On June 5, 2017 Laminar Pharma, a pioneering clinical stage biopharmaceutical company developing a new generation of products modulating metabolism of membrane lipids based on the groundbreaking MLT platform, reported that the final results of the of MIN-001-1203 clinical study with 2OHOA in patients with advanced solid tumours, including malignant glioma, have been presented at a poster session within the Developmental Therapeutics and Translational Research track at the 2017 ASCO (Free ASCO Whitepaper) meeting in Chicago (Press release, Laminar Pharma, JUN 5, 2017, View Source [SID1234562097]). 5 leading clinical investigational sites in Spain and in the UK have participated in this study.

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2OHOA, administered as an oral suspension two (BID) or three (TID) times daily, has been generally well tolerated in monotherapy up to 12 g/day, while patients have had difficulties to handle the large volume of liquid intake required for 16g/day (8 g BID), experiencing frequent gastrointestinal effects. Overall 54 patients have received 2OHOA at different doses. One Dose Limiting Toxicity (DLT) was reported at the dose of 12g/day and 3 DLT at 16g/day. 12G/day (4g TID) was confirmed as the maximum Tolerated Dose (MTD) since there were no DLTs reported in the second part of the study conducted with this dose (expansion phase)

No drug-related serious adverse events or other relevant toxicity effects associated to the investigational product have been reported in any of the 54 patients treated, other than the tolerability issues experienced at the highest dose levels (gastrointestinal effects). Study drug related AE (≥10%) at any grade were diarrhoea (53 [26%]), vomiting (29[14%]), nausea (26 [13%]). No G3/G4 whether regardless of study drug relationship or suspected as being study drug related occurred over 10% of patients.

Pharmacokinetic (PK) profile was determined. 2OHOA was quantifiable in all dose levels and maximum concentration (Cmax) was reached at 1 hour after administration in the fasted state. When administered under fed conditions, 2OHOA had bioavailability comparable to that found in the fasted state, although food caused a non-clinically significant delay in the time needed to reach the CMax. Therefore, 2OHOA could be taken without regard to food. The half-life was between 1.4 and 4.6 hours up to 8g/day, increasing to more than 7h at the higher doses. Systemic exposure of 2OHOA increased in proportion to dose following single and repeat BID administration. After repeat BID dosing, systemic exposure of 2OHOA, increased between 1- and 1.7-fold from first dose on Day 1 to last dose on Day 21. PK data supports the planned twice-a-day oral administration of 2OHOA

Very encouraging anti-cancer activity of 2OHOA as single agent has been confirmed in several recurrent, heavily pre-treated patients, including 5 recurrent High Grade Glioma (rHGG) and 3 with other advanced solid tumours (AST). One recurrent glioblastoma (rGBM) pt had sustained partial response for more than 2.5 years (93% shrinkage of target lesion) and 4 rHGG patients (3 GBM) achieved stable disease (SD), by RANO, for at least 6 months. Other 3 AST patients had clinical benefit by RECIST: 1 with mesothelioma (SD for 10 months), 1 with colorectal cancer (SD for 3 months) and 1 with lung metastasis of biliary duct carcinoma (SD for 5 months)

Preliminary analysis of available biomarkers data confirms biological activity by 2OHOA in cancer patients. On the one hand, a reduction of GFAP levels in plasma from rHGG patients after 8 days of treatment was observed in more than 80% of patients analyzed. Average reduction in GFAP levels in the whole set of patients was 20% (n=15). On the other hand, initial analysis of plasma miRNA expression profiles in a subset of 22 patients, shows that at least 3 miRNA were differentially expressed in response to 2OHOA treatment. Target gene analysis of these miRNA is ongoing. These, and other potential plasmatic biomarkers currently being analyzed, are expected to be developed and eventually validated in future clinical studies with 2OHOA, providing valuable support for patient selection strategies and for clinical study design.

Further clinical studies with 2OHOA are currently under preparation, including a Phase IIb study to evaluate the potential clinical benefit of adding 2OHOA to the current Standard of Care (SoC) in patients with newly-diagnosed glioblastoma, given that "the preliminary antitumor activity including a sustained PR in heavy pretreated rHGG pt warrants further investigation in a Ph2 study", as concluded in the poster presented by Dr. A. Azaro, Principal investigator at Vall d’Hebron Institute of Oncology (VHIO), one of the 5 sites participating in this study, and the first author of the poster presented at ASCO (Free ASCO Whitepaper).

Laminar Pharma is also preparing a PI trial in children with malignant glioma and other advanced cancers is being prepared in the USA, with the collaboration of top clinical investigational institutions in New Jersey and Boston.

On June 5, 2017 Cornerstone Pharmaceuticals, Inc., a clinical-stage, oncology-focused pharmaceutical company, reported that it is changing its corporate name to Rafael Pharmaceuticals, Inc., effective immediately (Press release, Rafael Pharmaceuticals, JUN 5, 2017, View Source [SID1234521069]). The name change signifies a new era in the company’s evolution during which the company aims to usher in a new paradigm in anticancer treatment with its breakthrough metabolic cancer drugs. The new name is derived from Raphael, the biblical angel of healing.

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"Over the past few months we’ve gained a lot of momentum across several facets and this is an ideal moment to effectuate our name change," said Howard Jonas, Executive Chairman of Rafael Pharmaceuticals. "We’ve strengthened our company’s foundation by making key hires, by adding renowned scientists and clinicians to our advisory boards, and by adding leaders in the pharmaceutical and scientific research communities to our Board of Directors. Moreover, we’ve made substantial progress towards commercializing our proprietary Altered Energy Metabolism Directed (AEMD) drug platform. Most notably, we recently completed successful End-of-Phase I Type B Meetings with the FDA, and now have approval from the FDA to initiate pivotal trials for CPI-613 in acute myeloid leukemia (AML) and pancreatic cancer."

On June 5, 2017 Novartis reported it has entered into a clinical research collaboration in which Bristol-Myers Squibb will investigate the safety, tolerability, and efficacy of Mekinist (trametinib) in combination with Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a potential treatment option for metastatic colorectal cancer in patients with microsatellite stable tumors where the tumors are proficient in mismatch repair (MSS mCRC pMMR) (Press release, Novartis, JUN 5, 2017, View Source [SID1234519452]).

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Under the terms of the agreement, the study will be conducted by Bristol Myers-Squibb and is expected to establish recommended dose regimens and the preliminary anti-tumor activity of the combination therapies. Both Bristol Myers-Squibb and Novartis will evaluate the results to determine optimal approaches and potential clinical development of these combinations.

"Novartis has a longstanding heritage in exploring the combination of medicines to broaden our knowledge of mutational driven cancers and develop innovative treatments," said Vas Narasimhan, MD, Head, Global Drug Development and Chief Medical Officer, Novartis. "Along with our ongoing internal immuno-oncology efforts, the expansion of our collaboration with Bristol-Myers Squibb further advances our collective goals to advance the science and to support patients in need."

About Colorectal Cancer
Worldwide, colorectal cancer is the third most common type of cancer in men and the second most common in women, with approximately 1.4 million new diagnoses in 2012. Of these, nearly 750,000 were diagnosed in men, and 614,000 in women[1]. Globally in 2012, approximately 694,000 deaths were attributed to colorectal cancer[1]. In the U.S. alone, an estimated 135,430 patients will be diagnosed with cancer of the colon or rectum in 2017, and approximately 50,000 are estimated to die of their disease[2]. There is wide variation in 5-year survival rates across disease stages, with 5-year survival rates for patients with metastatic or stage IV colorectal cancer around 11%[3]. The incidence of microsatellite stability (MSS) in colorectal tumors varies by stage, with 80% to 85% of exhibiting MSS[4].

About Mekinist and Important Safety Information
MEKINIST is a kinase inhibitor indicated, as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. MEKINIST is not indicated for treatment of patients who have received prior BRAF-inhibitor therapy. MEKINIST can cause serious side effects including new primary malignancies (cutaneous and non-cutaneous), hemorrhage, inflammation of the colon and perforation of the intestines, blood clots in the legs, cardiomyopathy, eye toxicity, interstitial lung disease, serious fevers, serious skin toxicity, hyperglycemia, and harm to a fetus. Some of these side effects can be fatal in rare cases. The most common side effects when MEKINIST is used as a single-agent are rash, diarrhea, and lymphedema.

About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, Bristol-Myers Squibb’s Opdivo and Yervoy (link is external) combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

About Yervoy
Yervoy, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of Yervoy effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is now approved in more than 40 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. This includes Phase 3 trials in prostate and lung cancers.

On June 5, 2017 Polaris Group reported that its lead therapeutic ADI‑PEG 20 (pegylated arginine deiminase) in combination with pemetrexed and cisplatin (ADIPemCis) is active in argininosuccinate synthetase (ASS1) deficient malignant pleural mesothelioma (MPM), including non-epithelioid MPM, which carries an unfavorable prognosis and historically responds poorly to chemotherapy (Press release, Polaris Pharmaceuticals, JUN 5, 2017, View Source [SID1234526285]). The results were generated from a phase 1b dose escalation and expansion study (TRAP), led by Dr. Peter Szlosarek of Barts Cancer Center, Queen Mary University of London, and presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s 2017 annual meeting.

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Thirty one (31) MPM patients (11 epithelioid and 20 non-epithelioid) were enrolled and treated with fixed-dose pemetrexed and cisplatin (PemCis), the standard first-line chemotherapy for MPM, in combination with increasing doses of ADI‑PEG 20. The treatment appeared to be safe and well tolerated. The partial response rate was 35.5% (95% CI 19.2%-54.6%) with a disease control rate of 93.5% (95% CI 78.6%-99.2%). Median progression free survival was 5.6 months (95% CI 4-6) and median overall survival was 10.1 months (95% CI 6.7-17.7).

"Based on the encouraging efficacy signal from the TRAP study, we have initiated a randomized, double blind, phase 2/3 trial comparing ADI‑PEG 20+PemCis with PemCis in patients with non-epithelioid MPM," said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc. "With ADI‑PEG 20+PemCis, we hope to bring an effective treatment to this subset of MPM patients, who have a dire need for medical intervention."

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.