European Commission Approves Expanded Indication for Merck?s KEYTRUDA? (pembrolizumab) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma (cHL)
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 an expanded label for KEYTRUDA, Merck?s anti-PD-1 therapy, as monotherapy for the treatment of adult and pediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. This approval is based on results from the pivotal Phase 3 KEYNOTE-204 trial, in which KEYTRUDA monotherapy demonstrated a significant improvement in progression-free survival (PFS) compared with brentuximab vedotin (BV), a commonly used treatment. KEYTRUDA reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88]; p=0.0027) and showed a median PFS of 13.2 months versus 8.3 months for patients treated with BV. The approval is also based on supportive data from an updated analysis of the KEYNOTE-087 trial; KEYNOTE-087 was the basis for the 2017 EC approval of KEYTRUDA for the treatment of adult patients with relapsed or refractory cHL who have failed ASCT and BV or who are transplant ineligible and have failed BV. This approval is the first pediatric approval for KEYTRUDA in the European Union (EU).
?The European Commission?s approval of an expanded use of KEYTRUDA provides another option for adult and pediatric patients with classical Hodgkin lymphoma who have disease progression after earlier lines of therapy or relapse after transplantation,? said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. ?We are driven to advance therapies to help improve outcomes for patients with blood cancers, including those with relapsed or refractory classical Hodgkin lymphoma, through our broad clinical program.?
This approval allows marketing of KEYTRUDA monotherapy in all 27 EU member states plus Iceland, Lichtenstein, Norway and Northern Ireland.
Merck is continuing to study KEYTRUDA across hematologic malignancies through a broad clinical program, including multiple registrational trials in cHL and primary mediastinal large B-cell lymphoma and more than 60 investigator-initiated studies across 15 tumors. In addition to KEYTRUDA, Merck is evaluating several clinical-stage assets for the treatment of patients with hematologic malignancies, including MK-1026 (formerly known as ARQ 531), a Bruton?s tyrosine kinase inhibitor, and MK-2140 (formerly known as VLS-101), an antibody-drug conjugate targeting ROR1.
Data Supporting the European Approval
The approval was based on data from KEYNOTE-204 (NCT02684292), a randomized, open-label, active-controlled study conducted in 304 patients with relapsed or refractory cHL. Patients were randomized 1:1 to receive either KEYTRUDA 200 mg intravenously every three weeks or BV 1.8 mg/kg intravenously every three weeks. Randomization was stratified by prior ASCT (yes vs. no) and disease status after frontline therapy (primary refractory vs. relapse less than 12 months after completion vs. relapse 12 months or more after completion). Treatment with KEYTRUDA was continued until unacceptable toxicity, documented disease progression or a maximum of 35 cycles. Disease assessment was performed every 12 weeks. The primary efficacy measure was PFS and the secondary efficacy outcome measure was objective response rate (ORR), both assessed by blinded independent central review (BICR) according to the 2007 revised International Working Group (IWG) criteria. KEYNOTE-204 is ongoing to assess the additional primary efficacy outcome measure of overall survival (OS).
In KEYNOTE-204, KEYTRUDA reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.48-0.88]; p=0.0027) and showed a median PFS of 13.2 months (95% CI, 10.9-19.4) compared with 8.3 months (95% CI, 5.7-8.8) for patients treated with BV. For patients treated with KEYTRUDA, the ORR was 66% (95% CI, 57-73), with a complete response (CR) rate of 25% and a partial response (PR) rate of 41%. For patients treated with BV, the ORR was 54% (95% CI, 46-62), with a CR rate of 24% and a PR rate of 30%. The difference in ORRs was not statistically significant. Among the responding patients, median duration of response (DOR) was 20.7 months (range, 0.0+ to 33.2+) with KEYTRUDA versus 13.8 months (range, 0.0+ to 33.9+) with BV.
In this trial, the median duration of exposure to KEYTRUDA was 10 months (range, 1 day to 2.2 years), with 68% of patients receiving at least six months of treatment and 48% receiving at least one year of treatment. Serious adverse reactions occurred in 30% of patients who received KEYTRUDA. Serious adverse reactions in =1% of patients included pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney injury, febrile neutropenia and sepsis. Three patients (2%) died from causes other than disease progression: two from complications after allogeneic HSCT and one from an unknown cause. Permanent discontinuation of KEYTRUDA due to an adverse reaction occurred in 14% of patients; discontinuation of treatment due to pneumonitis occurred in 7% of patients. Dosage interruption of KEYTRUDA due to an adverse reaction occurred in 30% of patients. Adverse reactions that required dosage interruption in =3% of patients were upper respiratory tract infection, pneumonitis, transaminase increase and pneumonia. Thirty-eight percent of patients had an adverse reaction requiring systemic corticosteroid therapy. The most common adverse reactions (=20%) were upper respiratory tract infection (41%), musculoskeletal pain (32%), diarrhea (22%), and pyrexia, fatigue, rash and cough (20% each).
About Hodgkin Lymphoma in Europe
Hodgkin lymphoma is a type of lymphoma that develops in the white blood cells called lymphocytes, which are part of the immune system. Hodgkin lymphoma can start almost anywhere ? most often in lymph nodes in the upper part of the body, with the most common sites being in the chest, neck or under the arms. In the EU, there were nearly 20,000 new cases of Hodgkin lymphoma diagnosed, and nearly 4,000 people died from the disease in 2020. Classical Hodgkin lymphoma accounts for approximately nine in 10 cases of Hodgkin lymphoma.
About KEYTRUDA??(pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body?s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry?s largest immuno-oncology clinical research program. There are currently more than 1,300 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA??(pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) =1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS =1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) =1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS =10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
- solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.