Therapy Areas: Inflammatory Diseases
US Merck Releases Phase 3 Study Findings of Keytruda Compared to Standard of Care, in Patients with Previously Treated Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
13 September 2017 - - US-based pharmaceutical company Merck (NYSE: MRK) has released results of the phase 3 KEYNOTE-040 trial investigating Keytruda (pembrolizumab), the company's anti-PD-1 therapy, compared to standard treatment (methotrexate, docetaxel or cetuximab) in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy, the company said.

As previously disclosed, the study did not meet its pre-specified primary endpoint of overall survival.

The findings include updated survival data showing a 19% reduction in the risk of death over standard treatment in the intent-to-treat population (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204), with pre-specified p-value required for statistical significance of 0.0175, and a median OS of 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1).

Complete results will be presented for the first time at the European Society for Medical Oncology 2017 Congress in Madrid, Spain, in an oral presentation TODAY from 3:00 3: 12 p.m. CEST (Location: Granada Auditorium) (Abstract #LBA45_PR).

With more than 20 trials, Merck currently has the largest immuno-oncology clinical development program in head and neck cancer and is advancing multiple registration-enabling studies investigating Keytruda (pembrolizumab) as monotherapy and in combination with other cancer treatments including KEYNOTE-048 and KEYNOTE-412.

KEYNOTE-040 is a randomized, multi-center, phase 3 study investigating KEYTRUDA as a monotherapy (n=247) versus standard treatment (methotrexate, docetaxel or cetuximab) (n=248) in patients with recurrent or metastatic HNSCC (additional details on the trial design are provided below).

Data presented at ESMO are based on findings in the intent-to-treat population (n=495) and include analysis of efficacy endpoints based on PD-L1 expression using two measurements: PD-L1 CPS ≥1 (n=387) and PD-L1 TPS ≥50% (n=129).

More than a third of patients in the intent-to-treat population went on to receive subsequent therapy, including 11 of 84 patients in the KEYTRUDA arm and 31 of 100 patients in the standard treatment arm who received subsequent treatment with an immune checkpoint inhibitor.

Other subsequent treatments included chemotherapy, EGFR inhibitor, kinase inhibitor, other immunotherapy, and other treatments.

Data show that in the intent-to-treat population, the median OS was 8.4 months with KEYTRUDA (95% CI, 6.5-9.4) compared to 7.1 months with standard treatment (95% CI, 5.9-8.1) (HR, 0.81 [95% CI, 0.66-0.99]; one sided p = 0.0204); the 12-month OS rate was 37.3 % with KEYTRUDA compared to 27.2 % with standard treatment. Further analysis of the primary endpoint based on PD-L1 expression showed:

In patients with PD-L1 CPS ≥1, the median OS was 8.7 months with KEYTRUDA (95% CI, 6.9-11.4) and 7.1 months with standard treatment (95% CI, 5.7-8.6) (HR, 0.75 [95% CI, 0.59-0.95]; p = 0.0078); the 12-month OS rate was 40.1 % with Keytruda compared to 26.7 % with standard treatment.

In patients with PD-L1 TPS ≥50%, the median OS was 11.6 months with KEYTRUDA (95% CI, 8.3-19.5) and 7.9 months with standard treatment (95% CI, 4.8-9.3) (HR, 0.54 [95% CI, 0.35-0.82]; p = 0.0017); the 12-month OS rate was 46.6% with Keytruda compared to 25.8 % with standard treatment.

The overall response rate in the intent-to-treat population was 14.6 % in the KEYTRUDA (pembrolizumab) arm compared to 10.1 % in the standard treatment arm (p = 0.0610). In patients with PD-L1 CPS ≥1, the ORR was 17.3 % with KEYTRUDA compared to 9.9 % with standard treatment (p = 0.0171). In patients with PD-L1 TPS ≥50%, the ORR was 26.6 % with KEYTRUDA compared to 9.2 % with standard treatment (p = 0.0009).

The median progression-free survival was 2.1 months in the intent-to-treat population with Keytruda (95% CI, 2.1-2.3) and 2.3 months with standard treatment (95% CI, 2.1-2.8) (HR, 0.95 [95% CI, 0.79-1.16]; p = 0.3037).

In patients with PD-L1 CPS ≥1, the median PFS was 2.2 months with KEYTRUDA (95% CI, 2.1-3.0) and 2.3 months with standard treatment (95% CI, 2.1-3.3) (HR, 0.89 [95% CI, 0.72-1.11]; p = 0.1526).

In patients with PD-L1 TPS ≥50%, the median PFS was 3.5 months with KEYTRUDA (95% CI, 2.1-6.3) and 2.2 months with standard treatment (95% CI, 2.0-2.5) (HR, 0.58 [95% CI, 0.39-0.87]; p = 0.0034).

The safety profile of Keytruda was consistent with that observed in previously reported studies. Treatment-related adverse events (TRAEs) of any grade occurred in 155 patients (63.0%) in the Keytruda arm and 196 patients (83.8%) in the standard treatment arm.

Across any arm, TRAEs with incidence of 10% or more included hypothyroidism, fatigue, diarrhea, rash, asthenia, anemia, nausea, mucosal inflammation, stomatitis, decreased neutrophil count and alopecia.

Immune-mediated adverse events, any grade, occurring in the Keytruda arm were hypothyroidism, pneumonitis, infusion reactions, severe skin reactions, hyperthyroidism, colitis, Guillain-Barre syndrome and hepatitis.

Discontinuation due to TRAEs occurred in 15 patients in the KEYTRUDA arm and 12 patients in the standard treatment arm. Deaths due to treatment-related adverse events occurred in four patients in the Keytruda arm and two patients in the standard treatment arm.

KEYNOTE-040 is a randomised, multi-center, pivotal phase 3 study investigating Keytruda as a monotherapy versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic HNSCC.
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