Benzinga | Oct 22, 2021 06:46AM EDT

Merck Reports European Commission Approves Co.'s KEYTRUDA Plus Chemo As Treatment For Certain Patients With Locally Recurrent Unresectable Or Metastatic Triple-Negative Breast Cancer

KEYTRUDA Is Now Approved in Combination With Chemotherapy as First-Line Treatment for Patients With Locally Recurrent Unresectable or Metastatic TNBC Whose Tumors Express PD-L1 (CPS ?10) and Who Have Not Received Prior Chemotherapy for Metastatic Disease

KEYTRUDA Is the First Anti-PD-1 Therapy in Combination With Chemotherapy to Demonstrate Statistically Significant Overall Survival in These Patients; Based on Results From the Phase 3 KEYNOTE-355 Study

KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the European Commission (EC) has approved KEYTRUDA, Merck's anti-PD-1 therapy, in combination with chemotherapy for the first-line treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ?10) and who have not received prior chemotherapy for metastatic disease. Triple-negative breast cancer is an aggressive type of breast cancer. This represents KEYTRUDA's first approval in Europe in a breast cancer setting.

The approval is based on final analysis from the Phase 3 KEYNOTE-355 trial, in which KEYTRUDA in combination with chemotherapy (nab-paclitaxel, paclitaxel or gemcitabine/carboplatin) significantly improved overall survival (OS), reducing the risk of death by 27% (HR=0.73 [95% CI, 0.55-0.95]; p=0.0093), and progression-free survival (PFS), reducing the risk of disease progression or death by 34% (HR=0.66 [95% CI, 0.50-0.88]; p=0.0018) compared to chemotherapy alone in these patients. In this trial, 38% of enrolled patients had tumors expressing PD-L1 with CPS ?10.

"This approval is an important milestone for appropriate patients with metastatic TNBC who are in need of new treatment options," said Dr. Javier Cort?s, head of the International Breast Cancer Center (IBCC), Quironsalud Group. "With this approval, patients in Europe with metastatic TNBC whose tumors express PD-L1 (CPS ?10) have a new immunotherapy treatment option that can be used in combination with different chemotherapy agents."

"At Merck, we are committed to improving outcomes for people with difficult-to-treat cancers, such as TNBC, around the world and are proud of this first European approval for KEYTRUDA in a breast cancer setting," said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. "Now patients with metastatic TNBC who have tumors that express PD-L1 (CPS ?10) in Europe have the new option of KEYTRUDA in combination with chemotherapy, a regimen that has shown significant improvement in overall survival. Today marks an important step forward in the treatment of this aggressive disease."

This approval allows marketing of the combination with KEYTRUDA in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland.

Merck is committed to delivering meaningful advances in breast cancer and women's cancers. The company is rapidly advancing a broad portfolio in gynecologic and breast cancers through an extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across these areas.

Data Supporting the European Approval

The approval was based on data from KEYNOTE-355 (NCT02819518), a multicenter, randomized, placebo-controlled, Phase 3 trial that enrolled 847 patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the advanced setting. Patients were randomized 2:1 to receive KEYTRUDA (200 mg every three weeks) plus chemotherapy (investigator's choice of paclitaxel, nab-paclitaxel or gemcitabine/carboplatin) or placebo plus chemotherapy. Treatment with KEYTRUDA or placebo, both in combination with chemotherapy, continued until disease progression, unacceptable toxicity or a maximum of 24 months. Patients could continue to be treated with chemotherapy, per standard of care. Patients could continue to be treated with KEYTRUDA beyond RECIST-defined disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. The dual primary efficacy outcome measures were OS and PFS. Secondary efficacy outcome measures included objective response rate and duration of response.

In the final analysis of the study, median OS was 23.0 months (95% CI, 19.0-26.3) with KEYTRUDA plus chemotherapy versus 16.1 months (95% CI, 12.6-18.8) with chemotherapy alone. Median PFS was 9.7 months (95% CI, 7.6-11.3) with KEYTRUDA plus chemotherapy versus 5.6 months (95% CI, 5.3-7.5) with chemotherapy alone.

The safety of KEYTRUDA in combination with chemotherapy has been evaluated in 2,033 patients with non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal carcinoma or TNBC receiving 200 mg, 2 mg/kg bodyweight (bw) or 10 mg/kg bw KEYTRUDA every three weeks in clinical studies. In this patient population, the most frequent adverse reactions were anemia (52%), nausea (52%), fatigue (37%), constipation (34%), neutropenia (33%), diarrhea (32%), decreased appetite (30%) and vomiting (28%). Incidences of Grades 3-5 adverse reactions were 67% for KEYTRUDA plus chemotherapy and 66% for chemotherapy alone in patients with NSCLC; 85% for KEYTRUDA plus chemotherapy and 84% for chemotherapy plus cetuximab in patients with HNSCC; 86% for KEYTRUDA plus chemotherapy and 83% for chemotherapy alone in patients with esophageal carcinoma; and 78% for KEYTRUDA plus chemotherapy and 74% for chemotherapy alone in patients with TNBC.