Benzinga | Sep 20, 2020 08:34AM EDT

Merck, Eisai Present First-Time Data From Two Studies Evaluating KEYTRUDA Plus LENVIMA in Seven Different Tumor Types at ESMO 2020

Merck (NYSE:MRK) and Eisai (OTC:ESALY)today announced new investigational data from two trials under the LEAP (LEnvatinib And Pembrolizumab) clinical program evaluating KEYTRUDA, Merck's anti-PD-1 therapy, plus LENVIMA, the orally available multiple receptor tyrosine kinase inhibitor discovered by Eisai. In the Phase 2 LEAP-004 trial, KEYTRUDA plus LENVIMA showed an objective response rate (ORR) of 21.4% (95% CI: 13.9-30.5) in patients with unresectable or advanced melanoma who had previously progressed on an anti-PD-1/PD-L1 therapy. In the Phase 2 LEAP-005 trial, KEYTRUDA plus LENVIMA demonstrated an ORR that ranged from 9.7-32.3% (95% CI: 2.0-51.4) in previously treated patients with triple-negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (non-microsatellite instability-high [non-MSI-H]/mismatch repair proficient [pMMR]), glioblastoma multiforme (GBM) and biliary tract cancer (BTC). Results from LEAP-004 (Abstract #LBA44) and LEAP-005 (Abstract #LBA41) were accepted as late-breaking abstracts and are being presented in proffered paper presentations at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

"These new data from our LEAP clinical program show encouraging activity across several aggressive cancer types and expand our knowledge about the potential of KEYTRUDA plus LENVIMA to help a range of patients with these cancers," said Dr. Scot Ebbinghaus, Vice President, Clinical Research, Merck Research Laboratories. "This is the first time that clinical data from two LEAP trials are being presented, reflecting important progress we are making to explore the potential of this combination for patients in need of new options, particularly those with advanced melanoma who have progressed on an anti-PD-1 or PD-L1 therapy."

"We are encouraged by the growing body of research that we have seen to date, now in 13 different cancers, supporting the potential of the KEYTRUDA plus LENVIMA combination, which we're currently evaluating in 19 clinical trials," said Dr. Takashi Owa, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. "These data not only help advance our understanding of the regimen but also fuel our deep-seated determination to work to address the unmet needs of these patients."

LEAP-004 Trial Design and Data (Abstract #LBA44)

LEAP-004 (ClinicalTrials.gov, NCT03776136) is a Phase 2, single-arm, open-label trial evaluating KEYTRUDA in combination with LENVIMA in patients with unresectable or advanced melanoma who had progressed on an anti-PD-1/PD-L1 therapy within 12 weeks. Patients were treated with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression in combination with KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or disease progression for up to 35 cycles (approximately two years). The primary endpoint is ORR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by blinded independent central review (BICR). Secondary endpoints include progression-free survival (PFS) and duration of response (DOR) per RECIST v1.1 by BICR, overall survival (OS) and safety.

At data cutoff (June 10, 2020), a total of 103 patients were enrolled and treated. With a median duration of follow-up of 12 months (range: 8.7-15.6), KEYTRUDA plus LENVIMA demonstrated an overall ORR by BICR of 21.4% (n=22) (95% CI: 13.9-30.5), with a complete response rate of 1.9% (n=2) and a partial response rate of 19.4% (n=20). In the total study population, the median DOR was 6.3 months (range: 2.1+ to 11.1+), with 72.6% (95% CI: 46.2-87.6) of responses lasting for at least six months. Median PFS was 4.2 months (range: 3.5 to 6.3), with 73.8% of patients experiencing disease progression or death, and the nine-month PFS rate was 26.2% (95% CI: 17.4-35.9). Median OS was 13.9 months (range: 10.8-not reached [NR]), with death occurring in 44.7% of patients, and the nine-month OS rate was 65.4% (95% CI: 55.2-73.8).

The exploratory analysis showed that specifically in the 29 patients whose disease progressed after an anti-PD-1/L1 therapy plus an anti-CTLA-4 therapy, the ORR by BICR was 31.0% (95% CI: 15.3-50.8), with a complete response rate of 3.4% (n=1) and a partial response rate of 27.6% (n=8), and the disease control rate (DCR) by BICR was 62.1% (95% CI: 42.3-79.3). In the total study population, the DCR by BICR was 65.0% (95% CI: 55.0-74.2).

Treatment-related adverse events (TRAEs) led to discontinuation of KEYTRUDA and/or LENVIMA in 7.8% of patients. Grade 3-5 TRAEs occurred in 44.7% of patients (Grade 3: 39.8%; Grade 4: 3.9%; Grade 5: 1.0%), and serious TRAEs occurred in 18.4% of patients. The most common TRAEs of any grade occurring in at least 30% of the overall study population were hypertension (56.3%), diarrhea (35.9%), nausea (34.0%), hypothyroidism (33.0%) and decreased appetite (31.1%).

LEAP-005 Trial Design and Data (Abstract #LBA41)

LEAP-005 (ClinicalTrials.gov, NCT03797326) is a Phase 2, single-arm, open-label trial evaluating KEYTRUDA in combination with LENVIMA in patients with select previously treated advanced solid tumors. The study cohorts are TNBC, ovarian cancer, gastric cancer, colorectal cancer (non-MSI-H/pMMR), GBM and BTC. Patients were treated with LENVIMA 20 mg orally once daily until unacceptable toxicity or disease progression in combination with KEYTRUDA 200 mg intravenously every three weeks until unacceptable toxicity or disease progression for up to 35 cycles (approximately two years). The primary endpoints are ORR per RECIST v1.1 as assessed by BICR or Response Assessment in Neuro-Oncology (RANO) criteria (for GBM only) as assessed by BICR, and safety. Secondary endpoints include DCR per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, DOR per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, PFS per RECIST v1.1 by BICR or RANO (for GBM only) by BICR, and OS.

At data cutoff (April 10, 2020), a total of 187 patients were enrolled and treated. The confirmed ORR after a median duration of follow-up of 8.6 months (range: 1.9-13.1) for the six different tumor types, as well as additional efficacy and safety results, showed:

2L/3L TNBC(n=31)4L Ovarian(n=31)3L Gastric(n=31)3L Colorectal(n=32)2L BTC(n=31)2L GBM(n=31)ORR, % (95% CI)29.0 (14.2-48.0)32.3 (16.7-51.4)9.7 (2.0-25.8)21.9 (9.3-40.0)9.7 (2.0-25.8)16.1 (5.5-33.7)DCR, % (95% CI)58.1 (39.1-75.5)74.2 (55.4-88.1)48.4 (30.2-66.9)46.9 (29.1-65.3)67.7 (48.6-83.3)58.1 (39.1-75.5)DOR, median (range), monthsNR (0.0+ to 8.4+)NR (1.5+ to 7.9+)NR (2.1+ to 2.3+)NR (2.1+ to 10.4+)5.3 (2.1+ to 6.2)3.2 (2.5 to 4.9+)Grade 3 TRAEs, % (n)55 (17)68 (21)42 (13)50 (16)48 (15)35 (11)Death due to a TRAE, % (n)3 (1)3 (1)3 (1)3 (1)0 (0)3 (1)Discontinued due to a TRAE, % (n)10 (3)13 (4)6 (2)9 (3)6 (2)6 (2)+, no progressive disease (PD) as of last disease assessment; DCR, disease control rate (best confirmed response: complete/partial response; stable disease); DOR, duration of response; NR, not reachedThe most common TRAEs of any grade occurring in at least 20% of the overall study population were hypertension (39.0%), fatigue (29.4%), diarrhea (26.7%), decreased appetite (25.1%), hypothyroidism (27.8%) and nausea (21.9%). The study is ongoing and will be expanded to enroll approximately 100 patients in each cohort.

About KEYTRUDA(r) (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 1,200 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.