KEYTRUDA plus chemotherapy reduced risk of disease progression or death by 46% in patients whose cancer was mismatch repair proficient (pMMR) and by 70% in patients whose cancer was mismatch repair deficient (dMMR), compared to chemotherapy alone
Results from Phase 3 NRG-GY018 trial to be presented at Society of Gynecologic Oncology (SGO) 2023 Annual Meeting and published simultaneously in New England Journal of Medicine
RAHWAY, NJ, USA I March 27, 2023 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 NRG‑GY018 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (carboplatin and paclitaxel) then continued as a single agent every six weeks for up to 14 cycles for the first-line treatment of patients with stage III-IV or recurrent endometrial carcinoma whose cancer was either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR). Results from the trial showed the KEYTRUDA regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients, regardless of mismatch repair status. These late-breaking data are being presented for the first time during a scientific plenary at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (abstract #338166) and are also being simultaneously published in the New England Journal of Medicine. The results are being discussed with regulatory authorities worldwide.
In the pMMR cohort of 591 evaluable patients, after a median follow-up of 7.9 months, the KEYTRUDA regimen significantly reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.41-0.71]; p<0.00001) compared to chemotherapy alone; median PFS was 13.1 months (95% CI, 10.5-18.8) for the KEYTRUDA regimen versus 8.7 months (95% CI, 8.4-10.7) for chemotherapy alone. In the dMMR cohort of 225 evaluable patients, after a median follow-up of 12 months, the KEYTRUDA regimen significantly reduced the risk of disease progression or death by 70% (HR=0.30 [95% CI, 0.19-0.48]; p<0.00001) compared to chemotherapy alone; median PFS was not reached (95% CI, 30.6-NR) for the KEYTRUDA regimen versus 7.6 months (95% CI, 6.4-9.9) for chemotherapy alone.
“Endometrial cancer is the most common type of gynecological cancer, and patients with advanced stage or recurrent disease face a poor prognosis with limited treatment options,” said Dr. Ramez Eskander, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center. “The significant improvement in progression-free survival regardless of mismatch repair status observed in this study demonstrates the potential of this pembrolizumab regimen to benefit these patients.”
The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Grade 3-5 adverse events (AEs) occurred in 55.1% of patients receiving the KEYTRUDA regimen and 45.3% of patients receiving chemotherapy alone in the pMMR cohort. In the dMMR cohort, Grade 3-5 AEs occurred in 63.3% of patients receiving the KEYTRUDA regimen and 47.2% of patients receiving chemotherapy alone. There were no KEYTRUDA-related AEs leading to death in either cohort.
“KEYTRUDA has become an important treatment option, both as monotherapy and in combination, in certain patients with advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for surgery or radiation,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Results from this trial show that KEYTRUDA plus chemotherapy, if approved, may represent an important new first-line immunotherapy option for patients with stage III-IV disease, and could extend the use of KEYTRUDA to more patients earlier in their treatment journey.”
This trial was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. NRG Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network (NCTN) Groups. Merck provided funding and support through a Cooperative Research and Development Agreement (CRADA) between Merck and NCI.
In the U.S., KEYTRUDA has two approved indications in endometrial cancer: in combination with LENVIMA® (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is pMMR, as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; and as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck has a comprehensive clinical development program in breast and gynecological (ovarian, cervical, and endometrial) cancers, comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In endometrial cancer, Merck is evaluating KEYTRUDA in first-line advanced endometrial cancer both as monotherapy (KEYNOTE-C93/ENGOT-en15/GOG-3064) and in combination with LENVIMA (LEAP-001/ENGOT-en9), as well as in the adjuvant setting (KEYNOTE-B21/ENGOT-en11/GOG-3053).
About NRG-GY018
NRG-GY018 is a randomized, blinded, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03914612) evaluating KEYTRUDA in combination with standard of care chemotherapy (paclitaxel and carboplatin) versus placebo plus standard of care chemotherapy for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate, duration of response and safety. The trial enrolled 816 patients who were randomized to receive KEYTRUDA plus chemotherapy every three weeks for approximately six cycles followed by KEYTRUDA as a single agent every six weeks for up to 14 cycles, or placebo plus chemotherapy. Enrolled patients were required to have MMR IHC testing prior to randomization; 591 patients were determined to have pMMR tumors, and 225 were determined to have dMMR tumors.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 66,000 new cases of uterine body cancer and approximately 13,000 deaths from the disease in 2023. Globally, endometrial cancer is the sixth most common cancer in women and 15th most common cancer overall.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (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 1,600 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
About LENVIMA® (lenvatinib); available as 10 mg and 4 mg capsules
LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases 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. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone.
LENVIMA® (lenvatinib) Indications in the U.S.
- For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
- In combination with pembrolizumab, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC)
- In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
- For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
- In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
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KEYTRUDA plus chemotherapy reduced risk of disease progression or death by 46% in patients whose cancer was mismatch repair proficient (pMMR) and by 70% in patients whose cancer was mismatch repair deficient (dMMR), compared to chemotherapy alone
Results from Phase 3 NRG-GY018 trial to be presented at Society of Gynecologic Oncology (SGO) 2023 Annual Meeting and published simultaneously in New England Journal of Medicine
RAHWAY, NJ, USA I March 27, 2023 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 NRG‑GY018 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with standard of care chemotherapy (carboplatin and paclitaxel) then continued as a single agent every six weeks for up to 14 cycles for the first-line treatment of patients with stage III-IV or recurrent endometrial carcinoma whose cancer was either mismatch repair proficient (pMMR) or mismatch repair deficient (dMMR). Results from the trial showed the KEYTRUDA regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for patients, regardless of mismatch repair status. These late-breaking data are being presented for the first time during a scientific plenary at the 2023 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer (abstract #338166) and are also being simultaneously published in the New England Journal of Medicine. The results are being discussed with regulatory authorities worldwide.
In the pMMR cohort of 591 evaluable patients, after a median follow-up of 7.9 months, the KEYTRUDA regimen significantly reduced the risk of disease progression or death by 46% (HR=0.54 [95% CI, 0.41-0.71]; p<0.00001) compared to chemotherapy alone; median PFS was 13.1 months (95% CI, 10.5-18.8) for the KEYTRUDA regimen versus 8.7 months (95% CI, 8.4-10.7) for chemotherapy alone. In the dMMR cohort of 225 evaluable patients, after a median follow-up of 12 months, the KEYTRUDA regimen significantly reduced the risk of disease progression or death by 70% (HR=0.30 [95% CI, 0.19-0.48]; p<0.00001) compared to chemotherapy alone; median PFS was not reached (95% CI, 30.6-NR) for the KEYTRUDA regimen versus 7.6 months (95% CI, 6.4-9.9) for chemotherapy alone.
“Endometrial cancer is the most common type of gynecological cancer, and patients with advanced stage or recurrent disease face a poor prognosis with limited treatment options,” said Dr. Ramez Eskander, principal investigator and gynecologic oncologist, University of California San Diego, Moores Cancer Center. “The significant improvement in progression-free survival regardless of mismatch repair status observed in this study demonstrates the potential of this pembrolizumab regimen to benefit these patients.”
The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Grade 3-5 adverse events (AEs) occurred in 55.1% of patients receiving the KEYTRUDA regimen and 45.3% of patients receiving chemotherapy alone in the pMMR cohort. In the dMMR cohort, Grade 3-5 AEs occurred in 63.3% of patients receiving the KEYTRUDA regimen and 47.2% of patients receiving chemotherapy alone. There were no KEYTRUDA-related AEs leading to death in either cohort.
“KEYTRUDA has become an important treatment option, both as monotherapy and in combination, in certain patients with advanced endometrial cancer who have progressed following prior systemic therapy and are not candidates for surgery or radiation,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Results from this trial show that KEYTRUDA plus chemotherapy, if approved, may represent an important new first-line immunotherapy option for patients with stage III-IV disease, and could extend the use of KEYTRUDA to more patients earlier in their treatment journey.”
This trial was sponsored by the U.S. National Cancer Institute (NCI), part of the National Institutes of Health. NRG Oncology designed and led the trial with funding from the NCI and participation from all the National Clinical Trials Network (NCTN) Groups. Merck provided funding and support through a Cooperative Research and Development Agreement (CRADA) between Merck and NCI.
In the U.S., KEYTRUDA has two approved indications in endometrial cancer: in combination with LENVIMA® (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is pMMR, as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation; and as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Merck has a comprehensive clinical development program in breast and gynecological (ovarian, cervical, and endometrial) cancers, comprised of more than 20 Merck-sponsored Phase 3 studies evaluating KEYTRUDA as monotherapy and in combination with other medicines. In endometrial cancer, Merck is evaluating KEYTRUDA in first-line advanced endometrial cancer both as monotherapy (KEYNOTE-C93/ENGOT-en15/GOG-3064) and in combination with LENVIMA (LEAP-001/ENGOT-en9), as well as in the adjuvant setting (KEYNOTE-B21/ENGOT-en11/GOG-3053).
About NRG-GY018
NRG-GY018 is a randomized, blinded, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03914612) evaluating KEYTRUDA in combination with standard of care chemotherapy (paclitaxel and carboplatin) versus placebo plus standard of care chemotherapy for the treatment of measurable stage III, IVA, IVB or recurrent endometrial cancer in pMMR and dMMR cohorts. The primary endpoint is PFS, and secondary endpoints include overall survival, objective response rate, duration of response and safety. The trial enrolled 816 patients who were randomized to receive KEYTRUDA plus chemotherapy every three weeks for approximately six cycles followed by KEYTRUDA as a single agent every six weeks for up to 14 cycles, or placebo plus chemotherapy. Enrolled patients were required to have MMR IHC testing prior to randomization; 591 patients were determined to have pMMR tumors, and 225 were determined to have dMMR tumors.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 66,000 new cases of uterine body cancer and approximately 13,000 deaths from the disease in 2023. Globally, endometrial cancer is the sixth most common cancer in women and 15th most common cancer overall.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (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 1,600 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Endometrial Carcinoma
KEYTRUDA, in combination with LENVIMA, is indicated for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
About LENVIMA® (lenvatinib); available as 10 mg and 4 mg capsules
LENVIMA, discovered and developed by Eisai, is a multiple receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases 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. In syngeneic mouse tumor models, the combination of lenvatinib with an anti-PD-1 monoclonal antibody decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity compared to either treatment alone.
LENVIMA® (lenvatinib) Indications in the U.S.
- For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)
- In combination with pembrolizumab, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC)
- In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior anti-angiogenic therapy
- For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)
- In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Please see Prescribing Information for LENVIMA (lenvatinib) at http://www.lenvima.com/pdfs/prescribing-information.pdf.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
Post Views: 212
