Innovent explores cytokine space, linking fusion protein to tumor responses in study

Innovent Biologics has reported promising results for its bispecific immuno-oncology candidate, IBI363, in a small group of Chinese patients with lung cancer. This experimental drug has shown a 100% response rate among six patients with squamous non-small cell lung cancer (NSCLC).

IBI363 is a bispecific antibody fusion protein designed to merge the effects of an anti-PD-1 drug and an IL-2 cytokine into one molecule. This combination aims to block the PD-1 checkpoint and revitalize exhausted tumor-specific T cells, a strategy inspired by the failed collaboration between Bristol Myers Squibb (BMS) and Nektar Therapeutics. BMS and Nektar's attempt involved administering the two drugs separately, whereas Innovent’s approach unites them into a single therapeutic agent.

Two weeks ago, Innovent shared early data from a phase 1 trial of IBI363, conducted at a single hospital in China. The company recently presented more mature data at the 2024 ESMO Virtual Plenary, indicating the drug's potential in treating NSCLC.

The trial involved nine NSCLC patients who were administered 3 mg/kg of IBI363, a dosage that demonstrated rising efficacy. Among these patients, eight had previously been treated with checkpoint inhibitors like Keytruda, and one had received a T-cell engager.

Results showed that seven patients experienced partial responses to IBI363. Notably, all six patients with squamous NSCLC responded positively to the treatment. Additionally, one out of three patients with driver gene wild-type adeno NSCLC also showed a response. Overall, Innovent reported a nearly 50% response rate among the 15 patients who received 3 mg/kg of IBI363 and had undergone at least one post-baseline tumor assessment.

Dr. Hui Zhou, Senior Vice President at Innovent, expressed optimism about the drug's potential, highlighting its significant anti-tumor effects in NSCLC. He suggested that IBI363 could represent a breakthrough in the treatment of this type of lung cancer. Nevertheless, he acknowledged that the data sample is small and that early successes in immuno-oncology studies do not always translate into later-phase efficacy.

The history of IL-2 cytokine-based therapies serves as a cautionary tale. Nektar Therapeutics, for example, reported a 60% response rate in 37 subjects during a phase 1 trial and secured a $1.85 billion upfront payment from BMS. Despite this, their pivotal test failed, leading to a retreat from the IL-2 cytokine approach due to its toxicity and short half-life.

Innovent has endeavored to enhance the therapeutic window of IL-2 and combine it with a PD-1 checkpoint inhibitor to form a bispecific protein. The latest study data demonstrates signs of efficacy across various tumor types and so far, has not raised any significant safety concerns. Encouraged by these findings, Innovent plans to continue its efforts in treating NSCLC, melanoma, and other cancers.