Inhibrx（INBX.US）OX40 激动剂 INBRX-106 头颈鳞癌二期 HexAgon 更新数据：cORR 48.3% vs Keytruda 单药 26.5%、中位 PFS 9.6 vs 4.9 个月、HPV+ 亚组 cORR 80%，拟新增 50 例 HPV+ 患者博加速审批——该数据 9 月 8 日盘前已由公司新闻稿首发，本条为 5 天前的 CEO 访谈复述，市场已完整反应且方向为下跌

Inhibrx Biosciences’ CEO has argued that the 9.6 months of progression-free survival (PFS) demonstrated by its OX40 agonist in a phase 2 study has proven the therapy’s durability in treating head and neck cancer.
The San Diego-based biotech has been evaluating INBRX-106 in the phase 2 HexAgon study of 68 people with treatment-naïve, metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC). These patients, all of whom had high PD-L1 expression, received Merck & Co.’s Keytruda as a monotherapy or with Inhibrx’s hexavalent OX40 agonist INBRX-106.
An interim analysis back in May tied the combo treatment to an objective response rate (ORR) of 44%, compared with 21.4% for the Keytruda-only cohort. An updated look at the data after an Aug. 19 cutoff continued to show that the combo treatment nearly doubled the ORR over Keytruda monotherapy, with the updated rates now standing at 48.3% and 26.5%, respectively.
The ORR result met the study’s primary endpoint, Inhibrx confirmed to Fierce this morning.
While the May readout had been too early to give a sense of the PFS benefit, Inhibrx said this morning that median PFS was 9.6 months, compared with 4.9 months for Keytruda alone. Six-month PFS rates were 72.4% and 42.8%, respectively, the biotech noted.
The company claimed the data made INBRX-106 the “first OX40 agonist to demonstrate clinical benefit in a randomized study.”
“The biggest difference in this dataset compared with May's dataset is maturity,” Inhibrx CEO Mark Lappe told Fierce.
“In May, we didn't have [six-month PFS data] yet—we could see where it was going but the data hadn't matured,” Lappe added. “The dataset is still not fully matured but at 9.6 months PFS, there is no question about the drug’s durability.”
Another key update is that Inhibrx has been able to break up the trial population by HPV status. Specifically, patients with HPV+ disease who received the combo treatment demonstrated an 80% ORR, compared with 33.3% who received Keytruda alone.
Median PFS in the combination arm among patients with HPV+ disease had not yet been reached at the time of the August cutoff, the company noted.
The HPV+ results have prompted the biotech to expand the study by adding 50 patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC), with the goal of supporting a potential accelerated approval pathway.
Lappe said drilling down into the HPV subgroup “supports our hypothesis that while we are clearly seeing a benefit in the negative population over Keytruda, the HPV+ population represents a highly immunogenic tumor.”
“When those antigens are present, OX40 costimulation can come in and really amplify that response,” the CEO added.
Lappe suggested that the HPV+ dataset is “so profound” that the FDA could potentially award breakthrough therapy designation and accelerated approval for phase 2 data “since our trial is already a randomized head-to-head against the standard of care.”
“By adding an additional 50 HPV+ patients, we think the signal will be strong enough for the FDA to consider this,” the CEO said.
Following the phase 2 expansion, the company plans to work with the FDA before initiating the phase 3 portion of the HexAgon trial, which the biotech hopes could potentially serve as the confirmatory study.
Despite OX40’s potential, the target has long vexed the industry, with companies including Amgen and AstraZeneca struggling to translate promising early data into the clinic. Inhibrx identified the bivalent design of earlier OX40 agonists as a potential cause of the failures, leading to its hexavalent candidate.
“The previous generation of OX40 agonists were conventional bivalent antibodies, but OX40 depends on higher-order clustering to generate a strong costimulatory signal,” Lappe noted. “A bivalent antibody can engage the receptor, but it does not efficiently bring enough OX40 molecules together to produce the level of signaling required for robust T-cell activation.”
Beyond the trial expansion into HPV+ patients, Lappe said he sees potential for the candidate in other populations. Inhibrx plans to conduct a phase 1/2 study of INBRX-106 in the perioperative setting of non-small cell lung cancer (NSCLC), with initial results targeted for mid-2027. The study is intended to explore the potential of the drug in broader indications.
“We believe INBRX-106 can expand into not only other highly immunogenic tumors like lung [and] melanoma, but we also believe we can synergize very well with cancer vaccines where the vaccine can prime a tumor-specific T-cell response, and INBRX-106 could come in and expand it,” Lappe explained. “HPV+ patients are just the beginning for this drug.”
The latest data have made Lappe bullish on the drug’s potential and hinted that the company could be open to a deal if the price is right. Reuters reported earlier this year that Merck, Germany’s Merck KGaA and Japan’s Ono Pharmaceutical had all shown interest in INBRX-106.
“We are the only ones with an OX40 agonist, a target that many pharmaceutical companies have been trying to drug for several years,” Lappe told Fierce. “With the potential for the market to be as expansive as we believe it could be, I think it’s a good guess there would be many parties interested in owning this drug.”
Inhibrx is no stranger to the M&A cycle. Before Sanofi completed its $1.7 billion acquisition of the biotech’s predecessor in 2024 to get its hands on the alpha-1 antitrypsin deficiency candidate INBRX-101, Inhibrx spun out the current Inhibrx Biosciences to take forward INBRX-106 and other assets.
“I’m not sure what the future holds for the company, but we are excited to be part of this journey of potentially changing the paradigm of oncology treatment and what that means for patients to come,” Lappe said.