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

Nimbus Therapeutics’ small molecule drug candidate, NDI-101150, has shown promising potential for clinical benefit in patients with advanced solid tumors, the Boston-based biotech announced on Thursday.

Results from a Phase I/II study, to be presented at the American Society of Clinical Oncology annual meeting next week, revealed that five out of 30 evaluable patients (16.7%) experienced clinical benefit from NDI-101150 monotherapy. Notably, one patient with renal cell carcinoma (RCC) achieved a complete response, characterized by the disappearance of a tumor and other signs of cancer.

Additionally, another RCC patient in the dose-expansion cohort showed a partial response. Both of these patients had undergone several prior treatments, including checkpoint inhibitors.

Three other patients achieved and maintained stable disease for more than six months while on treatment with Nimbus’ drug candidate. These patients had RCC, pancreatic cancer, and endometrial cancer, respectively.

Regarding safety, Nimbus reported that NDI-101150 was “well-tolerated” with an overall safety profile that “remains acceptable.” According to the study’s abstract, 12.8% of treated patients experienced grade ≥3 treatment-related adverse events, with the most common side effects being nausea, vomiting, diarrhea, and fatigue.

While a 16.7% clinical benefit rate might seem modest, Nimbus CMO Nathalie Franchimont stated that the biotech is “encouraged” by these early data, which highlight HPK1 as a promising next-generation immunotherapy target for solid tumors.

“NDI-101150 is a potent and highly selective HPK1 inhibitor that has the potential to achieve significant tumor growth inhibition and make a meaningful difference for patients,” Franchimont added.

Designed to be orally available, NDI-101150 is a reversible HPK1 inhibitor that enhances the activation of T cells, B cells, and dendritic cells, enabling the body to “mount a robust anti-tumor response, even under immunosuppressive conditions,” according to Nimbus’ website.

NDI-101150 is Nimbus’ only candidate in clinical trials and is being developed as a treatment for solid tumors. Besides its clinical benefit, the Phase I/II study also aimed to verify its mechanism of action. Using biopsy samples from an RCC patient, Nimbus observed “increased infiltration” of activated CD8-positive T cells and dendritic cells compared to archival biopsies, according to the abstract.

Another part of the study is testing the combination of NDI-101150 with Merck’s Keytruda (pembrolizumab).

Thursday’s update comes over a year after Nimbus sold its oral TYK2 inhibitor zasocitinib—along with its wholly owned subsidiary Nimbus Lakshmi—to Takeda for $4 billion upfront, plus potentially $2 billion more contingent on annual sales milestones.