Adding Inhibrx Biosciences’ OX40 agonist to Keytruda doubled the response rate in a midphase clinical trial, encouraging the biotech to advance a program that reportedly attracted the interest of Merck & Co.
San Diego-based Inhibrx generated the objective response rate (ORR) data in the phase 2 portion of its HexAgon study, which randomized 68 people with treatment-naïve, metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC). Patients, all of whom had high PD-L1 expression with combined positive score (CPS) of at least 20, took Merck’s Keytruda as a monotherapy or with Inhibrx’s hexavalent OX40 agonist INBRX-106.
The ORR in the combination cohort was 44% at an interim analysis, compared to 21.4% in the Keytruda control cohort. The control group ORR is in line with the result from Merck’s phase 3 trial, which linked Keytruda to a 23.3% response rate in a similar population of HNSCC patients with high PD-L1 expression.
The biotech expects to share progression-free survival data in the fourth quarter.
Inhibrx modeled its trial design on Merck’s study, focusing on patients with high PD-L1 expression to try to generate a clear signal that INBRX-106 adds to Keytruda’s efficacy. The ORR data, which included three complete responses on INBRX-106 and none in the control arm, provided enough of a signal for Inhibrx to expand its R&D program.
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“We believe we don’t just have more responders, but better responders, with the majority of responders in the combination arm exceeding 50% in tumor shrinkage [and] with three patients achieving complete response so far,” Inhibrx CEO Mark Lappe said on a call with analysts to discuss the data Monday. “If I’m a patient, it’s clear from the depth of response data which arm of the study I’d want to be in.”
The biotech plans to start the phase 3 part of the HexAgon trial in the third quarter. In parallel, Inhibrx will expand into more indications, with a trial in the perioperative setting in non-small cell lung cancer (NSCLC) next on its roadmap. The company plans to start studies in front-line metastatic NSCLC next year, and has identified opportunities to combine INBRX-106 with vaccines, T-cell engagers and CAR-Ts.
The R&D roadmap reflects Inhibrx’s belief that OX40 agonism holds the most promise in earlier-stage patients with more active and responsive immune systems. Multiple companies have tried to find a place for OX40 agonists in oncology treatment pathways, reflecting evidence that the mechanism drives T-cell expansion and other effects that could enhance the effects of checkpoint inhibitors.
Companies including AstraZeneca, Bristol Myers Squibb, GSK, Pfizer and Roche struggled to translate the preclinical promise into clinical efficacy, making OX40 part of a series of mechanisms that underwhelmed after being hyped as the key to unlocking the full power of PD-1/L1 drugs. Inhibrx identified the bivalent design of earlier OX40 agonists as a potential cause of the failures, leading to its hexavalent candidate.
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Evidence that Inhibrx has cracked the OX40 conundrum could further takeover talks. Last month, Reuters reported that Merck, Merck KGaA and Ono Pharmaceutical had shown an interest in INBRX-106. While Inhibrx has a sub-$2 billion market cap even after a recent surge, Reuters reported that Inhibrx’s pipeline could be worth $9 billion to buyers depending on the clinical trial data.
The deal “would be a strategic fit as Merck attempts to solve for approaching revenue declines,” BMO Capital Markets analysts said in a note to investors last month. If Merck bought Inhibrx and physicians favored INBRX-106 combinations over single-agent Keytruda, the Big Pharma could limit the impact of biosimilars that threaten to erode its cornerstone product in the coming years, the analysts said.
