On January 4, 2022 Inhibrx, Inc. (Nasdaq: INBX), a biotechnology company with four clinical programs in development and a strong emerging pipeline, reported initial results from Part 3 (combination dose escalation) of the 4-part Phase 1 trial of INBRX-106, a novel hexavalent OX40 agonist, in combination with Keytruda, in development for the treatment of patients with solid tumors (Press release, Inhibrx, JAN 4, 2022, View Source [SID1234598078]). Additionally, an update on single agent data from Part 1 (single agent dose escalation) and Part 2 (single agent dose expansion) of the trial was provided.
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In the all-comer Part 3 of this Phase 1 trial, the dose of INBRX-106 was escalated in combination with Keytruda in 21 patients with locally advanced or metastatic solid tumors. INBRX-106 in combination with Keytruda was observed to be well tolerated, with predominantly mild or moderate immune-related toxicities noted. The maximum administered dose of INBRX-106 was 0.3 mg/kg, at which dose-limiting, immune-related toxicities such as dermatitis were observed. Accordingly, 0.1 mg/kg dosed every three weeks was determined to be the maximum tolerated dose (MTD) of INBRX-106 in combination with Keytruda.
Out of five response evaluable patients with tumor types responsive to immunotherapy in the active dose range of INBRX-106 in combination with Keytruda, two durable partial responses were achieved in checkpoint inhibitor naïve nasopharyngeal carcinoma and uveal melanoma patients with duration greater than six months with treatment ongoing. Additionally, a third checkpoint inhibitor exposed cutaneous melanoma patient has a double-digit reduction in tumor volume and duration greater than four months with treatment ongoing.
Part 2, which was run in parallel with Part 3, is ongoing and aimed at investigating single agent INBRX-106 dosed at 0.03 mg/kg in two different dosing schedules in patients with tumor types responsive to checkpoint inhibitors. Four of ten response evaluable non-small cell lung cancer (NSCLC) and melanoma patients receiving INBRX-106 in either Part 1 or 2 of the trial have been on treatment with INBRX-106 for at least six months. Of those four patients, three had previous exposure to checkpoint inhibitors and the fourth, a uveal melanoma patient, was checkpoint inhibitor naïve. To date, the longest duration on treatment with single agent INBRX-106 is 90 weeks (approximately 21 months) and ongoing in a NSCLC patient refractory to Keytruda.
"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, CEO of Inhibrx. "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."
Part 4 (combination dose expansion) of the trial initiated in a NSCLC cohort and a basket cohort in patients who relapsed or were refractory to checkpoint inhibitors, as well as in selected checkpoint inhibitor naive patient cohorts including cutaneous melanoma, uveal melanoma, head and neck squamous cell carcinoma and nasopharyngeal carcinoma. We expect to have initial data from Part 4 of this trial late this year.
About INBRX-106
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. We engineered INBRX-106 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.
The trial for INBRX-106 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 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.
About the Inhibrx sdAb Platform
Inhibrx utilizes diverse methods of protein engineering in the construction of therapeutic candidates that can address the specific requirements of complex target and disease biology. A key tool for this effort is the Inhibrx proprietary sdAb platform, which enables the development of therapeutic candidates with attributes superior to other monoclonal antibody and fusion protein approaches. This platform allows the combination of multiple binding units in a single molecule, enabling the creation of therapeutic candidates with defined valency or multiple specificities, potentially capable of enhanced cell signaling or conditional activation. An additional benefit of this platform, these optimized and/or multi-functional entities can be manufactured using the established processes that are commonly used to produce therapeutic proteins.
Inhibrx is pursuing targets with early validation where other therapeutics have demonstrated liabilities as well as a portfolio of sdAb based therapeutic candidates in a variety of indications for novel targets.