First Randomized Study to Evaluate the Combination of IMLYGIC, an Oncolytic Viral Therapy, With a Checkpoint Inhibitor
Data Demonstrate IMLYGIC in Combination With YERVOY® (Ipilimumab) Doubled Objective Response Rate in Unresectable Advanced Melanoma
Responses Not Limited to Injected Lesions; 50 Percent or Higher Reduction in Visceral Lesion Size Occurred More Frequently in Patients in the Combination Arm
THOUSAND OAKS, CA, USA I June 3, 2017 I Amgen (NASDAQ:AMGN) today announced new data from the Phase 2 ‘264 study that demonstrated IMLYGIC® (talimogene laherparepvec) in combination with the immune checkpoint inhibitor YERVOY® (ipilimumab)* more than doubled objective response rate (ORR), defined as the proportion of patients with tumor size reduction, compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma, meeting the primary endpoint of the study. The analysis showed that 38.8 percent of patients treated with IMLYGIC plus YERVOY achieved an objective response versus 18 percent of patients treated with YERVOY alone (odds ratio=2.9, 95 percent CI: 1.5, 5.5; p=0.002). Patients in the combination arm also experienced nearly double the complete response rate compared to YERVOY alone (13.3 percent versus 7 percent). The results were presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO).
“Metastatic melanoma continues to be one of the most difficult-to-treat and aggressive cancers,” said Jason Chesney, M.D., ‘264 study investigator and acting director of the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky. “The results from this study demonstrate the potential of combining the complementary mechanisms of action of an oncolytic viral immunotherapy and a checkpoint inhibitor to enhance anti-tumor effect in patients with advanced melanoma.”
Responses were not limited to injected lesions. Among patients with visceral disease treated with IMLYGIC plus YERVOY, 35 percent had a reduction in size of visceral lesions by at least 50 percent. The rate was 14 percent in patients in the YERVOY arm. Patients in the IMLYGIC plus YERVOY arm experienced a median progression-free survival (PFS) of 8.2 months (median follow up 68 weeks) versus 6.4 months in the YERVOY arm. The effect was not statistically significant (HR=0.83, 95 percent CI; p=0.35); however, the PFS analysis was not event-driven and is still ongoing, with only approximately 50 percent of PFS events reported at this time.
“Patients with metastatic melanoma are in need of innovative, effective treatment options that can improve response rates and help prevent disease recurrence,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These are the first randomized, controlled, Phase 2 data demonstrating clear efficacy and safety of an oncolytic virus with a checkpoint inhibitor. We are excited to be exploring IMLYGIC with PD-1 and PDL-1 checkpoint inhibitors as well.”
The most common adverse events in the IMLYGIC plus YERVOY arm were fatigue (59 percent versus 42 percent, respectively), chills (53 percent versus 3 percent, respectively) and diarrhea (42 percent versus 35 percent, respectively). Evaluation of overall survival (OS) is ongoing and continues to be monitored. IMLYGIC is designed to rupture cancer cells causing the release of tumor-derived antigens, which along with granulocyte-macrophage colony-stimulating factor (GM-CSF), may help to initiate an anti-tumor immune response. However, the exact mechanism of action is unknown. This may be complementary to YERVOY’s mechanism of action, as the blockade of cytotoxic T-lymphocyte-associated antigen-4 has been shown to augment activation and proliferation of tumor infiltrating T-effector cells.
In addition, these results follow the presentation of new interim data from a Phase 2 biomarker study, which evaluated CD8+ T cell density in biopsies from patients with unresectable stage IIIB-IVM1c melanoma treated with IMLYGIC. These data were presented at the 13th Congress of the European Association of Dermato Oncology in Athens, Greece. The study demonstrated a significant four-fold mean increase in intratumoral CD8+ cell density in uninjected melanoma lesions among 32 matched biopsy pairs collected at baseline and after two doses of IMLYGIC. The response rate was consistent with other IMLYGIC monotherapy studies and the adverse events profile was consistent with the known safety profile of IMLYGIC.
About the ‘264 Study
The ‘264 study is a Phase 1b/2, multicenter, open-label trial evaluating the safety and efficacy of IMLYGIC in combination with YERVOY compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma. The primary endpoint of the Phase 2 portion of study is ORR. Secondary endpoints include duration of response, disease control rate, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus YERVOY arm and 100 in the YERVOY arm.
About Metastatic Melanoma
Melanoma remains a significant public health concern across the globe. Unlike some other cancers, melanoma incidence rates have doubled in the past 40 years, with 132,000 cases occurring worldwide each year.1,2 Melanoma is more dangerous than other skin cancers, especially when it spreads to other parts of the body, which is referred to as metastatic disease.3 The overall five-year risk of relapse after surgery increases as disease stage advances, from 48 percent for stage IIIA to 85 percent for stage IIIC.4 Risk of recurrence is even higher for patients in stage IV undergoing surgery, with 91 percent experiencing relapse.5 Despite new options, additional treatments are needed – particularly for patients with metastatic disease.
About IMLYGIC® (talimogene laherparepvec)
IMLYGIC® (talimogene laherparepvec) is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve OS or have an effect on visceral metastases.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
SOURCE: Amgen
Post Views: 27
First Randomized Study to Evaluate the Combination of IMLYGIC, an Oncolytic Viral Therapy, With a Checkpoint Inhibitor
Data Demonstrate IMLYGIC in Combination With YERVOY® (Ipilimumab) Doubled Objective Response Rate in Unresectable Advanced Melanoma
Responses Not Limited to Injected Lesions; 50 Percent or Higher Reduction in Visceral Lesion Size Occurred More Frequently in Patients in the Combination Arm
THOUSAND OAKS, CA, USA I June 3, 2017 I Amgen (NASDAQ:AMGN) today announced new data from the Phase 2 ‘264 study that demonstrated IMLYGIC® (talimogene laherparepvec) in combination with the immune checkpoint inhibitor YERVOY® (ipilimumab)* more than doubled objective response rate (ORR), defined as the proportion of patients with tumor size reduction, compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma, meeting the primary endpoint of the study. The analysis showed that 38.8 percent of patients treated with IMLYGIC plus YERVOY achieved an objective response versus 18 percent of patients treated with YERVOY alone (odds ratio=2.9, 95 percent CI: 1.5, 5.5; p=0.002). Patients in the combination arm also experienced nearly double the complete response rate compared to YERVOY alone (13.3 percent versus 7 percent). The results were presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO).
“Metastatic melanoma continues to be one of the most difficult-to-treat and aggressive cancers,” said Jason Chesney, M.D., ‘264 study investigator and acting director of the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky. “The results from this study demonstrate the potential of combining the complementary mechanisms of action of an oncolytic viral immunotherapy and a checkpoint inhibitor to enhance anti-tumor effect in patients with advanced melanoma.”
Responses were not limited to injected lesions. Among patients with visceral disease treated with IMLYGIC plus YERVOY, 35 percent had a reduction in size of visceral lesions by at least 50 percent. The rate was 14 percent in patients in the YERVOY arm. Patients in the IMLYGIC plus YERVOY arm experienced a median progression-free survival (PFS) of 8.2 months (median follow up 68 weeks) versus 6.4 months in the YERVOY arm. The effect was not statistically significant (HR=0.83, 95 percent CI; p=0.35); however, the PFS analysis was not event-driven and is still ongoing, with only approximately 50 percent of PFS events reported at this time.
“Patients with metastatic melanoma are in need of innovative, effective treatment options that can improve response rates and help prevent disease recurrence,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “These are the first randomized, controlled, Phase 2 data demonstrating clear efficacy and safety of an oncolytic virus with a checkpoint inhibitor. We are excited to be exploring IMLYGIC with PD-1 and PDL-1 checkpoint inhibitors as well.”
The most common adverse events in the IMLYGIC plus YERVOY arm were fatigue (59 percent versus 42 percent, respectively), chills (53 percent versus 3 percent, respectively) and diarrhea (42 percent versus 35 percent, respectively). Evaluation of overall survival (OS) is ongoing and continues to be monitored. IMLYGIC is designed to rupture cancer cells causing the release of tumor-derived antigens, which along with granulocyte-macrophage colony-stimulating factor (GM-CSF), may help to initiate an anti-tumor immune response. However, the exact mechanism of action is unknown. This may be complementary to YERVOY’s mechanism of action, as the blockade of cytotoxic T-lymphocyte-associated antigen-4 has been shown to augment activation and proliferation of tumor infiltrating T-effector cells.
In addition, these results follow the presentation of new interim data from a Phase 2 biomarker study, which evaluated CD8+ T cell density in biopsies from patients with unresectable stage IIIB-IVM1c melanoma treated with IMLYGIC. These data were presented at the 13th Congress of the European Association of Dermato Oncology in Athens, Greece. The study demonstrated a significant four-fold mean increase in intratumoral CD8+ cell density in uninjected melanoma lesions among 32 matched biopsy pairs collected at baseline and after two doses of IMLYGIC. The response rate was consistent with other IMLYGIC monotherapy studies and the adverse events profile was consistent with the known safety profile of IMLYGIC.
About the ‘264 Study
The ‘264 study is a Phase 1b/2, multicenter, open-label trial evaluating the safety and efficacy of IMLYGIC in combination with YERVOY compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma. The primary endpoint of the Phase 2 portion of study is ORR. Secondary endpoints include duration of response, disease control rate, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus YERVOY arm and 100 in the YERVOY arm.
About Metastatic Melanoma
Melanoma remains a significant public health concern across the globe. Unlike some other cancers, melanoma incidence rates have doubled in the past 40 years, with 132,000 cases occurring worldwide each year.1,2 Melanoma is more dangerous than other skin cancers, especially when it spreads to other parts of the body, which is referred to as metastatic disease.3 The overall five-year risk of relapse after surgery increases as disease stage advances, from 48 percent for stage IIIA to 85 percent for stage IIIC.4 Risk of recurrence is even higher for patients in stage IV undergoing surgery, with 91 percent experiencing relapse.5 Despite new options, additional treatments are needed – particularly for patients with metastatic disease.
About IMLYGIC® (talimogene laherparepvec)
IMLYGIC® (talimogene laherparepvec) is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve OS or have an effect on visceral metastases.
About Amgen’s Commitment to Oncology
Amgen Oncology is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen’s supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people’s lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world’s leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
SOURCE: Amgen
Post Views: 27
