On January 16, 2015 Peregrine Pharmaceuticals reported on the presentation of clinical data related to the company’s immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (Press release Peregrine Pharmaceuticals, JAN 16, 2015, View Source [SID:1234501385]). This conference is being held January 15-17, 2015 at the Moscone West Convention Center in San Francisco, California.

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The clinical presentation titled: "A Phase II Study of Bavituximab and Sorafenib in Advanced Hepatocellular Carcinoma (HCC)" will be presented this afternoon by Adam Yopp, M.D., assistant professor of surgery at the University of Texas Southwestern Medical Center Dallas, Texas.

In this single-center, single-arm, open-label investigator-sponsored trial (IST), 38 patients with advanced HCC received bavituximab (3mg/kg) weekly and sorafenib (400 mg) twice daily until disease progression or toxicity. Data show that the combination of bavituximab and sorafenib is associated with an improved time to progression (TTP) of 6.7 months, a disease specific survival (DSS) of 8.7 months, a disease control rate (DCR) of 58% (22 out of 38 patients) and a 4-month progression-free survival (PFS) of 62%. Two patients (5%) achieved a partial response according to Response Evaluation Criteria In Solid Tumors (RECIST). The secondary endpoint of median overall survival (OS) was 6.2 months. The combination of bavituximab and sorafenib was well-tolerated in patients with advanced HCC with no indications of autoimmune adverse events that have been seen with other checkpoint immunotherapies.

"These clinical outcomes of time to progression, disease control rate and 4-month progression-free survival are quite encouraging, especially in this heavily pretreated patient cohort with very poor prognosis due to their unfavorable disease biology including a high rate of macrovascular invasion," said Dr. Yopp. "I was also pleased to see an extended tail in the survival curve that is typical of emerging immunotherapies for cancer. The positive data from this study should be considered as rationale for future randomized trials to further evaluate the potential of bavituximab in liver cancer."

"These data, along with recently reported translational data from this study, continue to build the knowledge base for the bavituximab clinical program and, in particular, highlight the potential immunotherapeutic synergies of bavituximab and sorafenib. We agree with Dr. Yopp that these data warrant further clinical evaluation of this combination in later stage clinical trials," said Joseph Shan, vice president of clinical and regulatory for Peregrine. "We continue to build value in the bavituximab program across multiple programs including the execution of the SUNRISE Phase III trial in second-line, non-small cell lung cancer and from data generated from this and other investigator-sponsored trials as well as other ongoing clinical trials. We look forward to new clinical collaborations with the goal of further exploring the utility of bavituximab in combination with other immuno-oncology drugs."

Liver IST Clinical Translation Data

Recently presented translational data of six patients from this trial show that half of the patients evaluated had an increase in tumor fighting immune cells following one cycle of bavituximab treatment, similar to what has been shown for PS-targeting antibodies in multiple preclinical cancer models. In addition, the increase in immune response was associated with patients that remained on study treatment for longer time periods, suggesting the possibility of a clinically meaningful anti-tumor immune response. Three of the six patients evaluated had increased infiltration of activated tumor-fighting T-cells (CD8) into the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these responding patients initially expressed lower levels of PD-1 positive cells, an established marker of T-cell activation and disease outcome, prior to the initiation of therapy that was followed by a measurable rise post bavituximab treatment.

On January 16, 2015 OncoMed Pharmaceuticals reported final safety, efficacy and biomarker data from the company’s Phase 1b "ALPINE" clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in 40 patients with frontline metastatic pancreatic cancer (Press release OncoMed, JAN 16, 2015, View Source [SID:1234501384]).

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Tarextumab was generally well tolerated when administered with gemcitabine and Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound), with manageable, on-target drug-related toxicities. The Phase 2 dose of tarextumab was determined to be 15 mg/kg every two weeks in combination with the standard-of-care. Among patients evaluable for response using RECIST criteria, 38 percent (11 of 29) achieved partial responses, with an additional 35 percent achieving stable disease (10 of 29) for an overall clinical benefit rate of 73 percent (21 of 29 patients). Median progression-free survival and overall survival values for the three drug combination of tarextumab-gemcitabine-Abraxane were 5.6 months and 11.6 months, respectively, for all patients treated with the three-drug combination.

The data presented included biomarker analyses that showed that among patients whose tumor samples had elevated levels of Notch3 gene expression, trends toward higher response rates and longer survival were noted, as compared to patients with low Notch3 expression. Median PFS and OS for patients with high Notch 3 expression (using a 50% cut-off) were 6.6 months and 14.6 months, respectively. Given the small sample size and potential imbalances in patient characteristics, these encouraging preliminary efficacy and predictive biomarker observations are being assessed in the ongoing randomized, placebo-controlled, Phase 2 ALPINE trial

"The positive data from the Phase 1b study of tarextumab in first line pancreatic cancer patients provide us with clear support for the advancement of this drug into Phase 2," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "The randomized Phase 2 ALPINE study, which began enrolling patients in July of 2014, is enrolling rapidly and we believe the ALPINE study will be the first of our randomized Phase 2 trials to read out, with data expected in the first half 2016."

"Tumor Notch3 gene expression is estimated to be elevated in approximately 70 percent of pancreatic cancer patients and it is thought to be an indicator of poor prognosis and chemotherapy resistance. The data suggesting that the biomarker-positive patients may have improved response rates and survival with tarextumab treatment are supportive of the Phase 2 design of the ALPINE study where tarextumab’s impact on efficacy of all patients enrolled as well as the biomarker positive patients will be assessed. The Notch3 predictive biomarker may enable us to identify those patients that would gain the greatest benefit from tarextumab treatment," added Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.

"Pancreatic cancer remains among the most challenging cancers in spite of recent treatment advances. The Phase 1b tarextumab data confirm safety and early signals of efficacy observed in earlier stage studies," said Eileen O’Reilly, M.D., Associate Director, Clinical Research with Memorial Sloan Kettering Cancer Center and a Principal Investigator of ALPINE. "Further exploration of tarextumab’s potential as a new treatment option for pancreatic cancer patients is warranted and ongoing in the randomized Phase 2 portion of the study. The trial will evaluate the addition of tarextumab in a frontline untreated pancreas cancer population and in specific biomarker-selected subsets."

In the Phase 1b study, tarextumab was administered to standard-of-care chemotherapy to 40 patients with previously untreated, metastatic pancreatic cancer. Thirty-one of the patients received the combination of gemcitabine, Abraxane and tarextumab. Escalating doses of tarextumab were administered every two weeks, ranging from 2.5 mg/kg to 15 mg/kg. Diarrhea, fatigue and anemia were the most common treatment-related toxicities, and the events were mostly Grade 1 or 2, and managed with supportive care. The randomized, double blinded Phase 2 portion of the ALPINE study is currently enrolling patients with first-line advanced pancreatic cancer at 36 clinical sites in the United States. Data are anticipated in the first half of 2016 for both the intent to treat population as well as the tumor Notch3 biomarker positive patients.

On January 12, 2015 Tokai Pharmaceuticals reported that it has entered into an agreement with the Johns Hopkins University related to the development of a companion diagnostic to determine the AR-V7 status of patients with castration-resistant prostate cancer (CRPC) for use with the Company’s lead product, galeterone, which is in development for the treatment of AR-V7 positive metastatic CRPC (Filing 8-K , Tokai Pharmaceuticals, JAN 15, 2015, View Source [SID:1234501348]).

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Under the agreement, the Company has obtained an exclusive, worldwide license from the Johns Hopkins University to patent applications and know-how covering an assay that has been used to determine the AR-V7 status of prostate cancer patients.

AR-V7 positive prostate tumors express a truncated form of the androgen receptor (AR). These truncated ARs are missing the C-terminal end of the receptor that contains the ligand binding domain, which is known as C-terminal loss. The AR splice variant AR-V7 is the most prevalent of the splice variants that cause C-terminal loss.

Clinical data from a prospective trial at the Johns Hopkins University as well as retrospective analyses of studies at MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center have shown that AR-V7 specifically and C-terminal loss generally is associated with poor responsiveness to Zytiga (abiraterone acetate) and Xtandi (enzalutamide), two commonly used oral therapies for metastatic CRPC. The Company believes that galeterone has the potential to treat patients with AR-V7 based on data from preclinical studies and retrospective data in patients with C-terminal loss from the Company’s Phase 2 ARMOR2 trial of galeterone.

"We are pleased to have formalized the agreement with the Johns Hopkins University to support our ongoing AR-V7 companion diagnostic program. This license adds to the intellectual property around galeterone and is a critical milestone in the development of the companion diagnostic that will be used in our 148 patient Phase 3 ARMOR3-SV trial scheduled to begin in the first half of this year," stated Jodie Morrison, president and chief executive officer of Tokai Pharmaceuticals. "It is our hope that future availability of a companion diagnostic will allow prostate cancer patients and their physicians to make more informed decisions regarding their care."

In addition, the Company announced that it has entered into an agreement with Qiagen N.V. under which Qiagen will develop a non-invasive companion diagnostic utilizing an array of novel technologies for use with galeterone. The agreement formalizes an existing collaboration under which work has been ongoing.

On January 15, 2015 Amgen reported on new data from the Phase 2 PEAK and Phase 3 PRIME studies that support the first-line use of Vectibix (panitumumab) in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, in patients with wild-type RAS (absence of exons 2, 3, or 4 KRAS or NRAS mutations) metastatic colorectal cancer (mCRC) (Press release Amgen, JAN 15, 2015, View Source;p=RssLanding&cat=news&id=2008116 [SID:1234501347]). The data will be presented during a poster session at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place in San Francisco from January 15 to 17.

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In an exploratory analysis from the PEAK study (abstract #660), treatment with Vectibix compared to bevacizumab (Avastin) resulted in a significantly higher proportion of patients with earlier tumor shrinkage at week eight (64 percent vs. 45 percent, respectively; 95 percent CI, p=0.0232), and among responding patients, a significantly longer duration of response (11.4 vs. 8.5 months, respectively; 95 percent CI, p=0.0142) and greater depth of response (65 percent vs. 46 percent, respectively; p=0.0007). Overall response rates (ORR) appeared to be similar between Vectibix and bevacizumab. This is consistent with observed overall survival (OS) and progression-free survival (PFS) rates, and with data previously reported. The safety profile of Vectibix was consistent with previously reported studies.

"These analyses help deepen our understanding of how Vectibix works when added to a standard first-line chemotherapy for the treatment of wild-type RAS metastatic colorectal cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Our Vectibix clinical trial program continues to yield new insights regarding biomarkers and drug sequencing."

While the primary analysis from PEAK showed similar ORR between the Vectibix- and bevacizumab-based regimens, this exploratory analysis demonstrates that Vectibix produces early, sustained anti-tumor activity, which may in part explain the OS and PFS benefits seen with Vectibix versus bevacizumab in this trial.

A separate analysis from the Phase 3 PRIME study (abstract #537), demonstrated that there were no significant differences in quality of life among patients treated with Vectibix plus FOLFOX versus FOLFOX alone despite the incidence of adverse events associated with each treatment regimen. The quality of life analysis included a scale that assessed mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Colorectal cancer is the third most common cancer found in both men and women in the U.S. and is the second leading cause of cancer deaths. Approximately 1.2 million cases of colorectal cancer are expected to occur globally each year.