Merck ( MSD ) has withdrawn its European application for Keytruda ( Pembrolizumab ) in combination with Pemetrexed and Carboplatin as a first-line treatment for metastatic nonsquamous non-small cell lung cancer ( NSCLC ).

The application was based on findings from KEYNOTE-021, Cohort G.

Clinical data have demonstrated significant improvements in overall response rate ( ORR ) and progression-free survival ( PFS ) for Keytruda combination regimen compared to chemotherapy alone.
Additionally, the broad clinical development Program includes a number of studies evaluating Keytruda in combination with chemotherapy in the first-line NSCLC setting.
Merck looks forward to sharing data from these studies with regulatory authorities and the medical community as they become available.

Pembrolizumab 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.
Pembrolizumab 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.

Keytruda indications

Melanoma: Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung cancer: Keytruda, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer ( NSCLC ) whose tumors have high PD-L1 expression [ tumor proportion score ( TPS ) greater than or equal to 50% ] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
Keytruda, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 ( TPS greater than or equal to 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.
Keytruda, in combination with Pemetrexed and Carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved from FDA ( Food and Drug Administration ) under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering Keytruda in combination with chemotherapy, Keytruda should be administered prior to chemotherapy when given on the same day.

Head and neck cancer: Keytruda is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma ( HNSCC ) with disease progression on or after Platinum-containing chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin lymphoma: Keytruda is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma ( cHL ), or who have relapsed after three or more prior lines of therapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In adults with cHL, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
In pediatric patients with cHL, Keytruda is administered at a dose of 2 mg/kg ( up to a maximum of 200 mg ) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial carcinoma: Keytruda is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy.
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 the confirmatory trials.
Keytruda is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with Platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High ( MSI-H ) 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.
This indication is approved under accelerated approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The safety and effectiveness of Keytruda in pediatric patients with MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, Keytruda is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
In children with MSI-H cancer, Keytruda is administered at a dose of 2 mg/kg ( up to a maximum of 200 mg ) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Gastric cancer: Keytruda is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction ( GEJ ) adenocarcinoma whose tumors express PD-L1 [ Combined Positive Score ( CPS ) greater than or equal to 1 ] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and Platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
The recommended dose of Keytruda is 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. ( Xagena )

Source: Merck ( MSD ), 2017

XagenaMedicine2017