Merck announced the European Commission (EC) has approved KEYTRUDA® (pembrolizumab), Merck?s anti-PD-1 therapy, in combination with Padcev® (enfortumab vedotin-ejfv), as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment for adults with resectable muscle-invasive bladder cancer (MIBC). This approval, which also covers KEYTRUDA SC® [known as KEYTRUDA QLEXTM (pembrolizumab and berahyaluronidase alfa-pmph) in the U.S.], marks the first and only PD-1 inhibitor plus antibody-drug conjugate (ADC) regimen available for patients with MIBC regardless of cisplatin eligibility in the European Union (EU). The EC approval is based on results from the Phase 3 KEYNOTE-B15 trial (also known as EV-304), which was conducted in collaboration with Pfizer and Astellas.
In the study, KEYTRUDA plus Padcev, as perioperative treatment, demonstrated a statistically significant improvement in event-free survival (EFS), reducing the risk of EFS events (defined as disease progression, recurrence or death) by 47% (HR=0.53 [95% CI, 0.41-0.70]). The major efficacy outcome measure was EFS as assessed by blinded independent central review (BICR), defined as the time from randomization to the first occurrence of the following events: disease progression preventing curative surgery, failure to undergo surgery for participants with muscle invasive residual disease, incomplete surgical resection, local or distant recurrence after surgery or death. Additional efficacy outcome measures were OS and pCR rate as assessed by blinded independent pathology review.
KEYTRUDA and KEYTRUDA QLEX are each indicated, in combination with enfortumab vedotin-ejfv, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment for the treatment of adult patients with muscle invasive bladder cancer (MIBC). In KEYNOTE-B15, the most common adverse reactions (=20%) occurring in cisplatin-eligible patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin-ejfv (n=403) were rash (63%), fatigue (48%), pruritus (46%), peripheral neuropathy (43%), diarrhea (36%), alopecia (32%), decreased appetite (29%), nausea and dysgeusia (28% each), constipation (27%), urinary tract infection (UTI) and dry eye (25% each), weight loss (22%), and hyperglycemia (20%). In KEYNOTE-905, the most common adverse reactions (=20%) occurring in cisplatin-ineligible patients with MIBC treated with KEYTRUDA in combination with enfortumab vedotin-ejfv (n=167) were rash (54%), pruritus (47%), fatigue (47%), peripheral neuropathy (39%), alopecia (35%), dysgeusia (35%), diarrhea (34%), constipation (28%), decreased appetite (28%), nausea (26%), UTI (24%), dry eye (21%), and weight loss (20%).