– Interim results of first evaluable cohort (metastatic endometrial cancer) of Study 111, the Phase 1b/2 trial evaluating lenvatinib in combination with pembrolizumab in selected solid tumors, to be presented at 2017 ASCO Annual Meeting
WOODCLIFF LAKE, NJ, USA I June 3, 2017 I Eisai Inc. today announced interim results from the first evaluable cohort of Study 111, a Phase 1b/2 study investigating lenvatinib (marketed as Lenvima®), a multiple receptor tyrosine kinase inhibitor, in combination with Merck’s (known as MSD outside the United States and Canada) pembrolizumab (marketed as KEYTRUDA®), an anti-PD-1 therapy, in patients with selected solid tumors. In this cohort of previously treated patients (median = 2 prior therapies) with metastatic endometrial cancer (n=23), the confirmed objective response rate (ORR) at week 24, the primary endpoint of the study, was 47.8% (95% CI: 26.8 – 69.4) based on investigator assessment and 52.2% based on independent radiologic review (IRR) (95% CI: 30.6 – 73.2), all of which were partial responses. No new safety signals were found and toxicities were managed with dose interruption, modification or discontinuation. Lenvima and KEYTRUDA are not approved for use in combination, and neither drug is approved for the treatment of endometrial cancer. These results will be presented today at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago during the Gynecologic Cancer Poster Session from 1:15-4:45 p.m. CT (Abstract No. 5598).
Metastatic endometrial cancer is a difficult-to-treat form of the disease as response rates for patients who have received first-line treatment are often low. Beyond chemotherapy and hormone therapy, there are no FDA-approved therapies for these patients.
“We are encouraged by the results of this study in which nearly half of the patients who have received prior systemic therapy for the treatment of recurrent advanced or metastatic endometrial cancer responded to this combination therapy,” said Vicky Makker, MD, gynecologic medical oncologist, Memorial Sloan Kettering Cancer Center and lead investigator. “Women whose endometrial cancer has recurred are in need of additional therapeutic options, and we look forward to learning more regarding the potential of this combination regimen for these women.”
Secondary endpoints include progression-free survival (PFS), disease control rate (DCR; partial response and stable disease), clinical benefit rate (CBR; partial response and durable stable disease), duration of response (DOR) and safety and tolerability. Median PFS was 9.7 months (95% CI: 4.2 – NE) based on investigator assessment and was not reached by IRR. DCR was 95.7% (95% CI: 78.1 – 99.9) based on investigator assessment and 91.3% (95% CI: 72.0 – 98.9) based on IRR. CBR was 73.9% (95% CI: 51.6 – 89.8) based on investigator assessment and 65.2% (95% CI: 42.7 – 83.6) based on IRR. Median DOR was not reached at the time of analysis (2.6 – NE). Tumor shrinkage was observed regardless of MSI (microsatellite instability) status. All patients had a treatment-emergent adverse event (TEAE) and a treatment-related TEAE. The most common TEAEs for the combination regimen were hypertension, fatigue, diarrhea, nausea, and arthralgia. Ten patients experienced serious TEAEs; the only serious TEAE experienced by more than one patient was hypertension.
“Given the response rates demonstrated in this study, we are enthusiastic about continuing further research of this immuno-targeted therapy combination regimen in women previously treated for metastatic endometrial cancer,” said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai.
“Little progress has been made in bringing forward new approaches for metastatic endometrial cancer. The interim results of the combination of these two mechanisms are encouraging and further support the potential for pembrolizumab and lenvatinib to help women with this aggressive and difficult-to-treat cancer,” said Dr. Eric Rubin, vice president and therapeutic area head, oncology early stage development, Merck Research Laboratories.
Lenvima (lenvatinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Lenvima is also indicated in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. This release discusses an investigational use for FDA-approved products. Lenvima is not approved for use in combination with KEYTRUDA. This release is not intended to convey any conclusions about efficacy or safety of lenvatinib, pembrolizumab or any combination of these two agents. There is no guarantee that any investigational uses of such FDA-approved products will successfully complete clinical development or gain FDA approval.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, NJ, USA.
About Study 111
Study 111 is a multicenter, open-label Phase 1b/2 basket trial of the combination of lenvatinib (20 mg/day) with pembrolizumab (200 mg intravenously every 3 weeks) in patients with selected solid tumors. The primary endpoint of the Phase 1b study was to determine the maximum tolerated dose of pembrolizumab and lenvatinib in combination. The primary endpoint of the Phase 2 study is investigator-assessed ORR based on immune-related RECIST at week 24. The secondary endpoints include progression-free survival, duration of response, disease control rate, and clinical benefit rate. Twenty three patients with previously treated metastatic endometrial cancer were evaluated in the endometrial cohort. The study is being conducted under an existing clinical trial collaboration agreement between the two companies.
About Endometrial Cancer
Endometrial cancer occurs in the tissues of the endometrium, which is the inner layer or inner lining of the uterus. In the United States, endometrial cancer is the most common cancer of the female reproductive system. This year approximately 61,300 new cases of endometrial cancer will occur, and an estimated 10,900 women will die from this disease. Nine percent of women have metastatic disease at diagnosis and the 5-year relative survival rate for these women is just over 16%.
About Lenvima® (lenvatinib)
Lenvima® (lenvatinib) is a kinase inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.
Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thought to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
SOURCE: Eisai
Post Views: 34
– Interim results of first evaluable cohort (metastatic endometrial cancer) of Study 111, the Phase 1b/2 trial evaluating lenvatinib in combination with pembrolizumab in selected solid tumors, to be presented at 2017 ASCO Annual Meeting
WOODCLIFF LAKE, NJ, USA I June 3, 2017 I Eisai Inc. today announced interim results from the first evaluable cohort of Study 111, a Phase 1b/2 study investigating lenvatinib (marketed as Lenvima®), a multiple receptor tyrosine kinase inhibitor, in combination with Merck’s (known as MSD outside the United States and Canada) pembrolizumab (marketed as KEYTRUDA®), an anti-PD-1 therapy, in patients with selected solid tumors. In this cohort of previously treated patients (median = 2 prior therapies) with metastatic endometrial cancer (n=23), the confirmed objective response rate (ORR) at week 24, the primary endpoint of the study, was 47.8% (95% CI: 26.8 – 69.4) based on investigator assessment and 52.2% based on independent radiologic review (IRR) (95% CI: 30.6 – 73.2), all of which were partial responses. No new safety signals were found and toxicities were managed with dose interruption, modification or discontinuation. Lenvima and KEYTRUDA are not approved for use in combination, and neither drug is approved for the treatment of endometrial cancer. These results will be presented today at the 2017 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago during the Gynecologic Cancer Poster Session from 1:15-4:45 p.m. CT (Abstract No. 5598).
Metastatic endometrial cancer is a difficult-to-treat form of the disease as response rates for patients who have received first-line treatment are often low. Beyond chemotherapy and hormone therapy, there are no FDA-approved therapies for these patients.
“We are encouraged by the results of this study in which nearly half of the patients who have received prior systemic therapy for the treatment of recurrent advanced or metastatic endometrial cancer responded to this combination therapy,” said Vicky Makker, MD, gynecologic medical oncologist, Memorial Sloan Kettering Cancer Center and lead investigator. “Women whose endometrial cancer has recurred are in need of additional therapeutic options, and we look forward to learning more regarding the potential of this combination regimen for these women.”
Secondary endpoints include progression-free survival (PFS), disease control rate (DCR; partial response and stable disease), clinical benefit rate (CBR; partial response and durable stable disease), duration of response (DOR) and safety and tolerability. Median PFS was 9.7 months (95% CI: 4.2 – NE) based on investigator assessment and was not reached by IRR. DCR was 95.7% (95% CI: 78.1 – 99.9) based on investigator assessment and 91.3% (95% CI: 72.0 – 98.9) based on IRR. CBR was 73.9% (95% CI: 51.6 – 89.8) based on investigator assessment and 65.2% (95% CI: 42.7 – 83.6) based on IRR. Median DOR was not reached at the time of analysis (2.6 – NE). Tumor shrinkage was observed regardless of MSI (microsatellite instability) status. All patients had a treatment-emergent adverse event (TEAE) and a treatment-related TEAE. The most common TEAEs for the combination regimen were hypertension, fatigue, diarrhea, nausea, and arthralgia. Ten patients experienced serious TEAEs; the only serious TEAE experienced by more than one patient was hypertension.
“Given the response rates demonstrated in this study, we are enthusiastic about continuing further research of this immuno-targeted therapy combination regimen in women previously treated for metastatic endometrial cancer,” said Alton Kremer, MD, PhD, Chief Clinical Officer and Chief Medical Officer, Oncology Business Group at Eisai.
“Little progress has been made in bringing forward new approaches for metastatic endometrial cancer. The interim results of the combination of these two mechanisms are encouraging and further support the potential for pembrolizumab and lenvatinib to help women with this aggressive and difficult-to-treat cancer,” said Dr. Eric Rubin, vice president and therapeutic area head, oncology early stage development, Merck Research Laboratories.
Lenvima (lenvatinib) is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Lenvima is also indicated in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. This release discusses an investigational use for FDA-approved products. Lenvima is not approved for use in combination with KEYTRUDA. This release is not intended to convey any conclusions about efficacy or safety of lenvatinib, pembrolizumab or any combination of these two agents. There is no guarantee that any investigational uses of such FDA-approved products will successfully complete clinical development or gain FDA approval.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Kenilworth, NJ, USA.
About Study 111
Study 111 is a multicenter, open-label Phase 1b/2 basket trial of the combination of lenvatinib (20 mg/day) with pembrolizumab (200 mg intravenously every 3 weeks) in patients with selected solid tumors. The primary endpoint of the Phase 1b study was to determine the maximum tolerated dose of pembrolizumab and lenvatinib in combination. The primary endpoint of the Phase 2 study is investigator-assessed ORR based on immune-related RECIST at week 24. The secondary endpoints include progression-free survival, duration of response, disease control rate, and clinical benefit rate. Twenty three patients with previously treated metastatic endometrial cancer were evaluated in the endometrial cohort. The study is being conducted under an existing clinical trial collaboration agreement between the two companies.
About Endometrial Cancer
Endometrial cancer occurs in the tissues of the endometrium, which is the inner layer or inner lining of the uterus. In the United States, endometrial cancer is the most common cancer of the female reproductive system. This year approximately 61,300 new cases of endometrial cancer will occur, and an estimated 10,900 women will die from this disease. Nine percent of women have metastatic disease at diagnosis and the 5-year relative survival rate for these women is just over 16%.
About Lenvima® (lenvatinib)
Lenvima® (lenvatinib) is a kinase inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for patients with advanced RCC following one prior anti-angiogenic therapy.
Lenvatinib, discovered and developed by Eisai, is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1-3. Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. The combination of lenvatinib and everolimus showed increased anti-angiogenic and anti-tumor activity as demonstrated by decreased human endothelial cell proliferation, tube formation, and VEGF signaling in vitro and tumor volume in mouse xenograft models of human renal cell cancer greater than each drug alone.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thought to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US.
SOURCE: Eisai
Post Views: 34
