Nivolumab

Corbus Pharmaceuticals (Nasdaq: CRBP) announced that the FDA has aligned with its proposed registrational study designs for CRB-701, a Nectin-4–targeting antibody-drug conjugate (ADC), in second-line head and neck squamous cell carcinoma and cervical cancer, clearing the path toward randomized trials with objective response rate as the primary endpoint for potential accelerated approval. The ongoing Phase I/II study (NCT06265727) is a recruiting, open-label trial enrolling patients with Nectin-4–expressing advanced solid tumors. No patient numbers, dosing, or efficacy data are disclosed in this announcement; updated monotherapy results are scheduled for presentation at the 2026 ASCO Annual Meeting, May 29–June 2 in Chicago. The agreed registrational designs call for two separate randomized controlled studies. In second-line HNSCC, CRB-701 will be compared with physician’s choice chemotherapy, with ORR as the primary endpoint for accelerated approval and overall survival anchoring potential full approval. In cervical cancer, the comparator arm broadens to include physician’s choice chemotherapy or Tivdak (tisotumab vedotin), under the same dual-endpoint framework. Corbus said it expects to initiate the HNSCC registrational study in mid-2026; protocols and statistical analysis plans for both studies remain under finalization with the FDA. No efficacy numbers from the Phase I/II program were released alongside this regulatory update. About CRB-701 CRB-701 is an ADC licensed from China-based CSPC Megalith Biopharmaceutical in 2023 that pairs a Nectin-4–directed antibody with a site-specific, cleavable linker and a homogeneous drug-to-antibody ratio of 2, using monomethyl auristatin E as the cytotoxic payload. The low DAR and site-specific conjugation are designed to reduce free MMAE systemic exposure relative to enfortumab vedotin (Padcev), the approved Nectin-4 ADC whose indication is currently limited to urothelial carcinoma. Whether that structural distinction translates into a differentiated clinical safety profile in HNSCC or cervical cancer remains to be established in the registrational program. The FDA has granted CRB-701 Fast Track designation in both indications. In the second-line HNSCC setting, the approved landscape consists primarily of anti-PD-1 agents — pembrolizumab and nivolumab — along with cetuximab and cytotoxic chemotherapy. With checkpoint inhibitors now embedded in first-line regimens, a growing proportion of patients entering second-line treatment have already progressed on immunotherapy, a population for which no approved targeted option exists. Nectin-4 expression is independent of PD-L1 status, which is the mechanistic basis for CRB-701’s potential activity in this post-IO population, though that hypothesis requires prospective validation. In cervical cancer, tisotumab vedotin received full FDA approval in April 2024 on the strength of overall survival data from the innovaTV 301 Phase III trial, making it the only approved ADC in this setting and the named comparator in Corbus’s registrational design. Tivdak targets tissue factor rather than Nectin-4 and carries a known ocular toxicity burden, including conjunctivitis and keratitis, that has prompted post-marketing monitoring studies. Cross-trial comparisons are limited by differences in patient populations, prior therapy, and trial design, so any inference about how CRB-701’s DAR-2 construct might compare on tolerability remains speculative until head-to-head or at least contemporaneous data are available. The company also disclosed plans to report combination data for CRB-701 plus pembrolizumab (Keytruda) in first-line HNSCC patients in Q4 2026, which could inform whether a broader registration strategy is warranted beyond the second-line setting. Separately, Corbus announced that Chief Medical Officer Dominic Smethurst will step down on June 30, 2026. The company said it plans to add senior leaders in preparation for the registrational phase. Updated CRB-701 monotherapy data, including response durability and HNSCC subgroup analyses, will be presented at ASCO 2026. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

iStock, Talaj The upcoming FDA decision for Replimune’s advanced melanoma drug could be a litmus test for the agency’s future regulatory decision-making, analysts say, with implications stretching well beyond one company. Last month, the FDA revealed that embattled Center for Biologics Evaluation and Research chief Vinay Prasad would step down from his role at the end of April. This is just the latest in an unprecedented streak of agency departures during the past year, including that of long-time chief cancer regulator and short-term Center for Drug Evaluation and Research head Richard Pazdur . Both men were thought to have played a part in the rejection of Replimune’s advanced melanoma drug candidate. This week, that asset will get another chance. While Replimune and the advanced melanoma community wait at the edge of their seats for the FDA’s decision on the drug, called RP1, the outcome could affect the biopharma industry more broadly. The agency’s action on this filing is being regarded as a barometer of the FDA’s regulatory decision-making, Cantor Fitzgerald analyst Li Watsek told BioSpace . “I think a lot of folks are looking at Replimune’s PDUFA date as a first indicator of how the FDA is going to act going forward,” Watsek told BioSpace . “There’s a lot of chatter about political pressure and the way that FDA leadership has handled approvals.” Last July, Replimune, which is developing novel oncolytic immunotherapies for difficult-to-treat cancers, was hit with an unexpected complete response letter (CRL) for RP1. Two weeks later, it was revealed that Pazdur had objected to its approval, overruling the overall consensus at CBER. Prasad—whom analysts originally suspected to be behind the rejection—ultimately deferred to Pazdur. Last October, following protests from researchers on RP1’s trials, the FDA accepted Replimune’s resubmitted biologics license application for the drug. Replimune is not alone in being stymied by intervention from senior FDA leaders. Prasad reportedly played a role in rejections for Capricor Therapeutics’ Duchenne muscular dystrophy cardiomyopathy drug deramiocel , also in July 2025, and more recently for Disc Medicine’s rare blood disease drug bitopertin . FDA FDA Reversals Send UniQure, Biohaven, Capricor, More Into a ‘Tailspin’ Since July, several biotechs have been forced to pivot as previous agreements with the FDA around evidence required for approval were reversed, a phenomenon that, according to experts, could portend a more restrictive regulator. November 24, 2025 · 7 min read · Heather McKenzie Read more A Surprise CRL RP1’s initial rejection was controversial because the therapy was fully expected to be approved, according to Robert Driscoll, senior vice president of equity research at Wedbush Securities. It came as a surprise to Replimune CEO Sushil Patel who noted in a statement at the time that the issues highlighted in the CRL were not raised by the FDA during mid- and late-cycle reviews. The drug, in combination with Bristol Myers Squibb’s PD-1 blockbuster Opdivo led to a 32.9% overall response rate, with a complete response rate of 15% in the Phase 2 IGNYTE trial , meeting its primary endpoint. The overall data were “very convincing,” Driscoll told BioSpace , adding that previous studies indicated a significantly lower response rate of just 6–7% for PD-1s alone in the same patient population. However, the FDA suggested in the CRL that the higher response rate could not be adequately interpreted due to the heterogeneity of the trial patient population. The agency attributed this to varying types of prior therapy received by patients and duration of treatment, among other factors. Two weeks after the rejection, 22 experts involved in the design and execution of IGNYTE penned an open letter in which they contended that that such heterogeneity was representative of a real-world treatment scenario. To address this objection, Replimune would need to run a control arm with Opdivo monotherapy, they said. However, this would be “impractical, unacceptable and borders on the unethical.” While advocacy for a certain treatment is not unheard of in the rare disease space, Watsek said the open letter and strong support for RP1 is “quite remarkable.” It is particularly uncommon for physicians in oncology to take such action, she added. Given all these factors, the initial rejection appears to be due to the decision-making of either Pazdur or Prasad, either alone or in combination, Driscoll said, and possibly related to the regulators’ objections to single-arm studies that do not include a control. A 50-50 Shot at Approval Replimune has a lot riding on the upcoming decision, slated to be delivered by April 10. RP1 is the company’s lead asset and, if approved, could generate peak sales of $800 million annually, according to Watsek. If RP1 is not approved, the company has indicated it may discontinue development of the asset and focus on other pipeline treatments, Driscoll added. Replimune would then need to raise enough capital to advance other assets through the clinic, he said. A type A meeting with the FDA in September 2025 failed to yield a clear path forward for RP1, according to the biotech. A month later, however, Replimune resubmitted its application. The company did not reveal what prompted this change; nevertheless, Replimune stated in a press release that the FDA indicated that it considered the resubmission to be “a complete response” to the CRL. With the uncertainty around the FDA, that won’t give investors a lot of comfort that this is going to be a slam dunk. Li Watsek, analyst at Cantor Fitzgerald As such, analyst sentiment around the reapplication is reasonably positive, Driscoll noted. Over the past few months, Replimune’s stock has been trading between $7 and $9, down from the highs of $12 prior to the rejection last July but substantially higher than the $3 it fell to on the release of the news. This reflects the idea that RP1 has a 50-50 shot at approval, Driscoll said. Wedbush views the odds more favorably than the broader market, as Driscoll predicted a 60–70% likelihood of success. Looking to a ‘Post-Prasad’ Future The imminent departure of Prasad—as well as the previous resignation of Pazdur—has heightened expectations for RP1’s approval, Watsek said, as both figures have been presumed to be involved in the “opposition” to the drug. Despite this, there is a lot of uncertainty over how the FDA will operate “post-Prasad,” she said. In addition, Prasad will remain head of CBER until the end of April, though it is unknown how active he will be, Watsek added. “Even though there are good reasons to be hopeful, with the physician group having played a pretty visible and vocal role in protesting the CRL decision, there is still a lot of bearish sentiment,” she continued. “With the uncertainty around the FDA, that won’t give investors a lot of comfort that this is going to be a slam dunk.” More broadly, Driscoll said, the biotech industry needs someone who is able to “steady the ship” to step into Prasad’s soon-to-be-vacated leadership position. “We need someone to come in that allows biotechs to be more confident in how regulatory decisions are being made,” he said. “Regulatory decisions affect years of drug development and trial design, so we’d love to see some stability.” Editorial Prasad’s Request To Remain Anonymous Shines Light on FDA’s Transparency Problem While requests by government officials for anonymity when speaking to the media are nothing new, the practice attracts more scrutiny when the Department for Health and Human Services has pledged a commitment to “radical transparency.” March 13, 2026 · 7 min read · Heather McKenzie Read more