First Randomized Study To Evaluate IMLYGIC® (Talimogene Laherparepvec), An Oncolytic Viral Therapy, In Combination With A Checkpoint Inhibitor Published In The Journal Of Clinical Oncology

Results Demonstrated a Doubling of Objective Response Rate Compared to Ipilimumab Alone in Unresectable Advanced Melanoma

Responses Were Not Limited to Injected Lesions and Favored the Combination Arm Across Subsets of Disease

THOUSAND OAKS, CA, USA I October 5, 2017 I Amgen (NASDAQ: AMGN) today announced that the Journal of Clinical Oncology has published positive results from the IMLYGIC® (talimogene laherparepvec) Phase 2 '264 study. The study met its primary endpoint of objective response rate (ORR), demonstrating that IMLYGIC in combination with YERVOY® (ipilimumab) more than doubled ORR, defined as the proportion of patients with tumor size reduction, compared to ipilimumab alone in patients with unresectable stage IIIB-IV melanoma (39 percent versus 18 percent; 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 ipilimumab alone (13 percent versus 7 percent).

"Advanced melanoma is highly aggressive and can require multiple treatment approaches over the course of the disease," said Jason Chesney, M.D., lead author of the '264 study and director of the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky. "Results from the study found that administration of IMLYGIC in combination with ipilimumab led to greater efficacy versus ipilimumab alone in both uninjected and visceral lesions. These data show that this combination of a checkpoint inhibitor plus IMLYGIC demonstrated a synergistic clinical effect and enhanced anti-tumor immune response in patients with metastatic melanoma."

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 ipilimumab'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.

Melanoma is one of the most dangerous types of skin cancers, especially when it spreads to other parts of the body.1 The study showed that responses occurred in both injected and uninjected lesions, including visceral lesions, demonstrating a systemic anti-tumor response. Thirty-one (32 percent) and 22 (22 percent) of the patients were shown to have visceral disease at baseline in the combination and ipilimumab arms, respectively. Of these patients, 16 (52 percent) in the combination arm and five (23 percent) in the ipilimumab arm were observed to have a decrease in visceral lesion tumor burden. Patients in the combination arm also experienced a median progression-free survival (PFS) of 8.2 months (median follow up 68 weeks) versus 6.4 months in the ipilimumab arm. The effect was not statistically significant (HR=0.83, 95 percent CI: 0.56, 1.23; p=0.35); however, the PFS analysis was not event-driven and is still ongoing. Evaluation of overall survival (OS) is ongoing and continues to be monitored.

The most common adverse events in the IMLYGIC plus ipilimumab arm compared to the ipilimumab alone arm were fatigue (59 percent versus 42 percent, respectively), chills (53 percent versus 3 percent, respectively), diarrhea (42 percent versus 35 percent, respectively), pruritus (40 percent versus 36 percent, respectively), rash (39 percent versus 28 percent, respectively) and nausea (38 percent versus 24 percent, respectively).

"IMLYGIC is the first and only approved oncolytic viral therapy in the U.S. and Europe, reinforcing Amgen's leadership and commitment to developing innovative therapies for difficult-to-treat cancers," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The data published today in the Journal of Clinical Oncology supports the scientific hypothesis behind the combination of IMLYGIC with an immune checkpoint inhibitor. We are excited about the promise of our diverse immuno-oncology pipeline that looks at combinations that may be effective in stimulating an immune attack on cancer cells."

In the study, response rate was also higher in the combination arm across subsets of the disease. ORR for patients with stage IIIB/IIIC/IVM1a disease was 44 percent in the combination arm and 19 percent in the ipilimumab arm (overall response [OR]=3.3, 95 percent CI: 1.4, 7.8; p=0.007). In patients with stage IVM1b/IVM1c disease, ORR was 33 percent and 16 percent, respectively (OR=2.6, 95 percent CI: 0.9, 7.0; p=0.09). Among BRAF wild-type patients, ORR was 42 percent in the combination arm versus 10 percent in the ipilimumab arm (OR=6.5, 95 percent CI: 2.4, 17.4; p<0.0001). In patients with BRAF-mutant tumors, which comprised a minority of each arm at 35 (36 percent) and 34 (34 percent) for the combination and ipilimumab arms respectively, ORR was 34 percent in the combination arm versus 32 percent in the ipilimumab arm (OR=1.1, 95 percent CI: 0.4, 3.0; p=1.0). The disease control rate (DCR) was 58 percent in the combination arm and 42 percent in the ipilimumab arm (OR=1.9, 95 percent CI: 1.1, 3.4; p=0.033). DCR in all subgroups, with the exception of patients with BRAF mutations, favored the combination arm.

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 ipilimumab compared to ipilimumab 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, DCR, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus ipilimumab arm and 100 in the ipilimumab 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.2,3 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.1 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 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

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