Micvotabart Pelidotin Monotherapy Yields Responses in Pretreated Recurrent/Metastatic HNSCC

Administration of the first-in-concept antibody-drug conjugate (ADC) micvotabart pelidotin (PYX-201) led to responses and consistent disease control in the second- or later-line treatment of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), according to updated data from the dose-expansion portion of an ongoing phase 1 monotherapy study (NCT05720117).¹

At a data cutoff of August 18, 2026, evaluable patients (n = 33) treated at a dose of 5.4 mg/kg every 3 weeks achieved a confirmed objective response rate (ORR) of 36% and a disease control rate (DCR) of 94%. Additionally, 75% of responders experienced a response by their first scan at 6 weeks, and 83% had a greater than 50% tumor reduction from baseline.

In the5.4-mg/kg dose cap group, the median progression-free survival (PFS) was 6.2 months (95% CI, 4.8-8.8), the 12-month overall survival (OS) probability was 79% (95% CI, 58.1%-90.3%), and the median OS had not been reached. Responses were observed across subgroups defined by HPV status and by prior EGFR inhibitor or taxane exposure.

Among safety-evaluable patients (n = 35), treatment-related adverse effects (TRAEs) occurred in 91.4% of patients, including grade 3 or higher TRAEs at a rate of 54.3%. Serious TRAEs and TRAEs leading to treatment discontinuation each occurred in 14.3% of patients, with no treatment-related deaths reported.

The most common payload-associated TRAEs of interest were cutaneous, peripheral neuropathy, and ocular toxicities. Pyxis reported no new safety signals and characterized the tolerability profile as consistent with prolonged auristatin exposure, adding that dose capping reduced the frequency and severity of AEs in patients with high body weight.

Pyxis Oncology, the developer of micvotabart pelidotin, plans to hold an end-of-phase 2 meeting with the FDA to align on dose selection in the first quarter of 2027 and expects to report updated OS data from the phase 1 monotherapy study in the first half of 2027. The company intends to initiate the phase 3 Headliner trial, a randomized, open-label study comparing micvotabart pelidotin with investigator's choice of therapy in the second- or third-line treatment of patients with recurrent/metastatic HNSCC in mid-2027.

Micvotabart pelidotin previously received FDA fast track designation for the treatment of adults with R/M HNSCC whose disease progressed following platinum-based chemotherapy and anti-PD-(L)1 therapy.

“These [monotherapy] results demonstrated rapid and deep responses, along with PFS and preliminary OS results that warrant further evaluation,” Alan L. Ho, MD, PhD, chief of the Head and Neck Oncology Service and an attending medical oncologist at Memorial Sloan Kettering Cancer Center in New York, stated in a news release.

How is the monotherapy trial of micvotabart pelidotin being conducted?

The first-in-human, open-label, multicenter phase 1 study is evaluating micvotabart pelidotin as a single agent in patients with advanced solid tumors and is enrolling an estimated 330 participants across a dose-escalation portion and dose-expansion cohorts in HNSCC, triple-negative breast cancer, hormone receptor–positive/HER2-negative breast cancer, and other solid tumor types.²

To be eligible, patients with HNSCC must have received 1 to 2 prior lines of therapy, including prior platinum-based chemotherapy and a PD-1/PD-L1 inhibitor. An ECOG performance status of 0 or 1 and measurable disease per RECIST 1.1 criteria are both required. Patients with prior EDB+FN-targeting treatment, symptomatic brain metastases, or grade 2 or higher neuropathy were excluded.

In the reported analysis, patients received micvotabart pelidotin at 5.4 mg/kg intravenously once every 3 weeks.

The primary end points are the incidence of dose-limiting toxicities and safety in the dose-escalation portion and ORR in the dose-expansion portion, with secondary end points including PFS, OS, duration of response, and DCR.

“We are particularly encouraged by the combination of rapid and deep responses, substantial survival outcomes and a manageable safety profile,” Tom Civik, chief executive officer and chairman of Pyxis Oncology, added in a news release.¹

References

1. Pyxis Oncology announces positive updated data from phase 1 monotherapy study of micvotabart pelidotin (Micvo) in second-line and beyond recurrent/metastatic head and neck squamous cell carcinoma (2L+ R/M HNSCC). News release. Pyxis Oncology, Inc. September 9, 2026. Accessed September 9, 2026. https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-positive-updated-data-phase-1
2. A study of PYX-201 in advanced solid tumors. ClinicalTrials.gov. Updated June 30, 2026. Accessed September 9, 2026. https://clinicaltrials.gov/study/NCT05720117