ASCO24: Nimbus Charts Path for Next-Gen IO Therapies with Promising Early HPK1 Blocker Data

Nimbus Therapeutics has announced significant potential for its small molecule drug candidate, NDI-101150, in treating patients with advanced solid tumors. Detailed results from a Phase I/II clinical trial, which will be presented at the American Society of Clinical Oncology annual meeting, indicate that 16.7% of the evaluable patients experienced clinical benefits from the monotherapy. Out of 30 patients, five showed positive clinical outcomes.

One case highlighted a patient with renal cell carcinoma (RCC) achieving a complete response, meaning the tumor and other cancer signs had disappeared. Another RCC patient in the dose-expansion cohort exhibited a partial response. Both of these patients had previously undergone several treatment lines, including checkpoint inhibitors. Additionally, three patients maintained stable disease for over six months, including those with RCC, pancreatic cancer, and endometrial cancer.

Regarding safety, Nimbus reported that NDI-101150 was well-tolerated, with an acceptable safety profile. The most frequent side effects were nausea, vomiting, diarrhea, and fatigue. Approximately 12.8% of treated patients encountered grade 3 or higher treatment-related adverse events.

Despite the 16.7% clinical benefit rate, Nimbus' Chief Medical Officer Nathalie Franchimont expressed optimism about the results, highlighting HPK1 as a promising target for next-generation immunotherapies for solid tumors. Franchimont emphasized that NDI-101150 is a potent and selective HPK1 inhibitor with the potential for significant tumor growth inhibition and a meaningful impact on patients.

NDI-101150 is designed to be an orally available, reversible HPK1 inhibitor that enhances the activation of T cells, B cells, and dendritic cells. This mechanism allows the body to mount a robust anti-tumor response even under immunosuppressive conditions, as described on Nimbus’ website. The drug candidate is Nimbus' sole candidate currently in clinical trials, focusing on solid tumor treatment. The Phase I/II study not only demonstrated clinical benefits but also aimed to verify the drug’s mechanism of action. Biopsy samples from an RCC patient in the study revealed increased infiltration of activated CD8-positive T cells and dendritic cells compared to archival biopsies.

Another segment of the study explores the combination of NDI-101150 with Merck’s Keytruda (pembrolizumab). This announcement follows more than a year after Nimbus sold its oral TYK2 inhibitor zasocitinib and its subsidiary Nimbus Lakshmi to Takeda for an upfront payment of $4 billion, with up to $2 billion additional contingent on sales milestones.