The phase 1/2 KEYMAKER-U02 trial evaluating pembrolizumab alone or as a combination therapy in stage IIIB-D melanoma found no adverse event–related deaths.
The phase 1/2 KEYMAKER-U02 trial evaluating pembrolizumab alone or as a combination therapy in stage IIIB-D melanoma found no adverse event–related deaths.
Neoadjuvant pembrolizumab (Keytruda) alone or as a combination therapy with vibostolimab (MK-7684) or gebasaxturev (coxsackievirus A21), followed by adjuvant pembrolizumab, displayed manageable safety in patients with stage IIIB-D melanoma, according to results from the phase 1/2 KEYMAKER-U02 trial (NCT04303169) published in Nature Medicine.1
Safety data from the trial revealed that across all arms (n = 66), 63 patients (95%) had at least 1 adverse event (AE), including 96% of the pembrolizumab/vibostolimab arm, 96% of the pembrolizumab/gebasaxturev arm, and 93% of the monotherapy arm. Furthermore, at least 1 grade 3 or 4 AE occurred in 15%, 40%, and 27% of respective arms, and no deaths related to an AE occurred.
Treatment-related AEs (TRAEs) occurred in 92% of the pembrolizumab/vibostolimab arm, 84% of the pembrolizumab/gebasaxturev arm, and 80% of the monotherapy arm. Additionally, grade 3 or 4 TRAE occurrence was reported in 8%, 28%, and 7% of each respective arm.Any-grade TRAEs occurring in more than 20% of patients included pruritus (46%), fatigue (38%), and vitiligo (27%) with pembrolizumab/vibostolimab; pruritus (40%), fatigue (28%), asthenia (24%), injection site pain (20%), and vitiligo (20%) with pembrolizumab/gebasaxturev; and pruritus (33%), arthralgia (27%), decreased blood creatinine phosphokinase (20%), and fatigue (20%) with pembrolizumab monotherapy.
“[N]eoadjuvant therapy with pembrolizumab plus vibostolimab, pembrolizumab plus gebasaxturev or pembrolizumab monotherapy followed by surgery and adjuvant pembrolizumab had manageable safety in patients with stage IIIB–D melanoma,” Reinhard Dummer, MD, professor in the Department of Dermatology at the University of Zurich and vice chairman of the Department of Dermatology in the University Hospital of Zurich, wrote in the publication with study coinvestigators.1 “The efficacy observed in the combination arms was similar to that in the pembrolizumab monotherapy arm. Longer follow-up will provide further insight into whether there is an incremental benefit in combining neoadjuvant pembrolizumab with other therapies.”
Sixty-six patients with stage IIIB-D melanoma were randomly assigned 1:1:1 to receive either pembrolizumab plus vibostolimab (n = 26), pembrolizumab plus gebasaxturev (n = 25), or pembrolizumab monotherapy (n = 15). After the monotherapy arm enrolled 15 patients, the remaining patients were randomly assigned to receive either combination regimen. In each respective arm, 25, 23, and 14 patients completed neoadjuvant therapy, and 20, 19, and 11 received adjuvant therapy following surgery.
The neoadjuvant regimen comprised 200 mg of intravenous pembrolizumab every 3 weeks for up to 2 administrations plus 200 mg of intravenous vibostolimab every 3 weeks for up to 2 administrations in arm 1, 400 mg of intravenous pembrolizumab for 1 administration plus gebasaxturev at 3 x 108 tissue culture infectious dose 50% by intratumoral injection for up to 5 administrations in arm 2, and 400 mg of intravenous pembrolizumab for 1 administration in arm 3.
All patients underwent surgical resection following 6 weeks of initial neoadjuvant dosing. Adjuvant therapy consisted of 400 mg of intravenous pembrolizumab every 6 weeks for up to 8 cycles or until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision.
The primary end points were AE incidence, discontinuation due to AEs, and pathological complete response (pCR rate).2 Secondary end points included near pCR rate, pathological partial response (pPR) rate, and recurrence-free survival.
The pCR rate was 38% (95% CI, 20%-59%) in the pembrolizumab/vibostolimab arm, 28% (95% CI, 12%-49%) in the pembrolizumab/gebasaxturev arm, and 40% (95% CI, 16%-68%), in the monotherapy arm. Additionally, major pathologic responses, which accounts for pCR and near pCR, occurred in 50%, 40%, and 47% of the respective arms, and pPRs occurred in 31%, 12%, and 27%, respectively.