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ChemoCentryx Reports Initial Results from Ongoing Phase Ib Clinical Trial of CCX872 in Patients with Advanced Pancreatic Cancer

On September 1, 2016 ChemoCentryx, Inc., (Nasdaq:CCXI) reported initial 12 week overall response rate (ORR) results from an ongoing open label, single arm Phase Ib clinical trial with CCX872 in patients with advanced pancreatic cancer (Press release, ChemoCentryx, SEP 1, 2016, View Source [SID:1234514870]). CCX872 is a selective inhibitor of the chemokine receptor known as CCR2.

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The ongoing Phase Ib clinical study aims to evaluate the safety and effects of orally administered CCX872 when added to standard of care FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan and oxaliplatin) in patients with advanced non-resectable pancreatic cancer. Under the study protocol, patients may continue to receive CCX872 for an indefinite treatment period as long as there is no evidence of disease progression. The Company expects to report progression-free survival (PFS) by the end of 2016.

Patients enrolled in the study had advanced non-resectable pancreatic cancer (78% of patients having metastatic disease), and an Eastern Cooperative Oncology Group (ECOG) Performance Status score of less than or equal to 2. In order to assess the initial treatment effect of CCX872, the study provided for assessment of overall response rate (ORR) based on computerized tomography (CT) imaging following 12 weeks of treatment.

The pre-specified evaluable ORR population consists of all patients who have at least one post-baseline disease CT assessment. Response rate results at 12 weeks of treatment were as follows:

Pre-Specified Evaluable
Patient Population1
(N=41) ITT
Patient Population
(N=50)
Tumor control rate2 32/41 (78%) 32/50 (64%)
Overall response rate3 15/41 (37%) 15/50 (30%)
Stable disease 17/41 (41%) 17/50 (34%)
Progressive disease 9/41 (22%) 9/50 (18%)
Not evaluable4 9/50 (18%)
1 Pre-specified as the primary efficacy population = pre-defined as all patients who have a least one post baseline CT scan. ITT = all patients randomized, including those with no post baseline CT scan.
2 Tumor control rate includes stable disease, partial response and complete response.
3 Overall response rate measured by Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST 1.1). All responses included in ORR were partial responses (PRs).
4 Not evaluable due to no post baseline CT scan due to early withdrawal.

CCX872 was well tolerated by advanced pancreatic cancer patients. The incidence and rate of adverse events were consistent with data reported historically for FOLFIRINOX alone, suggesting no apparent additional safety burdens of combining CCX872 with FOLFIRINOX.

"Advanced pancreatic cancer is particularly challenging to treat, and represents a very high unmet medical need," said Pirow Bekker, M.D., Ph.D., Chief Medical Officer of ChemoCentryx. "While some earlier work with this mechanism looked at non-metastatic pancreatic cancer patients, we were keen on examining the effects of CCR2 inhibition in non-operable, metastatic disease in a multi-center setting. Given patients in our study may continue to receive treatment with CCX872 for as long as they are in a progression-free state, we will continue the study according to plan and evaluate progression-free survival later this year. Those data, as well as the potential longer term survival beyond that time, will help us in determining how best to proceed with CCR2 inhibition for pancreatic cancer."

About CCX872 Phase Ib Trial Design
The open-label, multi-center, ongoing Phase Ib clinical trial is designed to evaluate the safety and efficacy of orally administered CCX872 plus FOLFIRINOX in 50 patients with non-resectable pancreatic cancer. Patients receive 150 mg CCX872 twice daily for 12 weeks. After 12 weeks, patients who achieved stable disease or better (as measured by Response Evaluation Criteria In Solid Tumors, or RECIST 1.1), are eligible to continue on study for at least an additional 12 weeks unless disease progression occurs. Per protocol, the Eastern Cooperative Oncology Group (ECOG) performance status of patients in the trial is 0, 1 or 2. The primary efficacy measurement of the trial is progression-free survival (PFS) following at least 24 weeks of treatment.

About Pancreatic Cancer
It is estimated that over 337,000 cases of pancreatic cancer are diagnosed worldwide every year. In the United States, the annual incidence of pancreatic cancer is approximately 45,000; prevalence is only negligibly higher owing to the poor survival rates on current therapy. Within five years of diagnosis, 93 percent of patients die from their disease. Current standards of care include chemotherapeutic regimens that have significant toxicities and, in a minority of cases, surgical resection.

Amgen Obtains Global Development And Commercial Rights From Boehringer Ingelheim For Investigational BiTE® Immuno-Oncology Drug For Multiple Myeloma

On September 1, 2016 Amgen (NASDAQ:AMGN) and Boehringer Ingelheim reported that Amgen has acquired global development and commercial rights from Boehringer Ingelheim for BI 836909 (AMG 420), a bispecific T cell engager (BiTE) that targets B-cell maturation antigen (BCMA), a potential target for multiple myeloma (Press release, Amgen, SEP 1, 2016, View Source [SID:1234514867]). BI 836909 (AMG 420) is currently in Phase 1 studies. BI 836909 (AMG 420) was originally licensed to Boehringer Ingelheim by Micromet before the company was acquired by Amgen in 2012.

Under the provisions of the agreement, Amgen will work with Boehringer Ingelheim to assume responsibility for the clinical development of BI 836909 (AMG 420), transfer manufacturing, and lead global regulatory activity moving forward. Amgen will also receive worldwide commercialization rights for BI 836909 (AMG 420). Prior to this agreement, Boehringer Ingelheim held global development and commercialization rights. Financial terms of the agreement are not being disclosed.

"Obtaining global rights to BI 836909 (AMG 420) advances Amgen’s immuno-oncology strategy, allowing us to leverage our expertise with the BiTE platform to target BCMA in the multiple myeloma setting," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Multiple myeloma is a rare and aggressive blood cancer and despite new advances there is currently no cure.1-3 BI 836909 (AMG 420) allows us to explore a potential new treatment approach that harnesses the immune system to fight multiple myeloma."

"Boehringer Ingelheim is delighted that Amgen will continue our successful development of this important compound for multiple myeloma," said Dr. Jörg Barth, corporate senior vice president, Therapy Area Head Oncology at Boehringer Ingelheim. "Given Amgen’s focus in this disease area, we are convinced this best supports the future development for BI 836909 (AMG 420) and the goal to ultimately offer new treatment options for patients. Immuno-oncology and T cell engagers remain a key area of focus for Boehringer Ingelheim as well as providing innovative treatments for lung and blood cancers."

About BI 836909 (AMG 420)
BI 836909 (AMG 420) is a bispecific T cell engager (BiTE) that is under investigation for the treatment of multiple myeloma. BI 836909 (AMG 420) targets B-cell maturation antigen (BCMA), a target in multiple myeloma due to its restricted normal tissue expression and uniform expression on multiple myeloma cells. BI 836909 (AMG 420) is currently being evaluated in Phase 1 studies.

About BiTE Technology
Bispecific T cell engager (BiTE) antibody constructs are a type of immunotherapy being investigated for fighting cancer by helping the body’s immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibody constructs help place the T cells within reach of the targeted cell, with the intent of allowing T cells to inject toxins and trigger the cancer cell to die (apoptosis). BiTE antibody constructs are currently being investigated for their potential to treat a wide variety of cancers. For more information, visit www.biteantibodies.com.

Sunesis Pharmaceuticals Announces Poster Presentation on Preliminary Results from the Phase 1A Healthy Volunteer Study Evaluating Oral Non-Covalent BTK-inhibitor SNS-062 at the European School of Haematology’s 2nd International Conference on New Concepts in B-Cell Malignancies

On September 1, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that a poster detailing preliminary results from the Company’s Phase 1A study in healthy volunteers evaluating oral non-covalent BTK-inhibitor SNS-062 will be presented at the European School of Haematology’s 2nd International Conference on New Concepts in B-Cell Malignancies being held September 9-11, 2016, at the Estoril Congress Centre in Estoril, Portugal (Press release, Sunesis, SEP 1, 2016, View Source [SID:1234514866]).

The details for the poster presentation are as follows:

Date & Time: Saturday, September 10, 2016, from 6:50 p.m. to 8:20 p.m. Central European Time

Poster Title: A Phase 1a Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the Noncovalent Bruton Tyrosine Kinase (BTK) Inhibitor SNS-062 in Healthy Subjects: Preliminary Results

The poster will be available on the Sunesis website following the presentation.

OncoMed Pharmaceuticals Completes Enrollment of Phase 2 YOSEMITE Clinical Trial of Demcizumab in Pancreatic Cancer

On September 1, 2016 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical development-stage biopharmaceutical company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported the completion of patient enrollment of 207 patients in the randomized Phase 2 "YOSEMITE" clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of first-line metastatic pancreatic cancer (Press release, OncoMed, SEP 1, 2016, View Source [SID:1234514865]). Topline results are expected in the first half of 2017.

The YOSEMITE trial was designed to assess the efficacy and safety of demcizumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine (standard of care) compared to standard of care alone. The Phase 2 dose of demcizumab was 3.5 mg/kg every two weeks for up to 70 days. The primary endpoint of YOSEMITE is progression-free survival. Secondary and exploratory endpoints include overall survival, response rate, pharmacokinetics, immunogenicity, safety and biomarker analyses. Patients enrolled in the YOSEMITE Phase 2 were randomized into one of three study arms receiving 1) standard of care plus one course of demcizumab, 2) standard of care plus demcizumab followed by a second course of demcizumab after a 98-day wash-out period or 3) standard of care plus placebo. The YOSEMITE Phase 2 trial was conducted at 49 clinical sites in the U.S., Europe and Australia. OncoMed initiated YOSEMITE in April 2015.

"We would like to thank the patients and their caregivers as well as the investigators and study teams for their participation and support in this trial," said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. "Improving outcomes for patients with metastatic pancreatic cancer has proven to be highly challenging and the need for additional treatment options is of great importance. In Phase 1b studies, demcizumab combined with standard of care demonstrated promising response rates and survival trends, and we look forward to gaining further insights into demcizumab’s potential in pancreatic cancer from the Phase 2 YOSEMITE trial."

In OncoMed’s Phase 1b clinical trial of demcizumab truncated dosing and Abraxane plus gemcitabine, 14 of 28 (50%) patients evaluable for response achieved partial responses (unconfirmed) and another 11 (39%) achieved stable disease. Among 32 patients evaluable for survival in the Phase 1b, median progression-free survival was 7.1 months and median overall survival was 12.7 months for the patients who received one truncated 70-day course of demcizumab with Abraxane plus gemcitabine. The combination of demcizumab and Abraxane plus gemcitabine was generally well tolerated with fatigue, nausea and vomiting being the most common drug related toxicities. Final results from OncoMed’s Phase 1b trial of demcizumab were presented at the 2016 Gastrointestinal Cancers Symposium.

About Pancreatic Cancer
Pancreatic cancer is the third leading cause of cancer-related deaths. According to the American Cancer Society, each year in the United States there are approximately 49,000 new cases of pancreatic cancer and 41,000 deaths. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is less than one year.

About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway. Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

Demcizumab is currently being studied in two randomized Phase 2 clinical trials. The YOSEMITE trial is testing demcizumab with Abraxane plus gemcitabine versus Abraxane plus gemcitabine alone in first-line advanced pancreatic cancer patients. The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients. A Phase 1b trial combining demcizumab with the anti-PD1 antibody pembrolizumab in solid tumor patients was also initiated in early 2016. Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

Patients interested in learning more about participating in one of OncoMed’s ongoing clinical trials may learn more by calling 1-866-914-7347 or emailing [email protected]

Array BioPharma Announces FDA Acceptance of Binimetinib NDA for Patients with Advanced NRAS-Mutant Melanoma

On September 1, 2016 Array BioPharma (Nasdaq: ARRY) reported that the FDA has accepted its New Drug Application (NDA) for binimetinib with a target action date under the Prescription Drug User Fee Act (PDUFA) of June 30, 2017 (Press release, Array BioPharma, SEP 1, 2016, View Source [SID:1234514864]). Array completed its NDA submission of binimetinib in late June 2016 based on findings from the pivotal Phase 3 NEMO (NRAS MELANOMA AND MEK INHIBITOR) trial in patients with NRAS-mutant melanoma. The FDA also indicated that it plans to hold an advisory committee meeting (ODAC) as part of the review process. As previously reported, Array is currently preparing for an Application Orientation Meeting (AOM) with the FDA in September 2016, which it expects will include a discussion of the NDA package including clinical risk / benefit.

"There are very few treatment advances beyond immunotherapy for this devastating disease, which impacts one out of five advanced melanoma patients," said Victor Sandor, M.D., Chief Medical Officer, Array BioPharma. "Binimetinib is the first and only MEK inhibitor to demonstrate improvement on progression free survival in a Phase 3 trial for NRAS mutant melanoma patients."

About the Phase 3 NEMO Study

The NEMO trial, (NCT01763164), is an international, randomized Phase 3 study evaluating the safety and efficacy of 45 mg BID binimetinib, compared to 1,000 mg/m2 dacarbazine dosed every three weeks. Prior immunotherapy treatment was allowed, and patients underwent radiographic assessment of disease status every six weeks. Assessment of progression was determined by blinded central review. Over 100 sites across North America, Europe, South America, Asia and Australia participated in the study.

Results from the NEMO trial were presented at the 2016 ASCO (Free ASCO Whitepaper) Annual Meeting. The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. The median PFS on the binimetinib arm was 2.8 months, versus 1.5 months on the dacarbazine arm. In the pre-specified subset of patients who received prior treatment with immunotherapy, including ipilimumab, nivolumab or pembrolizumab, patients who received binimetinib experienced 5.5 months of median PFS, compared with 1.6 months for those receiving treatment with dacarbazine. While the results in the pre-specified sub-group of patients who had received prior treatment with immunotherapy are of interest, interpretation beyond overall consistency with the primary result should be made with care. Array anticipates that the primary consideration for marketing approval will be the results for the primary endpoint of the trial. In addition to improving PFS, binimetinib also demonstrated improvement in overall response rate (ORR) and disease control rate. While there was no statistically significant difference demonstrated in overall survival (OS), the median overall survival (mOS) favored the binimetinib arm. Under the NEMO protocol, and in accordance with accepted statistical practice, the subgroup analyses of OS are formally conducted only if the key secondary endpoint of OS reached statistical significance. Binimetinib was generally well-tolerated and the adverse events reported were consistent with previous results in NRAS-mutant melanoma patients.

Binimetinib is an investigational medicine and is not currently approved in any country.

About NRAS-Mutant Melanoma
Melanoma is the fifth most common cancer among men and the seventh most common cancer among women in the United States, with more than 76,000 new cases and nearly 10,000 deaths from the disease projected in 2016. Activating NRAS mutations are present in up to 20 percent of patients with metastatic melanoma, and is a poor prognostic indicator for these patients. Treatment options for this population remain limited beyond immunotherapy, and patients face poor clinical outcomes and high mortality.

About Binimetinib
MEK and BRAF are key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Research has shown this pathway regulates several key cellular activities including proliferation, differentiation, survival and angiogenesis. Inappropriate activation of proteins in this pathway has been shown to occur in many cancers, such as melanoma, colorectal and thyroid cancers. Binimetinib is a late-stage small molecule MEK inhibitor, which targets key enzymes in this pathway.

Binimetinib is currently being studied in several other oncology trials, including the Phase 3 COLUMBUS trial studying encorafenib in combination with binimetinib in patients with BRAF-mutant melanoma and the recently initiated BEACON trial that will study encorafenib in combination with binimetinib and cetuximab in patients with BRAF V600E-mutant colorectal cancer. Array projects COLUMBUS top-line results availability during the third quarter of 2016.