Inhibrx has announced results from Part 1 of the Phase 1 dose escalation trial of INBRX-106, a novel hexavalent OX40 agonist, in development for the treatment of solid tumors.

The trial is a first-in-human, multicenter, open-label, non-randomized, 4-part Phase 1 trial in patients with locally advanced or metastatic solid tumors designed to determine the safety profile and identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose of INBRX-106 administered as a single agent or in combination with Keytruda? (pembrolizumab), a programmed death receptor-1 (PD-1) checkpoint inhibitor.

The single-agent dose escalation part of this Phase 1 trial enrolled 20 patients. In this Phase 1 trial, INBRX-106 was observed to be well tolerated, with mostly mild or moderate immune-related toxicities noted, in line with the mechanism of action of this candidate therapeutic. The maximum administered dose was 3 mg/kg and the MTD level was not reached. Signs of clinical benefit to date were observed in patients with a range of tumor types, including those generally considered to be hot and cold, as well as in individuals that were relapsed or refractory to checkpoint inhibitors. Activity was observed at dose levels in a range from 0.0003 to 0.3 mg/kg and peripheral biomarker sampling confirmed agonist activity across these low doses. With the conclusion of Part 1 (the single agent dose escalation), Part 2 (single-agent expansion) and Part 3 (combination dose escalation) of the trial will both be initiated this month.

In the Part 2 expansion cohort, the 0.03 mg/kg dose level administered in various dosing schedules will be investigated in patients with tumor types generally responsive to checkpoint inhibitors. Key attributes leading to the choice of this dose level include rapid loss of OX40 after dosing, evidence of peripheral memory T cell activation and proliferation, and sufficient drug clearance to allow target recovery prior to the next dose administration.

In the Part 3 combination dose escalation cohort, INBRX-106 will be evaluated in combination with Keytruda . Preclinical data suggests INBRX-106 may have improved anti-tumor activity with concurrent blockade of the PD-1 checkpoint. Efficacy and safety data from the combination escalation cohort are expected to be reported in the second half of 2021, at which time and assuming positive results, Part 4, the combination expansion cohort, will begin in NSCLC and other tumor types generally responsive to checkpoint inhibitors.

"We believe the early activity of single agent INBRX-106 that we observed at low doses is encouraging and aligns with our preclinical data, which described a bell-shaped dose response curve and potent OX40 agonist activity," said Mark Lappe, CEO of Inhibrx. "We are excited to move into the combination phase of the trial to evaluate if the addition of Keytruda will accentuate the anti-tumor activity of INBRX-106 and potentially expand the patient population responsive to checkpoint inhibition."

INBRX-106 is a hexavalent product candidate agonist of OX40. OX40 is a co-stimulatory receptor expressed on immune cells that is enriched in the tumor microenvironment. OX40 ligand is a trimeric protein that activates OX40 signaling through clustering. INBRX-106 was engineered to bind and cluster six OX40 receptors and has been shown preclinically to significantly outperform bivalent antibodies in co-stimulatory capacity and anti-tumor activity.