Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin — ejfv) as Perioperative Treatment for Adults With Resectable Muscle — Invasive Bladder Cancer (MIBC)

For best results when printing this announcement, please click on link below: Merck Receives Positive EU CHMP Opinion for KEYTRUDA(®) (pembrolizumab) Plus Padcev(®) (enfortumab vedotin-ejfv) as Perioperative Treatment for Adults With Resectable Muscle-Invasive Bladder Cancer (MIBC) Opinion granted based on positive results from the Phase 3 KEYNOTE-B15 trial, which demonstrated improvements in event-free survival, overall survival and pathologic complete response rate If approved, KEYTRUDA plus Padcev would become the first and only PD-1 inhibitor plus antibody-drug conjugate regimen for patients with MIBC regardless of cisplatin eligibility in the European Union Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of 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).

], will now be reviewed by the European Commission (EC) for marketing authorization in the European Union (EU), Iceland, Liechtenstein and Norway. A final decision is expected by the fourth quarter of 2026. “Despite advances in the treatment of muscle-invasive bladder cancer, recurrence remains a significant concern for many patients regardless of cisplatin eligibility, and up to half may be unable to receive cisplatin-based chemotherapy,” said Dr. Marjorie Green, senior vice president, oncology, global clinical development, Merck Research Laboratories.

” The recommendation 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. 2%). 2%) did not receive surgery due to adverse reactions. 2% each).

Of the 351 patients who received neoadjuvant treatment with KEYTRUDA in combination with enfortumab vedotin-ejfv and underwent radical cystectomy, 26 patients (7%) experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions. 6% each). 4% each). 2% each).

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%). 4%). 6% each). 4% each).

2% each). 2%) did not receive surgery due to adverse reactions. 6% each). 1%) experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

1% each). Fatal adverse reactions occurred in 7% of patients, including urosepsis, intracranial hemorrhage, death, myocardial infarction, multiple organ dysfunction syndrome, and pseudomonal pneumonia (1% each). Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 29% of patients; the most frequent (>2%) were diarrhea (5%), peripheral neuropathy, acute kidney injury, and pneumonitis (2% each). In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC.

4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%). Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent. In KEYNOTE-811, fatal adverse reactions occurred in 3 patients who received KEYTRUDA in combination with trastuzumab and CAPOX (capecitabine plus oxaliplatin) or FP (5-FU plus cisplatin) and included pneumonitis in 2 patients and hepatitis in 1 patient. KEYTRUDA was discontinued due to adverse reactions in 13% of 350 patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. 1%).

In the KEYTRUDA arm vs placebo, there was a difference of ≥5% incidence between patients treated with KEYTRUDA vs standard of care for diarrhea (53% vs 47%), rash (35% vs 28%), hypothyroidism (11% vs 5%), and pneumonia (11% vs 5%). In KEYNOTE-859, when KEYTRUDA was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in 45% of 785 patients. 4%). 3%).

KEYTRUDA was permanently discontinued due to adverse reactions in 15% of patients. 0%). The most common adverse reactions (reported in ≥20%) in patients receiving KEYTRUDA in combination with chemotherapy were peripheral neuropathy (47%), nausea (46%), fatigue (40%), diarrhea (36%), vomiting (34%), decreased appetite (29%), abdominal pain (26%), palmar-plantar erythrodysesthesia syndrome (25%), constipation (22%), and weight loss (20%).

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in 15% of 370 patients. 1%). The most common adverse reactions (≥20%) with KEYTRUDA in combination with chemotherapy were nausea (67%), fatigue (57%), decreased appetite (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight loss (24%).

Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. 3%) of large intestinal perforation, urosepsis, sepsis, and vaginal hemorrhage. 4%), and sepsis (1%). KEYTRUDA was discontinued for adverse reactions in 9% of patients.

The most common adverse reaction (≥1%) resulting in permanent discontinuation was diarrhea (1%). For patients treated with KEYTRUDA in combination with CRT, the most common adverse reactions (≥10%) were nausea (56%), diarrhea (51%), urinary tract infection (35%), vomiting (34%), fatigue (28%), hypothyroidism (23%), constipation (20%), weight loss (19%), decreased appetite (18%), pyrexia (14%), abdominal pain and hyperthyroidism (13% each), dysuria and rash (12% each), back and pelvic pain (11% each), and COVID-19 (10%).

6% of patients, including 3 cases of hemorrhage, 2 cases each of sepsis and due to unknown causes, and 1 case each of acute myocardial infarction, autoimmune encephalitis, cardiac arrest, cerebrovascular accident, femur fracture with perioperative pulmonary embolus, intestinal perforation, and pelvic infection. 3% each). KEYTRUDA was discontinued in 15% of patients due to adverse reactions. The most common adverse reaction resulting in permanent discontinuation (≥1%) was colitis (1%).

For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥20%) were peripheral neuropathy (62%), alopecia (58%), anemia (55%), fatigue/asthenia (53%), nausea and neutropenia (41% each), diarrhea (39%), hypertension and thrombocytopenia (35% each), constipation and arthralgia (31% each), vomiting (30%), urinary tract infection (27%), rash (26%), leukopenia (24%), hypothyroidism (22%), and decreased appetite (21%).

For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥20%) were peripheral neuropathy (58%), alopecia (56%), fatigue (47%), nausea (40%), diarrhea (36%), constipation (28%), arthralgia (27%), vomiting (26%), hypertension and urinary tract infection (24% each), and rash (22%). In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with previously treated recurrent or metastatic cervical cancer. 1% each).

The most common adverse reactions (≥20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%). In KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in 13% of 299 patients with previously treated hepatocellular carcinoma. 3%). The most common adverse reactions in patients receiving KEYTRUDA (≥10%) were pyrexia (18%), rash (18%), diarrhea (16%), decreased appetite (15%), pruritus (12%), upper respiratory tract infection (11%), cough (11%), and hypothyroidism (10%).

In KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in 15% of 529 patients with locally advanced unresectable or metastatic biliary tract cancer. 3%). Adverse reactions leading to the interruption of KEYTRUDA occurred in 55% of patients. 3%).

In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent. 3% of 429 patients. 3%), dehydration (1%), and pneumonitis (1%). 2%).

The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%). In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in 20% of patients receiving KEYTRUDA; the serious adverse reactions (≥1%) were acute kidney injury, adrenal insufficiency, pneumonia, colitis, and diabetic ketoacidosis (1% each).

2% including 1 case of pneumonia. 6%), colitis (1%), and adrenal insufficiency (1%). The most common adverse reactions (≥20%) were musculoskeletal pain (41%), fatigue (40%), rash (30%), diarrhea (27%), pruritus (23%), and hypothyroidism (21%). In KEYNOTE-868, when KEYTRUDA was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in 35% of patients receiving KEYTRUDA in combination with chemotherapy, compared to 19% of patients receiving placebo in combination with chemotherapy (n=377).

3%). KEYTRUDA was discontinued for an adverse reaction in 14% of patients.