At ESMO, 39% Response Rate Seen for EV Plus Pembro in Recurrent Head and Neck Squamous Cell Carcinoma

Patients with recurrent or metastatic squamous cell carcinoma (HNSCC), who had markers showing they would likely respond to certain types of immunotherapy, had an overall response rate of 39% within a study that combined enfortumab vedotin (Padcev; Astellas/Pfizer) with pembrolizumab (Merck) to treat several types of cancer.¹

The cohort analysis of the phase 2 EV-202 trial (NCT04225117), presented Sunday during the 50th Congress of the European Society of Medical Oncology (ESMO), is the latest set of results involving the combination of enfortumab vedotin (EV), the nectin-4 directed antibody drug conjugate (ADC), and pembrolizumab, which has produced banner results in bladder cancer² but fallen short in other types, such as non-small cell lung cancer (NSCLC).³

In their abstract, authors led by Paul Swiecicki, MD, associate professor, Division of Hematology/Oncology, University of Michigan, explained that patients with recurrent or metastatic HNSCC have a poor prognosis. This is an area of unmet need, as these patients have already received other treatments, and new options are needed for treatments attempted at this stage. The patients in this cohort all had a PD-L1 combined positive score (CPS) of at least 1, indicating a better chance of success with pembrolizumab than patients without this score.

The 41 patients in this cohort received enfortumab vedotin at 1.25 mg/kg intravenously on days 1 and 8 plus pembrolizumab at 200 mg intravenously on day 1 of each 21-day cycle. Patients were treated until disease progression, unacceptable toxicity, or completion of the maximum number of cycles outlined in the study protocol.

The primary end point was investigator-assessed confirmed objective response rate (ORR) per RECIST 1.1 criteria. Secondary end points included duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS), all assessed by investigators per RECIST 1.1 criteria, along with overall survival (OS) and safety.

The patients enrolled had a median age of 67 years; 76% were male, and 27% had HPV+ disease. For PD-L1 CPS status, 39% had a score of 1-19 and 60% had a score of 20 or higher.

Results were as follows:

• Evaluable patients achieved an investigator-assessed ORR of 39.0% (95% CI, 24.2%-55.5). The complete response (CR) rate was 9.8%, and the partial response (PR) rate was 29.3%.
• Patients had best response of stable disease (36.6%), progressive disease (17.1%), or were not evaluable for response (7.3%).
• DCR was 75.6% (95% CI, 59.7%-87.6%), and median PFS was 5.1 months (95% CI, 3.5-not evaluable). Median OS had not been reached at the time of data cutoff in February 2025; follow-up is ongoing.

A total of 41 patients were enrolled in this cohort of the EV-202 trial. At the data cutoff date, 11 patients remained on treatment with enfortumab vedotin plus pembrolizumab, and 2 patients continued on enfortumab vedotin monotherapy.

The median relative dose intensity (RDI) for enfortumab vedotin was 89.0% (range, 42.1%–100.2%). Patients received a median of 6.0 cycles (range, 1-17) of enfortumab vedotin and a median of 6.0 cycles (range, 1-21) of pembrolizumab. The median duration of treatment for both agents was 4.9 months, ranging from 0.7 to 13.6 months for enfortumab vedotin and 0.7 to 15.4 months for pembrolizumab.

Safety data showed that 92.7% of patients experienced a treatment-related adverse event (TRAE) and 70.7% had a TRAE of grade 3 or higher; common grade 3 events were fatigue, acute respiratory failure, dehydration, dysphagia, and maculopapular rash.

References

1. Swiecicki PL, Hanna GJ, Geiger JL, et al. Enfortumab vedotin plus pembrolizumab as first-line treatment in recurrent or metastatic head and neck squamous cell carcinoma: results from a cohort of the EV-202 trial. Presented at: 50th Congress of the European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Presentation 1329MO.

2. Vulsteke C, Kaimakliotis H, Danchaivijitr P, et al. Perioperative (periop) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin ineligible: the phase III KEYNOTE-905 study. Presented at: 50th European Society for Medical Oncology Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA2.

3. Muro K, Feinstein T, Baranda J, et al. Enfortumab vedotin in patients with advanced non-small cell lung cancer after disease progression on platinum- and PD-1/PD-L1 inhibitor-containing regimens: Phase 2 international multicenter EV-202 study. Eur J Cancer. 2025;227;115603. DOI: 10.1016/j.ejca.2025.115603