Merck (MRK) Announces Strong KEYTRUDA Data in NSCLC at ESMO 2016; Superior OS Noted

October 10, 2016 6:27 AM EDT

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Merck (NYSE: MRK) announced that KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, demonstrated superiority in overall survival (OS) at 18 months compared to standard of care chemotherapy (docetaxel) in patients with metastatic non-small cell lung cancer (NSCLC) previously treated with platinum-containing chemotherapy whose tumors expressed PD-L1 (tumor proportion score [TPS] of one percent or more), as well as patients with high levels of PD-L1 expression (TPS of 50 percent or more). These data, from the phase 2/3 KEYNOTE-010 trial, will be presented at the ESMO 2016 Congress, the annual meeting of the European Society for Medical Oncology, in Copenhagen (Abstract #LBA48).

“These findings – which show superior survival with longer follow-up across patients with PD-L1 expression (tumor proportion score of one percent or more), as well as improved quality of life – point to KEYTRUDA as a durable treatment option for many previously treated patients with advanced non-small cell lung cancer,” said Roy S. Herbst, M.D., Ph.D., professor of medicine and chief of medical oncology, Yale Cancer Center and Smilow Cancer Hospital at Yale New Haven. “These data also reinforce the value of using PD-L1 as a biomarker to identify patients who are likely to benefit from KEYTRUDA.”

In additional data at the ESMO 2016 Congress from KEYNOTE-010, an analysis of patient-reported health-related quality of life outcomes showed more patients treated with KEYTRUDA (pembrolizumab) reported positive outcomes compared to patients treated with chemotherapy (Abstract #1219P).

Separately at the ESMO 2016 Congress, researchers presented an analysis of PD-L1 prevalence across three separate studies, including KEYNOTE-010. Overall, 66 percent of patients with metastatic NSCLC expressed any level of PD-L1, and 28 percent expressed high levels of PD-L1 (Abstract #1060P).

“Our research in immuno-oncology continues to show tremendous promise, with our goal being to extend the lives of significant numbers of patients with non-small cell lung cancer,” said Roger Dansey, M.D., senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “In this longer-term analysis of KEYNOTE-010, among patients who responded to treatment, four times as many patients receiving KEYTRUDA were still alive without disease progression compared to docetaxel. It is gratifying to see these results continue with additional follow-up.”

Merck has a robust clinical development program for KEYTRUDA in lung cancer, with multiple registration-enabling studies currently underway. The KEYTRUDA clinical development program includes more than 30 tumor types in more than 350 clinical trials, including more than 100 trials that combine KEYTRUDA with other cancer treatments.

Efficacy and Safety Findings from KEYNOTE-010 (Abstract #LBA48)

KEYNOTE-010 is a global, open-label, randomized, pivotal phase 2/3 study evaluating KEYTRUDA (2 mg/kg or 10 mg/kg every three weeks) compared to standard of care chemotherapy (docetaxel, 75 mg/m2 every three weeks) in patients with previously treated metastatic NSCLC. The primary endpoints were OS and progression-free survival (PFS) and were assessed based on patients whose tumors expressed PD-L1 (TPS of one percent or more) and high levels of PD-L1 (TPS of 50 percent or more). Secondary endpoints included overall response rate (ORR) and duration of response. KEYNOTE-010 is the first study of its kind to evaluate the potential of an immunotherapy compared to chemotherapy based on prospective measurement of PD-L1 expression in patients with metastatic NSCLC. As previously announced, the study met its primary objective, showing that KEYTRUDA significantly improved OS compared to chemotherapy in patients with PD-L1 expression (TPS of one percent or more). Findings were similar in patients who received the FDA-approved dose of KEYTRUDA (2 mg/kg every three weeks) and an investigational dose of KEYTRUDA (10 mg/kg every three weeks). These data also served as the basis for the KEYTRUDA (pembrolizumab) application approval by the European Medicines Agency (EMA) in July of this year and are currently under review by the U.S. Food and Drug Administration (FDA) for the second-line or greater NSCLC treatment setting.

At the ESMO 2016 Congress, data from this study of 1,034 patients included six months of additional follow-up, with a median follow-up of 19.2 months (range, 11.7-29.7), and showed superior outcomes of OS, PFS, and ORR with KEYTRUDA compared to docetaxel in patients with PD-L1 expression (TPS of one percent or more) as well as high levels of PD-L1 expression (TPS of 50 percent or more) – with consistency of outcomes across KEYTRUDA doses.

In patients with PD-L1 expression (TPS of one percent or more), OS at 18 months was 37 percent (HR, 0.72 [95% CI, 0.60-0.87]; p=0.0003) with KEYTRUDA 2 mg/kg, 43 percent (HR, 0.60 [95% CI, 0.50-0.73]; p<0.00001) with KEYTRUDA 10 mg/kg, and 24 percent with docetaxel. Among all patients, median OS was 10.5 months with KEYTRUDA 2 mg/kg, 13.6 months with KEYTRUDA 10 mg/kg, and 8.6 months with docetaxel. ORR was 19 percent (95% CI, 15-23, p=0.00025) with KEYTRUDA 2 mg/kg, 20 percent (95% CI, 16-25, p=0.00004) with KEYTRUDA 10 mg/kg and 10 percent (95% CI, 7-13) with docetaxel. Responses to KEYTRUDA continued to be durable; among patients with any level of PD-L1 expression who responded to treatment, 60 percent on each of the KEYTRUDA treatment arms were alive, progression-free, and had not received additional therapy for their disease, compared to 15 percent in the docetaxel treatment arm.

In patients with high levels of PD-L1 expression (TPS of 50 percent or more), OS at 18 months was 46 percent (HR, 0.54 [95% CI, 0.39-0.73]; p=0.00004) with KEYTRUDA 2 mg/kg, 52 percent with KEYTRUDA 10 mg/kg (HR, 0.48 [95% CI, 0.35-0.66]; p<0.00001), and 24 percent with docetaxel. In this group, median OS was 15.8 months with KEYTRUDA 2 mg/kg, 18.8 months with KEYTRUDA 10 mg/kg, and 8.2 months with docetaxel. ORR was 29 percent (95% CI, 22-38, p<0.00001) with KEYTRUDA 2 mg/kg, 32 percent (95% CI, 24-40, p<0.00001) with KEYTRUDA 10 mg/kg, and nine percent (95% CI, 5-14) with docetaxel. Responses to KEYTRUDA continued to be durable; among patients with high levels of PD-L1 expression who responded to treatment, 68 and 63 percent on the KEYTRUDA 2 mg/kg and 10 mg/kg treatment arms, respectively, were alive, progression-free, and had not received additional therapy for their disease, compared to 15 percent in the docetaxel treatment arm.

The safety profile of KEYTRUDA was consistent with that observed in previously reported studies of KEYTRUDA. Treatment-related adverse events remained lower with KEYTRUDA compared to docetaxel. Among the total study population, 13, 17, and 36 percent of patients experienced Grades 3-5 treatment-related adverse events with KEYTRUDA (pembrolizumab) 2 mg/kg, KEYTRUDA 10 mg/kg, and docetaxel, respectively. Compared with the previous analysis, two additional patients in the KEYTRUDA 2 mg/kg arm and five patients in the KEYTRUDA 10 mg/kg arm experienced immune-mediated adverse events, none of which led to death. Grade 3-5 immune-mediated adverse events that occurred in two or more patients included pneumonitis (n=14), severe skin toxicities (n=8), and colitis (n=4). Additional immune-mediated adverse events observed in at least two patients in the KEYTRUDA arms of the study included hypothyroidism, hyperthyroidism, pancreatitis, adrenal insufficiency, myositis, thyroiditis, hepatitis, hypophysitis, and type 1 diabetes mellitus. In this study to date, there have been 10 treatment-related adverse events that led to death, two with KEYTRUDA 2 mg/kg, three with KEYTRUDA 10 mg/kg, and five with docetaxel.

These data will be presented in a poster discussion session on Oct. 9 from 2:45 – 4:15 p.m. CEST (Abstract #LBA48) (Location: Oslo).

Patient-Reported Outcomes Findings from KEYNOTE-010 (Abstract #1219P)

Also reported at the ESMO 2016 Congress were health-related quality of life (HRQoL) outcomes from the KEYNOTE-010 trial. Findings were based on patient-reported assessments using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Lung Cancer 13, and EuroQol-5D-3L instruments to measure for outcomes such as physical, role, emotional, cognitive, and social functioning, as well as lung cancer and treatment-related symptoms, among other measures.

Overall, from baseline to the 12-week assessment, patients treated with KEYTRUDA (2 mg/kg or 10 mg/kg every three weeks) reported numeric improvements, some of which were significant, in HRQoL and prolonged time to deterioration of lung cancer symptoms (defined using a composite endpoint of cough, dyspnea, and chest pain) compared with docetaxel (75 mg/m2 every three weeks).

These findings, along with results from additional patient-reported outcomes analyses, suggest that HRQoL and symptoms were maintained or improved more with KEYTRUDA than with docetaxel.

These data were presented in a poster session on Oct. 8 from 1 – 2 p.m. CEST (Location: Hall E).

PD-L1 Prevalence Findings from KEYNOTE-001, -010, and -024 (Abstract #1060P)

Results from a third NSCLC abstract at the ESMO 2016 Congress explored, for the first time, the prevalence of PD-L1 in patients screened across multiple studies. The analysis assessed 4,784 patients with NSCLC who had tumors evaluable for PD-L1 expression and were screened for eligibility in three registrational studies of KEYTRUDA (pembrolizumab) – KEYNOTE-001, KEYNOTE-010, and KEYNOTE-024. Based on this pooled analysis, 66 percent of patients across all three trials were determined to express PD-L1 (TPS of one percent or more) and 28 percent were determined to have high levels of PD-L1 expression (TPS of 50 percent or more). These findings were similar across demographic and disease characteristics examined, including prior lines of therapy, age, tumor source (primary and metastases), and histology (squamous and non-squamous).

These data will be presented in a poster session on Oct. 9 from 1 – 2 p.m. CEST (Location: Hall E).



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