Corbus Pharmaceuticals Targets HPV-Linked Head and Neck Cancer With CRB-701 Study

Key Points

• Corbus plans to start a registrational study of CRB-701 this summer in second-line oropharyngeal head and neck cancer, with a separate frontline combination study with pembrolizumab already underway. The company hopes to see early signs of efficacy from the combination trial next year.
• Panelists said HPV-associated oropharyngeal cancer is a distinct and growing patient population, with a meaningful recurrent or metastatic segment that could support the trial. They estimated the relevant U.S. second-line population may be roughly 7,500 to 10,000 patients.
• The discussion highlighted Nectin-4 as a validated target and said CRB-701 may have a tolerability edge versus other MMAE-based ADCs, though ocular toxicity remains the main side effect to manage. Panelists also said the upcoming study could show meaningful activity if response rates reach the 30% to 40% range, above typical post-immunotherapy chemotherapy outcomes.

Corbus Pharmaceuticals NASDAQ: CRBP executives and oncology specialists used an ASCO-linked discussion to outline the rationale for focusing the company’s CRB-701 program on recurrent or metastatic oropharyngeal head and neck cancer, particularly in patients whose disease is associated with human papillomavirus, or HPV.

The event was moderated by Yuval Cohen, Corbus’ CEO and director, and featured Ari Rosenberg, associate professor of medicine at the University of Chicago; Glenn Hanna, director of the CCTI Early Drug Development Project at Dana-Farber Cancer Institute; and Cesar Perez, director of the Drug Development Unit at Sarah Cannon Research Institute.

Cohen said Corbus plans to launch a registrational study of CRB-701 in the second-line monotherapy setting this summer. He also said another study is underway at the panelists’ centers evaluating CRB-701 in combination with pembrolizumab in the frontline setting, with the company hoping to see an early “flavor of efficacy” next year.

Oropharyngeal Cancer Seen as a Distinct Population

Rosenberg described oropharyngeal cancer as a subtype of head and neck squamous cell carcinoma that typically arises in the tonsil and base of tongue. He said HPV-associated oropharyngeal disease is biologically distinct from HPV-unrelated disease, which is often linked to smoking and alcohol use.

Hanna said identifying these patients is generally straightforward in clinical practice, noting that physicians can examine the oropharynx directly, use fiber-optic nasal endoscopy and test lymph node biopsies for HPV status. He also said HPV-associated oropharyngeal cancer is expected to remain a growing clinical issue for decades despite HPV vaccination efforts, because of low vaccine uptake and the long lead time between infection and cancer diagnosis.

“This is not going anywhere in our careers,” Hanna said.

Panelists said the epidemiology varies by geography. Perez noted that different regions within the United States can see different mixes of HPV-related and smoking-related disease. Hanna said HPV-positive oropharyngeal patients are common in Boston, while HPV positivity is lower in parts of Asia and smoking-related disease remains more common in some other regions.

Panelists Estimate a Meaningful Second-Line Population

The physicians said the number of patients with recurrent or metastatic oropharyngeal cancer is substantial and growing. Rosenberg said even among HPV-associated patients, who generally have better outcomes with definitive treatment, about 15% to 25% may develop recurrence, depending on the data set.

Hanna cited SEER data indicating roughly 43,000 to 45,000 head and neck cancer cases annually in the U.S. He estimated that the relevant recurrent metastatic oropharyngeal population could be in the range of 7,500 to 10,000 patients, potentially higher over time. He added that patients with HPV-positive recurrent disease are often fit and motivated to travel to academic centers for clinical trials after immunotherapy.

“The number one advanced patient referral is a second, third-line motivated HPV positive patient post-IO who says, ‘I’m not getting chemo. This is not going to work. What do you have for me?’” Hanna said.

Perez said HPV-related patients are more likely than HPV-unrelated patients to make it to first- and second-line recurrent metastatic therapy because they are often healthier and have fewer comorbidities.

EGFR Agents Viewed as Serving a Different Segment

The panel contrasted CRB-701’s target population with emerging EGFR bispecifics and related agents in head and neck cancer. Rosenberg said EGFR targeting appears to be more relevant for HPV-unrelated disease, and he cited the negative INTERLINK-1 study as part of the evidence supporting that view.

Hanna said several EGFR-focused development programs are either explicitly HPV-negative or appear more likely to serve HPV-negative populations. He said that leaves an unmet need for HPV-positive oropharyngeal patients in later lines of therapy.

Perez added that PD-L1-low patients represent another area of unmet need and said he has seen activity with CRB-701 in patients with PD-L1 of less than one, though the discussion did not provide detailed efficacy data.

Nectin-4 ADC Rationale and Toxicity Discussion

CRB-701 is a Nectin-4 antibody-drug conjugate armed with MMAE. Rosenberg said Nectin-4 expression is high in head and neck cancer and appears enriched in HPV-positive patients. He pointed to prior experience with enfortumab vedotin, marketed as PADCEV, as evidence that Nectin-4 is a relevant target in head and neck cancer, though he noted that enfortumab’s toxicity profile includes peripheral neuropathy driven by free MMAE.

Hanna said PADCEV has been “deprioritized” in head and neck cancer, based on what he described as public information, and said CRB-701 may have an opportunity in a space where Nectin-4 has already been validated.

Perez said CRB-701 differs from enfortumab vedotin, including having less free payload and a drug-antibody ratio of 2 rather than 4. He said that, in his experience treating roughly 34 or 35 patients with CRB-701, peripheral neuropathy has not been a significant issue and he has not seen the same hyperglycemia, liver abnormalities, rashes or severe neuropathy he has encountered with other MMAE-based ADCs.

The main toxicity discussed was ocular toxicity. Rosenberg said management has become “quite protocolized,” including baseline ophthalmology evaluation, patient education, eye-drop prophylaxis and treatment holds when symptoms arise. Hanna said ocular toxicity can sound concerning because it involves vision, but he emphasized that Grade 1 events are asymptomatic and Grade 2 events can include symptoms such as dry or irritated eyes. Perez said the events are reversible and that treatment holds, rather than discontinuation, have often been sufficient.

Trial Design and Comparator Expectations

In response to analyst questions, Hanna said focusing the registrational trial on oropharyngeal cancer rather than requiring HPV testing may avoid the need for a companion diagnostic, while still enriching for HPV-positive disease in the U.S., where he estimated 85% or more of oropharyngeal cancers are HPV-associated at major centers.

Asked what response rate would be compelling, Rosenberg said chemotherapy in the post-immunotherapy setting has response rates around 20% in head and neck cancer, and that 30% to 40% response rates would be meaningful. Perez said current second-line options are limited because many patients have already received platinum, taxanes and pembrolizumab in the frontline setting. Panelists generally said they would expect the comparator arm in the upcoming study to produce response rates around 15% to 20%.

Cohen said site selection for the registrational trial would likely emphasize North America and Western Europe, while avoiding regions with very high smoking prevalence when possible. Hanna said a largely U.S.-based population would be important, though some global involvement would also be appropriate.

About Corbus Pharmaceuticals NASDAQ: CRBP

Corbus Pharmaceuticals Holdings, Inc is a clinical-stage biopharmaceutical company dedicated to the development and commercialization of therapeutic candidates for rare, life-threatening inflammatory and fibrotic diseases. The company's lead investigational therapy, lenabasum, is a synthetic, oral cannabinoid receptor type 2 (CB2) agonist designed to resolve chronic inflammation by harnessing the body's innate resolution pathways. Corbus operates by advancing small-molecule compounds through preclinical and clinical studies to address unmet medical needs in autoimmune and inflammatory disorders.

Lenabasum is currently under evaluation in a Phase 3 clinical trial for diffuse cutaneous systemic sclerosis (dcSSc) and in a Phase 2 study for cystic fibrosis–related inflammation.

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