Nimbus Therapeutics Shares Positive Phase 1/2 Data on HPK1 Inhibitor for Advanced Tumors at 2024 ASCO Meeting

Nimbus Therapeutics, a biotech firm known for its innovative approach to drug discovery, has announced promising data from its ongoing Phase 1/2 clinical trial of NDI-101150. This new oral medication, a potent small-molecule inhibitor targeting hematopoietic progenitor kinase 1 (HPK1), is being developed for the treatment of advanced solid tumors. The findings were showcased at the American Society of Clinical Oncology (ASCO) Annual Meeting, which took place from May 31 to June 4, 2024, in Chicago, Illinois.

The multicenter, open-label trial is assessing NDI-101150 both as a standalone treatment and in combination with pembrolizumab, an established immunotherapy, across a range of dosing regimens. Specifically, the trial includes monotherapy doses ranging from 50 to 200 mg, and a fixed 200 mg dose in combination with pembrolizumab. The updated data presented at the meeting covered 44 patients, including 38 receiving monotherapy and six receiving combination therapy, with an additional 15 patients from the dose expansion cohorts.

As of mid-March 2024, the study revealed several key outcomes:
- Monotherapy with NDI-101150 demonstrated clinical benefits in five of 30 patients (16.7%) who were evaluable for response.
- One patient with renal cell carcinoma (RCC) in the dose escalation group achieved a complete response, while another RCC patient in the dose expansion group showed a partial response. Both patients had previously undergone multiple lines of treatment, including checkpoint inhibitors.
- Three patients with RCC, pancreatic cancer, and endometrial cancer experienced durable stable disease for over six months, with the RCC patient maintaining this status for 21 months.
- Among RCC patients, six out of eight evaluable patients experienced stable disease or better as their best overall response.
- NDI-101150 treatment was linked to an increase in activated CD8+ T cells and dendritic cell infiltration in tumor biopsies, corroborating preclinical studies that indicated significant immune cell infiltration and anti-tumor activity in murine models.
- The safety profile of NDI-101150 was deemed acceptable, with the drug being well-tolerated by patients.

Dr. Nathalie Franchimont, Chief Medical Officer at Nimbus, expressed optimism about these findings. She emphasized that the positive data supports HPK1 inhibition as a viable next-generation immunotherapy target, particularly for individuals with advanced solid tumors requiring new treatment options. HPK1 inhibition, she explained, uniquely activates T cells, B cells, and dendritic cells to mount a robust anti-tumor response, unlike currently approved checkpoint inhibitors that primarily activate T cells. NDI-101150’s potential to significantly inhibit tumor growth could offer meaningful benefits to patients.

Nimbus Therapeutics operates at the forefront of structure-based drug discovery, leveraging state-of-the-art computational technologies and machine learning-based predictive modeling. The company's pipeline includes various promising candidates, notably the clinical-stage HPK1 inhibitor NDI-101150, aimed at treating cancer, autoimmune conditions, and metabolic diseases.

The detailed findings from the trial were made available in a poster presentation by lead author Dr. Marcus Noel during the ASCO meeting. These results underscore the potential of NDI-101150 to become a crucial advancement in cancer treatment, offering hope to patients with few effective options.