Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced positive results from two studies from the company’s leading lung cancer research program. Initial results from the Phase 2 KEYNOTE-799 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus concurrent chemoradiation therapy (CCRT) demonstrated an objective response rate (ORR) of 67.0% in Cohort A (squamous and nonsquamous non-small cell lung cancer [NSCLC] patients who received paclitaxel plus carboplatin) and 56.6% in Cohort B (nonsquamous NSCLC patients who received cisplatin plus pemetrexed) in untreated patients with unresectable, locally advanced stage III NSCLC. Additionally, new and updated data from the final analysis of the pivotal Phase 3 KEYNOTE-189 trial showed that 45.7% of patients with metastatic nonsquamous NSCLC treated with KEYTRUDA in combination with chemotherapy were alive at two years versus 27.3% of patients treated with chemotherapy alone.
“KEYTRUDA has become a standard of care in metastatic non-small cell lung cancer based on the strength of clinical data showing a survival benefit as monotherapy or in combination with chemotherapy,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “New data from KEYNOTE-799 demonstrate the potential of KEYTRUDA plus concurrent chemoradiation therapy in earlier stages of lung cancer, while the long-term survival data from KEYNOTE-189 add to the strong body of evidence supporting the use of KEYTRUDA in combination with chemotherapy for appropriate patients with metastatic non-small cell lung cancer.”
“Approximately 20-30% of patients with unresectable stage III non-small cell lung cancer have disease progression after initially receiving chemoradiation,” said Salma K. Jabbour, radiation oncologist, professor, vice chair of clinical research, Rutgers Cancer Institute of New Jersey. “The encouraging results from KEYNOTE-799 demonstrate that combining KEYTRUDA with concurrent chemoradiation therapy has the potential to address a significant unmet medical need.”
Merck is a leader in lung cancer, with an extensive clinical development program evaluating KEYTRUDA, in combination or as monotherapy, for the treatment of lung cancer across all stages of disease and lines of therapy in over 200 trials with more than 10,000 patients. In addition to KEYNOTE-799, Merck has initiated the Phase 3 KEYLYNK-012 study (ClinicalTrials.gov, NCT04380636), which will evaluate KEYTRUDA plus CCRT followed by one year of KEYTRUDA alone or in combination with LYNPARZA® (olaparib) post-CCRT in patients with unresectable, locally advanced stage III NSCLC. KEYLYNK-012 is one of three new pivotal Phase 3 trials evaluating KEYTRUDA in combination with LYNPARZA for NSCLC. Additional studies include KEYLYNK-006 (nonsquamous patients; ClinicalTrials.gov, NCT03976323) and KEYLYNK-008 (squamous patients; ClinicalTrials.gov, NCT03976362), evaluating KEYTRUDA and maintenance LYNPARZA for the first-line treatment of metastatic NSCLC.
Results from KEYNOTE-799 (Abstract #9008) and KEYNOTE-189 (Abstract #9582) are being presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO20.
First Presentation of Data from KEYNOTE-799 in Stage III NSCLC (Abstract #9008)
KEYNOTE-799 (ClinicalTrials.gov, NCT03631784) is a Phase 2, non-randomized, open-label study of 216 untreated patients with unresectable, locally advanced stage IIIA–C NSCLC designed to evaluate the efficacy of KEYTRUDA plus CCRT. All patients received KEYTRUDA, standard thoracic radiotherapy and investigator’s choice of two chemotherapy regimens. Cohort A included patients across NSCLC histologies who received paclitaxel plus carboplatin and Cohort B included only nonsquamous NSCLC patients who received cisplatin plus pemetrexed. Primary endpoints are ORR and rate of Grade ≥3 pneumonitis. Secondary endpoints include progression-free survival (PFS), overall survival (OS) and safety.
In all patients from Cohort A (n=112) and Cohort B (n=53) with a minimum of 15 weeks of follow-up, KEYTRUDA plus CCRT showed an ORR of 67.0% (90% CI, 58.9-74.3) and 56.6% (90% CI, 44.4-68.2) for Cohort A (2.7% complete response [CR]) and Cohort B (3.8% CR), respectively. The median duration of response (DOR) was not reached in either Cohort A (range, 1.6+ to 10.5+) or Cohort B (range, 1.7+ to 10.5+) as of data cutoff. Additionally, 91.1% and 100% of patients in Cohort A and B, respectively, had a response lasting six months or longer. In Cohort A, the six-month PFS rate was 81.4% and the six-month OS rate was 87.2%. In Cohort B, the six-month PFS rate was 85.2% and the six-month OS rate was 94.8%.
The incidence of adverse events (AEs) among patients who received KEYTRUDA plus CCRT was consistent with the established toxicity profiles of CCRT for stage III NSCLC and KEYTRUDA monotherapy. All-cause Grade ≥3 pneumonitis occurred in 8.0% (n=9) of patients in Cohort A and 5.5% (n=4) of patients in Cohort B; four deaths (Grade 5 pneumonitis) occurred in Cohort A. Observed rates of Grade ≥3 pneumonitis were within the expected range for immunotherapy combined with CCRT. The incidence of treatment-related Grades 3-5 AEs was 64.3% (n=72) in Cohort A and 41.1% (n=30) in Cohort B. Treatment-related AEs leading to discontinuation of any treatment component occurred in 28.6% (n=32) of patients in Cohort A and 12.3% (n=9) in Cohort B.
New Two-Year Survival Data from KEYNOTE-189 in Metastatic NSCLC (Abstract #9582)
New and updated data from the protocol-specified final analysis of KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) continue to show that KEYTRUDA in combination with chemotherapy maintained a sustained, long-term survival benefit over chemotherapy alone after 31.0 months of median follow-up. The pivotal Phase 3 KEYNOTE-189 trial evaluated KEYTRUDA in combination with pemetrexed (ALIMTA®) and platinum (cisplatin or carboplatin) chemotherapy for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone in patients with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% (HR=0.56 [95% CI, 0.46-0.69]) compared with chemotherapy alone, with a median OS of 22.0 versus 10.6 months. The two-year OS rate was 45.7% for KEYTRUDA in combination with chemotherapy versus 27.3% with chemotherapy alone. KEYTRUDA in combination with chemotherapy also reduced the risk of disease progression or death by half (HR=0.49 [95% CI, 0.41-0.59]) compared with chemotherapy alone, with a median PFS of 9.0 versus 4.9 months. The two-year PFS rate was 22.0% for KEYTRUDA in combination with chemotherapy versus 3.4% for chemotherapy alone. The ORR was 48.3% for KEYTRUDA in combination with chemotherapy versus 19.9% for chemotherapy alone.
Among the 56 patients who completed two years of treatment with KEYTRUDA, the ORR was 85.7%. Median OS was not reached.
The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with metastatic NSCLC. Grades 3-5 AEs occurred in 72.1% of patients who received KEYTRUDA in combination with chemotherapy and 66.8% of patients who received chemotherapy alone. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of ALIMTA® (pemetrexed).