Data from a phase 1 trial found that the maximum-tolerated dose of INBRX-106 for metastatic solid tumors is 0.1 mg/kg once every 3 weeks.
INBRX-106 in combination with pembrolizumab (Keytruda) showed clinical activity for the treatment of patients with solid tumors, according to results of a phase 1 trial reported by Inhibrx, Inc.
INBRX-106 is a hexavalent product candidate agonist of OX40, which is a costimulatory receptor expressed on immune cells and enriched in the tumor microenvironment. INBRX-106 is meant to bind and cluster 6 OX40 receptors. Preclinical studies have found that the agent significantly outperforms bivalent antibodies in both co-stimulatory capacity and anti-tumor activity.
The trial (NCT04198766) has an estimated enrollment of 150 participants and an estimated study completion date of March 2023. Primary end points of the study include the frequency of adverse events associated with INBRX-106 as both a monotherapy and in combination with pembrolizumab, severity of adverse events, and maximum tolerated dose. Secondary end points include area under the serum concertation time curve, maximum observed serum concentration, and immunogenicity. Other end points explored include anti-tumor activity.
The phase 1 study is made up of 4 parts. During part 1, patients with locally advanced or metastatic solid tumors received escalating doses of INBRX-106 monotherapy. In part 2, patients received INBRX-106 monotherapy and were stratified by tumor type. In part 3, patients with metastatic solid tumors received escalating doses of INBRX-106 in combination with pembrolizumab. In part 4, patients received the combination and were stratified by tumor type.
An analysis of part 3 found that the combination was found to be well tolerated, with mostly mild or moderate immune-related toxicities. The maximum administered dose of INBRX-106 was found to be 0.3 mg/kg. At this level, dose-limiting toxicities such as dermatitis was observed. The maximum tolerated dose was found to be 0.1 mg/kg dosed every 3 weeks in combination with pembrolizumab.
Of the 5 evaluable patients, 2 durable partial responses were observed in checkpoint inhibitor naïve nasopharyngeal carcinoma and uveal melanoma patients. Duration of response was found to be greater than 6 months with treatment ongoing. A third patient with checkpoint inhibitor exposed cutaneous melanoma had a double-digit reduction in tumor volume, with duration greater than 4 months with treatment ongoing.
"We believe the early activity of single agent INBRX-106 and INBRX-106 in combination with Keytruda observed in patients who relapsed or are refractory to checkpoint inhibitors as well as in patients with tumor types responsive to immunotherapy that respond poorly to checkpoint inhibitors is very encouraging" said Mark Lappe, chief executive officer of Inhibrx, in a press release. "We are pleased to see that our preclinical data, which demonstrated that hexavalent valency is required to properly agonize OX40, appear to be translating clinically."
In order to participate in the study, patients must be 18 years of age or older, and have a diagnosis of a solid tumor. Patients with prior exposure to OX40 agonists, a hematologic malignancy, active central nervous system tumors, active autoimmune disease, active interstitial lung disease, or a clinically significant cardiac condition are not eligible to participate.