose-limiting toxicities observed. A maximum tolerated dose of the agent was not reached.

The overall response rate was 9% in the monotherapy and 23% in the combination therapy. Additionally, a patient with treatment-refractory Merkel cell carcinoma who was given IO-108 as a monotherapy achieved a durable complete response (CR) for more than 2 years.

A favorable safety profile was also observed with treatment-related adverse events (TRAEs) occurring in 6 (50.0%) patients in the IO-108 monotherapy arm and 6 (46.2%) patients in the IO-108 plus pembrolizumab arm. All TRAEs were mild or moderate, and none led to treatment discontinuation or death.

REFERENCES:

1. Immune-Onc Therapeutics announces first patient dosed with IO-108 in a randomized global phase 1b/2 study of first-line treatment of advanced liver cancer in clinical collaboration with Roche. News release. February 27, 2025. Accessed February 27, 2025. https://tinyurl.com/3rj825my

2. FDA approves Genentech’s Tecentriq in combination with Avastin for people with the most common form of liver cancer. Published May 29, 2020. Accessed February 27, 2025. https://bit.ly/2Aneztc

3. Taylor MH, Naing A, Powderly J, et al. Phase I dose escalation study of IO-108, an anti-LILRB2 antibody, in patients with advanced solid tumors. J Immunother Cancer. 2024;12(11):e010006. Published 2024 Nov 20. doi:10.1136/jitc-2024-010006