On May 16, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the Phase 2b ECLIPSE trial did not meet the primary endpoint of an improvement in overall survival for patients with pancreatic cancer who had failed at least two prior therapies in the metastatic setting (Press release, Aduro BioTech, MAY 16, 2016, View Source [SID:1234512424]).

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Median overall survival (MOS) in this third-line and greater setting was 3.8 months for patients treated with the immunotherapy regimen of CRS-207 and GVAX Pancreas, 5.4 months for patients treated with CRS-207 alone and 4.6 months for patients administered chemotherapy. There were no unexpected safety findings with the combination of CRS-207 and GVAX Pancreas or CRS-207 alone, and the immunotherapies were generally well tolerated. Management will review these results in more detail on a conference call today at 6:00 am Pacific Time. Full study findings will be presented at a future scientific congress.

"This is an unexpected outcome, and we are disappointed particularly for the pancreatic cancer patients who are in need of additional treatment options," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "We would like to thank the patients and their families, investigators and staff involved in this Phase 2b trial for their support and participation in this study. While we are well aware of the very difficult-to-treat nature of late-stage metastatic pancreatic cancer, we are surprised by the divergence of these data from the results of our Phase 2a study. At the same time, we continue to look forward to the interim results later this year from our ongoing STELLAR trial, which is evaluating CRS-207 and GVAX Pancreas with and without the anti-PD1 checkpoint inhibitor nivolumab as a second-line therapy for patients with metastatic pancreatic cancer. We believe the scientific rationale for combining CRS-207 with a checkpoint inhibitor is compelling. Additionally, as a company, we are very well-positioned with a strong cash position and three differentiated, potentially synergistic immunotherapy platforms comprising our LADD, STING pathway activator and B-select monoclonal antibody programs."

"In the overall survival analysis, we were intrigued by activity seen with CRS-207 as a single-agent. While the median duration of 5.4 months appears greater for CRS-207, the overall survival curve of CRS-207 alone was comparable to overall survival seen with chemotherapy. Of note, due to a disproportionately high dropout rate in the single-agent chemotherapy arm, most of these patients instead received a variety of combination treatments, including chemotherapies, immunotherapies and targeted therapies," said Dirk Brockstedt, Ph.D., executive vice president, research and development for Aduro.

Andrew Ko, M.D., professor, Department of Medicine (hematology/oncology) at University of California San Francisco added, "As the scientific community continues to discover the optimal approach towards enlisting the power of the immune system in the fight against elusive diseases such as pancreatic cancer, I applaud Aduro for their pioneering contributions to the field. Immunotherapy is ushering in a new era in our fundamental understanding of human biology, and although the results are not what we had hoped for from this well-executed trial, they will provide important information for changing the treatment paradigm in the future."

About ECLIPSE
The ECLIPSE trial (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting) enrolled 303 adults with previously-treated metastatic pancreatic cancer in over 20 clinical trial sites in the U.S. and Canada. The open-label randomized, controlled 3-arm trial evaluated the safety, immune response and efficacy of the combination immunotherapy of CRS-207 with GVAX Pancreas (with low-dose cyclophosphamide (CY)) and CRS-207 alone, compared to chemotherapy. The primary endpoint of the trial was overall survival. Secondary endpoints included evaluation of clinical and immune response and safety.

CRS-207 has been engineered to induce an immune response to the tumor-associated antigen mesothelin. Mesothelin is over-expressed in many cancers, including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.

About STELLAR
The randomized, controlled STELLAR trial (Safety and Therapeutic Efficacy of Live-attenuated Listeria/GVAX with Anti-PD1 Regimen) is expected to enroll approximately 102 adults with metastatic pancreatic cancer who have received one prior chemotherapy to treat metastatic disease. The trial includes two arms: Arm A with CRS-207 and GVAX Pancreas as well as the checkpoint inhibitor, nivolumab, and Arm B with CRS-207 and GVAX Pancreas. The primary objective of this study is to compare the overall survival (OS) of patients in Arm A and Arm B. Secondary endpoints include evaluation of clinical and immune response and safety. For more information, please visit ClinicalTrials.gov (Identifier: NCT02243371).

About Metastatic Pancreatic Cancer
Each year, it is estimated that more than 337,000 people worldwide are diagnosed with pancreatic cancer and more than 330,000 people die from the disease. Despite steady advances in diagnosis and treatment that have dramatically improved outcomes and extended survival in many tumor types, pancreatic cancer remains one of the world’s deadliest cancers, with a five-year survival rate of eight percent. While pancreatic cancer is the eleventh most common cancer in the United States, it is now the third leading cause of cancer-related death.I

Most often diagnosed when it has already metastasized (or spread) to other parts of the body, unresectable (not able to be surgically removed) pancreatic cancer is highly resistant to conventional treatments, including chemotherapy and radiation. It is rapidly fatal, often within months of diagnosis. The need for new, more effective treatments for this patient population has ignited interest in the potential of immunotherapies to engage the patient’s own immune system to extend survival.

On May 16, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that its U.S. subsidiary Eisai Inc. has received approval from the U.S. Food and Drug Administration (FDA) for an additional indication for Eisai’s in-house developed novel anticancer agent Lenvima (lenvatinib mesylate) in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy (Press release, Eisai, MAY 16, 2016, View Source [SID:1234512409]).

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This is the only combination regimen to significantly prolong progression-free survival (PFS) when compared with a standard of care in patients with advanced renal cell carcinoma following prior anti-angiogenic therapy. Lenvima was designated as a Breakthrough Therapy by the FDA and also received a Priority Review, with approval obtained approximately six months after application submission.

The approval was based on a Phase II clinical study (Study 205)1 that compared the safety and efficacy of Lenvima alone, and in combination with everolimus, in patients with unresectable advanced or metastatic renal cell carcinoma following one prior vascular endothelial growth factor-targeted therapy. From the results of the study, the group who received the combination of Lenvima plus everolimus demonstrated a significant extension in PFS, the study’s primary endpoint, as well as a higher objective response rate compared to the everolimus alone group. The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue.

The most common TEAEs of Grade 3 or higher were diarrhea, hypertension and fatigue. The number of patients with kidney cancer in the United States is estimated to be approximately 58,000, 2 and renal cell carcinoma comprises more than 90% of all malignancies of the kidney.3 For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment is molecular targeted drug therapy, however with low 5-year survival rates, this is a disease with significant unmet medical need.

Lenvima was first approved for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer in the United States in February 2015, and has since been approved for thyroid cancer in over 40 countries including Japan, in Europe, South Korea and Canada. A new drug application seeking approval for an indication covering advanced or metastatic renal cell carcinoma submitted in Europe in January 2016 is under review, and Eisai intends to discuss further steps regarding submission strategies for this potential indication with the regulatory authorities in Japan as well. Furthermore, Eisai is conducting clinical studies of Lenvima in several other tumor types including a Phase III study of the agent in hepatocellular carcinoma.

Through this additional approval, Eisai is committed to maximizing the clinical value as well as exploring the potential clinical benefits of Lenvima in order to address the diverse needs of, and further contribute to, patients with cancer and their families.

About Lenvima (lenvatinib mesylate)
Lenvima is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors (VEGFR1, VEGFR2 and VEGFR3) and fibroblast growth factor (FGF) receptors (FGFR1, FGFR2, FGFR3 and FGFR4) in addition to other proangiogenic and oncogenic pathway-related RTKs (including the platelet-derived growth factor (PDGF) receptor PDGFRα; KIT; and RET) involved in tumor proliferation.

Currently, Eisai has obtained approval for Lenvima as a treatment for refractory thyroid cancer in over 40 countries including in the United States, Japan, Europe, Korea and Canada, and is undergoing regulatory review throughout the world including in Asia, Russia, Australia, Brazil and Mexico. Specifically, Eisai has obtained approval for the agent indicated in the United States for treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer, in Japan for the treatment of unresectable thyroid cancer, and in Europe for the treatment of adult patients with progressive, locally advanced or metastatic differentiated (papillary, follicular, Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine, respectively.

Lenvima is now also approved for an additional indication in the United States in combination with everolimus for the treatment of patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. A new drug application seeking approval for an indication covering advanced or metastatic renal cell carcinoma submitted in Europe in January 2016 is under review, and Eisai intends to discuss further steps regarding submission strategies for this potential indication with the regulatory authorities in Japan.
Meanwhile, Eisai is conducting clinical studies of Lenvima in several other tumor types such as hepatocellular carcinoma (Phase III), endometrial carcinoma (Phase II), biliary tract cancer (Phase II), and in combination with an immune checkpoint inhibitor (Phase Ib/II).

About the Phase II Clinical Study (Study 205)1
Study 205 was a multicenter, randomized, open-label study of the combination of Lenvima (18 mg) plus everolimus (5 mg), Lenvima alone (24 mg), and everolimus alone (10 mg) in patients with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted therapy, and was conducted in Europe and the United States. 153 patients were randomized in a 1:1:1 ratio to one of three treatment arms to compare the efficacy and safety of these three regimens.

From the results of the study, the combination of Lenvima plus everolimus group demonstrated a significant extension in the study’s primary endpoint of progression free survival (PFS) compared to the everolimus alone group (median PFS for the Lenvima plus everolimus group: 14.6 months vs median PFS for the everolimus alone group: 5.5 months; Hazard Ratio (HR) 0.40 [95% CI: 0.24-0.68], p=0.0005). Additionally, median PFS for the Lenvima alone group was 7.4 months, demonstrating an extension in PFS compared to the everolimus alone group (HR: 0.61 [95% CI: 0.38-0.98]).

The study also assessed objective response rate (ORR) and overall survival (OS) as secondary endpoints. Regarding ORR, both the Lenvima plus everolimus group and the Lenvima alone group showed an improvement in ORR compared to the everolimus alone group (Lenvima plus everolimus: 43%, Lenvima alone: 27%, everolimus alone: 6%). Furthermore, regarding OS, an updated analysis carried out in December 2014 suggested that Lenvima plus everolimus extends OS compared to everolimus alone (HR 0.51 [95% CI=0.30-0.88]).

The most common treatment-emergent adverse events (TEAEs) reported in the lenvatinib plus everolimus group were diarrhea, decreased appetite and fatigue. The most common TEAEs of Grade 3 or higher were diarrhea, hypertension and fatigue.
For further information on Lenvima in the United States, including Important Safety Information (ISI), please visit the Lenvima product website (View Source).

About Renal Cell Carcinoma
The number of patients with renal cancer was estimated to be approximately 338,000 worldwide, including approximately 58,000 in the United States, 115,000 in Europe and 17,000 in Japan.2 Renal cell carcinoma comprises more than 90% of all malignancies of the kidney, 3 and occurs when malignant cells are found in the lining of the tubules of the kidney. The incidence of renal cell carcinoma in people aged in their late 50s is rising, and is more likely to affect men than women. For advanced or metastatic renal cell carcinoma that is difficult to treat with surgery, the standard treatment method is molecular targeted drug therapy, however with low 5-year survival rates, this is a disease with significant unmet medical need.