Enfortumab Vedotin Elicits Compelling Data in Head and Neck Cancer


Patients with heavily pretreated head and neck cancer achieved an overall response rate of 24% with enfortumab vedotin in the phase 2 EV-202 study.

Jessica Geiger, MD

Jessica Geiger, MD

Antitumor activity, tolerability, and a manageable safety profile were observed with enfortumab vedotin (Padcev) monotherapy among patients with heavily pretreated head and neck cancer (HNC) in the phase 2 EV-202 study (NCT04225117).1

With a median follow-up of 9.33 months, the overall response rate (ORR) was 23.9% (n = 11; 95% CI, 12.6-38.8) and the disease control rate (DCR) was 56.5% (n = 26; 95% CI, 41.1-71.1) among this patient population when treated with enfortumab vedotin.

Regarding safety, adverse events (AEs) commonly observed among patients included fatigue, alopecia, and peripheral sensory neuropathy (28.3% for each; n = 13). AEs deemed grade ≥3 occurring in > 1 patient were anemia (n = 3), decreased neutrophil count (n = 2), and malignant neoplasm progression (n = 2).

“This is a very heavily pretreated head and neck cancer population and to achieve an overall response rate of 24% is significant. This is compelling and great data that represents a novel agent that could have great success and clinical meaningfulness in our patients with recurrent or metastatic head and neck cancer,” Jessica Geiger, MD, Cleveland Clinic, told Targeted OncologyTM.

Enfortumab vedotin is a Nectin-4 directed antibody drug conjugate (ADC) that has been granted approval for treatment of adults with locally advanced or metastatic urothelial carcinoma that has been previously treated with platinum-containing chemotherapy and a PD-1/L1 inhibitor. This approval was based on findings from the phase 3 EV-301 trial which showed a survival benefit among patients treated with enfortumab vedotin.2

“Recurrent metastatic head and neck cancer represents an unmet medical need in oncology treatment and the need for clinical trials and novel therapeutics. For patients who don’t respond or fail to respond to immunotherapy, these patients have very limited treatment options. This study is looking at second- or beyond lines of therapy,” added Geiger.

In the multicohort, open-label phase 2 EV-202 study, patients with previously treated locally advanced or metastatic solid tumors were enrolled if their disease was not amenable to curative-intent treatment.1 Enrollment in the study was open to patients with an ECOG performance status of 0 or 1 with progression/relapse on platinum. In the HNC cohort, patients were required to have progressed/relapsed/discontinued treatment for toxicity after 1 platinum-based therapy for their disease. These patients must also have had no more than 2 lines of cytotoxic therapy in the locally advanced or metastatic setting.

Once enrolled, patients were treated with enfortumab vedotin at a dose of 1.25 mg/kg via intravenous infusion on days 1, 8, and 15 of a 28-day cycle until disease progression or discontinuation.

The primary end point of the study was confirmed ORR per RECIST v1.1 and per investigator assessment. Investigators also evaluated the secondary end points of duration of response (DOR), DCR, progression-free survival (PFS), overall survival (OS), and safety/tolerability.

A total of 44 patients were enrolled into the HNC cohort of the study as of April 11, 2022. The median age of patients enrolled was 65 years, 87% of patients were men, and the majority had received ≥2 lines of systemic therapy in the metastatic setting. Histology at diagnosis was squamous cell carcinoma for 45 (97.8%) pts and “other” for 1 pt.

The median DOR was not reached among patients enrolled in the HNC cohort and the median time to response was 1.74 months. Additionally, the median progression-free survival rate was 3.94 months and OS was 5.98 months, respectively.

Aside from the promising efficacy data, treatment-related AEs of special interest for enfortumab vedotin included skin reactions which occurred in 45.7% of patients, peripheral neuropathy in 32.6%, and hyperglycemia in 4.3%.

Overall, these findings show that treatment with enfortumab vedotin has encouraging activity in patients with previously treated HNSCC after PD-1 inhibitor failure. With these findings, further investigation of enfortumab vedotin and its activity in patients with HNC is warranted.

“Our next steps are [seeing if we] can bring this drug into earlier treatment in recurrent/metastatic cancer. We are looking to design a study adding this to pembrolizumab [Keytruda] or immunotherapy in an earlier setting. Comparing it in a phase 3 randomized study in heavily pretreated patients may be on the horizon as well. We are looking to identify the patients who would benefit most from this, and then expand on it in a clinical trial,” concluded Greiger.

  1. Swiecicki P, Yilmaz E, Rosenberg AJ, et al. Enfortumab vedotin in the previously treated advanced head and neck cancer (HNC) cohort of EV-202. J Clin Oncol. 2023;41(16):6017. doi:10.1200/JCO.2023
  2. FDA grants accelerated approval to enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial carcinoma. FDA.gov. Accessed September 7, 2023. https://tinyurl.com/mwvty9a2

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