Nurix Therapeutics' NX-1607 Shows 49.3% Disease Control Rate in First-in-Class CBL-B Inhibitor Trial
核心洞察
Nurix Therapeutics reported Phase 1a data for NX-1607, a first-in-class oral CBL-B (搜索) inhibitor, demonstrating a 49.3% disease control rate across 82 heavily pretreated patients with advanced solid tumors (搜索).
The drug showed notable activity in microsatellite stable colorectal cancer (搜索) and prostate cancer (搜索), tumor types typically unresponsive to current immunotherapies, with one patient achieving a partial response lasting 27 months.
NX-1607 demonstrated dose-dependent immune activation and anti-tumor activity with a tolerable safety profile comparable to approved immuno-oncology agents, supporting expansion cohorts at higher doses.
Nurix Therapeutics presented encouraging Phase 1a clinical data for NX-1607, a first-in-class oral inhibitor of the E3 ligase CBL-B (搜索), at the European Society for Medical Oncology Congress (ESMO 2025) in Berlin. The trial enrolled 82 patients with eleven different tumor types across dosing regimens ranging from 5 mg to 80 mg total daily dose, achieving a disease control rate of 49.3% in heavily pretreated patients with advanced solid tumors (搜索).
Novel Mechanism Targets Multiple Immune Cell Types
NX-1607 represents a new approach to immuno-oncology by inhibiting CBL-B (搜索), a cytoplasmic E3 ubiquitin ligase that negatively regulates T cell activation. Unlike conventional PD-1/PD-L1 therapies, this mechanism affects multiple immune cell types including dendritic cells and natural killer cells, which play critical roles in the tumor microenvironment.
"As a first-in-class oral inhibitor of CBL-B (搜索), NX-1607 may offer a novel therapeutic approach to treat solid tumors (搜索) by targeting a previously unaddressed pathway in immune regulation," said Paula O'Connor, M.D., chief medical officer of Nurix.
Clinical Activity in Treatment-Resistant Tumor Types
The study population consisted of heavily pretreated patients with a median of 3 prior regimens, including a median of 1 prior chemo/immunotherapy regimen. Despite the advanced disease stages and broad range of tumor types, NX-1607 demonstrated evidence of clinical activity including reductions in tumor-specific biomarkers such as prostate-specific antigen (PSA) in prostate cancer (搜索) and carcinoembryonic antigen (CEA) in colorectal cancer (搜索).
Particularly notable was a confirmed partial response in a patient with microsatellite stable colorectal cancer (搜索) (MSS CRC), a tumor type typically unresponsive to immune checkpoint therapy. This patient achieved a partial response and was treated for 27 months. Additionally, 7 patients achieved either stable disease or partial response for ≥5 months on treatment.
In prostate cancer (搜索) patients, the greatest PSA reductions were achieved in the twice-daily dosing groups, with 6 of 13 patients experiencing PSA reductions of ≥50%, supporting the dose-dependent activity of NX-1607.
Safety Profile and Immune Activation
NX-1607 demonstrated a safety profile comparable to approved immuno-oncology agents, with most adverse events Grade 2 or less in severity. The most common treatment-emergent adverse events included nausea and vomiting, which were mitigated by twice-daily dosing and a step-up dosing regimen where patients initially received lower doses before escalating to target doses.
Immune-related adverse events were observed in 6 patients, indicating on-target immune activation similar to what is observed with PD-1/PD-L1 therapies. The drug demonstrated dose-dependent exposure, increases in proximal and distal biomarkers, and evidence of peripheral immune activation.
Development Strategy and Future Plans
The data support initiation of expansion cohorts at the two highest doses tested as monotherapy or combination therapy for advanced solid tumors (搜索). Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, emphasized the significance of the results in MSS colorectal cancer (搜索) and metastatic prostate cancer (搜索), "two important indications where current immunotherapies have failed to demonstrate efficacy."
The company plans to continue exploring NX-1607's therapeutic potential while advancing its lead asset bexobrutideg (搜索), an oral BTK (搜索) degrader, into pivotal trials for patients with relapsed or refractory chronic lymphocytic leukemia (搜索). The ongoing Phase 1 trial includes a thorough investigation of both dose and schedule optimization in the Phase 1a portion.