medwireNews: Combining enfortumab vedotin with pembrolizumab could be a promising option for the first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer, indicates the EV-103 trial.
As reported at the ESMO Congress 2019 in Barcelona, Spain, treatment with the combination led to an objective response rate of 71%, with complete responses in 13% of patients and partial responses in 58%.
Presenting author Christopher Hoimes (Case Western Reserve University, Cleveland, Ohio, USA) highlighted that 93% of patients derived at least some benefit in terms of tumor shrinkage.
The median time to response was 2.0 months, and responses lasted from 1.0 to 10.5 months, with 22 of the 32 responders continuing study treatment at data cutoff.
Hoimes explained that enfortumab vedotin is an antibody–drug conjugate targeting Nectin-4 that has shown promising efficacy as a single agent in patients who have received prior treatment with platinum-based chemotherapy and immunotherapy.
These data led the investigators to assess enfortumab vedotin earlier in the treatment paradigm in combination with pembrolizumab and/or chemotherapy.
The current report focused on 45 individuals treated with enfortumab vedotin 1.25 mg/kg on days 1 and 8 of each 3-week cycle plus pembrolizumab 200 mg every 3 weeks in the dose escalation and dose expansion phase of the phase Ib study.
The presenter commented that the toxicity profile appeared “manageable and tolerable.” Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 51%, with lipase elevations, fatigue, and maculopapular rash the most frequent events, at rates of 13%, 9%, and 7%, respectively.
Immune-mediated AEs of at least grade 3 were observed in 11% of patients, one case each of grade 3 pneumonitis, bullous dermatitis, lipase elevation, and tubuleinterstitial nephritis, and one case of grade 4 myasthenia gravis.
Sixteen percent of participants had a serious TRAE, 9% discontinued study drugs due to TRAEs, most commonly as a result of peripheral sensory neuropathy, and one death was considered related to treatment.
Hoimes concluded that the combination “has the potential to become a platinum-free option” for treatment-naïve, cisplatin-ineligible, locally advanced or metastatic urothelial cancer patients, a population with a “high unmet need for effective and tolerable therapies.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group