Innovent braves bruising cytokine space, linking fusion protein to tumor responses in small study

Innovent Biologics' bispecific immuno-oncology candidate IBI363 has been linked to a 100% response rate in a small cohort of Chinese lung cancer patients.

IBI363 is a bispecific antibody fusion protein built on similar thinking to Bristol Myers Squibb’s doomed alliance with Nektar Therapeutics. While BMS and Nektar studied the effects of giving an anti-PD-1 drug and IL-2 cytokine in combination, Innovent has brought the two parts together into a single molecule. The idea is to block the PD-1 checkpoint and rejuvenate exhausted tumor-specific T cells.

Innovent shared an early look at data from a phase 1 trial of wholly owned IBI363, which is taking place at a single Chinese hospital, two weeks ago. The biotech arrived at the 2024 ESMO Virtual Plenary with a later cut of the data that points to the promise of the drug in non-small cell lung cancer (NSCLC).

The data includes nine NSCLC patients who received 3 mg/kg of IBI363, the dose above which Innovent has seen efficacy rise. Eight of the patients had previously received a checkpoint inhibitor such as Keytruda. One patient had received a T-cell engager.

Seven patients had partial responses to IBI363. All six patients with squamous NSCLC responded to the drug candidate. Innovent saw the other response in one of the three patients with driver gene wild-type adeno NSCLC. Across all tumor types, Innovent reported a response rate of almost 50% in the 15 patients who received 3 mg/kg of IBI363 and had at least one post-baseline tumor assessment.

Hui Zhou, Ph.D., senior vice president at Innovent, said in a statement that anti-tumor effects in NSCLC suggest IBI363 could “potentially be the next breakthrough in this area.” However, the 3 mg/kg data set is small, and history shows promising data in early immuno-oncology studies can fail to translate into late-phase efficacy. 

Nektar reported a 60% response rate in 37 subjects in phase 1, landed a $1.85 billion upfront payment from BMS and still failed spectacularly in its pivotal test. The failure precipitated a broader retreat from IL-2, a cytokine that became the first approved immuno-oncology drug decades ago but has had limited impact because of its toxicity and short half-life. 

Innovent has worked to improve the therapeutic window of IL-2 and package it with a PD-1 checkpoint inhibitor to create a bispecific protein. With the study revealing signs of efficacy in multiple tumor types, and being free from safety red flags so far, the Chinese drugmaker is forging ahead in NSCLC, melanoma and other indications.