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Celator(R) Pharmaceuticals Announces Phase 3 Clinical Study of CPX-351 Achieved Target Enrollment in High Risk (Secondary) Acute Myeloid Leukemia

On October 27, 2014 Celator Pharmaceuticals reported that the target enrollment of 300 patients has been achieved in the company’s multicenter, randomized, open-label Phase 3 study of CPX-351 (cytarabine:daunorubicin) Liposome for Injection versus the current standard of care, conventional cytarabine and daunorubicin therapy (7+3) in patients with untreated high-risk (secondary) acute myeloid leukemia (AML) (Press release Celator Pharmaceuticals, OCT 27, 2014, View Source [SID:1234500882]). The study randomized the 300th patient ahead of schedule and will remain open for a short time to enable all patients currently in the process of referral and evaluation to complete enrollment into the study.

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"AML continues to be a devastating condition with a particularly poor prognosis in the high-risk population. Unlike other cancers, treatments for AML have not significantly advanced patient outcomes for several decades. Based on results to date and the combination-optimizing mechanism behind CPX-351, I am hopeful that we can soon offer a superior option to standard chemotherapy in older patients with high-risk AML," commented Jeffrey Lancet, M.D., Senior Member and Chief of the Leukemia/Myelodysplasia Program at Moffitt Cancer Center.

Celator is conducting the pivotal Phase 3 study in partnership with The Leukemia & Lymphoma Society (LLS). The study enrolled patients between the ages of 60 and 75 with newly diagnosed, previously untreated AML arising from prior myelodysplasia or chronic myelomonocytic leukemia, prior history of chemotherapy or radiotherapy treatment, or with cytogenetic evidence of abnormalities associated with myelodysplasia. Patients were randomized to receive CPX-351 (100u/m2; Days 1, 3, 5) or conventional 7+3 chemotherapy. The primary efficacy endpoint of the study is overall survival. Secondary endpoints include complete response (CR+CRi) rate, duration of remission, 30- and 60-day mortality, event-free survival, aplasia rate, and rate of stem cell transplant. The study began enrollment in December 2012 and is being conducted at leading institutions in the U.S. and Canada. Results from the final analysis of induction response rate are expected in the second quarter of 2015, and overall survival data, the primary endpoint of the study, are expected in the first quarter of 2016.

"We are excited to achieve our target enrollment ahead of schedule and believe it demonstrates both the great need for a new treatment for AML patients, as well as strong clinical interest in CPX-351," said Scott Jackson, Chief Executive Officer of Celator Pharmaceuticals. "Completion of patient accrual in this pivotal Phase 3 study is an important milestone for Celator. We look forward to reporting the induction response rate results in the second quarter of 2015 and we project the primary endpoint data of overall survival to be available in the first quarter of 2016. In addition, we are especially grateful to the patients, the clinical investigators, and our partner, the LLS, for participating in this study."

CTI Acquires Exclusive Worldwide License to Tosedostat, a Selective Oral Anti-Cancer Therapy

On October 27, 2014 CTI BioPharma reported that it has acquired worldwide rights to tosedostat through concurrent transactions with Vernalis R&D Limited (Vernalis), the originator of tosedostat, and Chroma Therapeutics Ltd. (Chroma), through which CTI previously held a sublicense with respect to tosedostat in North, Central and South America (Press release CTI BioPharma, OCT 27, 2014, View Source;p=RssLanding&cat=news&id=1981514 [SID:1234500881]). Tosedostat is a first-in-class selective inhibitor of aminopeptidases, which are required by tumor cells to provide amino acids necessary for growth and tumor cell survival. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS), which are intended to inform the design for a Phase 3 registration study to support potential regulatory approval.

"Our portfolio strategy is to acquire novel best-in-class agents that, either as monotherapy or in combination with other therapies, can have a profound effect in the treatment of patients with blood-related cancers," said James A. Bianco, M.D., President and CEO of CTI. "We are committed to building our blood-related cancer franchise. We feel there is strong interest in this oral, once-daily drug candidate, which we believe is attributable to the positive clinical results to date, and we are pleased to have exclusive worldwide rights to develop tosedostat for patients in areas where there remains an unmet medical need. Over the next year, CTI and its advisors intend to develop a registration path for tosedostat in the US and Europe. In the event of positive clinical data and productive regulatory discussions, we would intend to start a pivotal program commencing in 2016."

Under the terms of an asset purchase agreement with Chroma, CTI acquired all of Chroma’s right, title and interest in tosedostat and certain related assets in exchange for issuing to Chroma $21.3 million in shares of CTI’s preferred stock convertible into 9 million shares of CTI common stock, 12 percent of which has been placed in escrow pending expiry of Chroma’s indemnification obligations. Chroma and CTI also terminated their prior license agreement relating to tosedostat, thereby eliminating potential future developmental and sales milestone payments by CTI of up $209 million thereunder. Concurrently, CTI entered into a license agreement with Vernalis for the exclusive worldwide right to use certain patents and other intellectual property rights to develop, market and commercialize tosedostat and certain other analogues. Under the Vernalis license agreement, CTI agreed to make tiered royalty payments of no more than a high single-digit percentage, on a country-by-country basis, for the longer of ten years following commercial launch or the expiration of relevant patents.

Cancer Research UK and Leukaemia & Lymphoma Research team up to boost blood cancer trials

On October 27, 2014 Cancer Research UK, with its commercial arm Cancer Research Technology, and Leukaemia & Lymphoma Research reported that they have signed a deal to jointly fund early phase clinical trials of experimental drugs for patients with blood cancers (Press release, Cancer Research Technology, OCT 27, 2014, View Source [SID1234523220]).

This collaboration will increase support for trials of promising new treatments for blood cancers – leukaemias, lymphomas and myeloma – which affect around 30,000 people every year in the UK.

Leukaemia & Lymphoma Research will provide access to promising new treatments that are being researched by its scientists, as well as financial support for Cancer Research UK to develop these therapies through preclinical, and early Phase I and Phase II clinical development.

The trials will be managed and run by Cancer Research UK’s Centre for Drug Development through the Experimental Cancer Medicine Centre (ECMC) network, an initiative funded by Cancer Research UK and the UK’s four Health Departments, at hospitals across the country.

Cancer Research Technology will be responsible for the further clinical and commercial development of joint projects, ensuring that both charities receive a proportion of revenues from any drugs that ultimately reach the market. The agreement will initially last five years, with up to five trials anticipated to be funded in that time.

Professor Chris Bunce, research director at Leukaemia & Lymphoma Research, said: "We are at an exciting period in blood cancer research, with our scientists identifying more treatment targets and developing more drugs than ever before. The infrastructure and know-how exchanged by working together with Cancer Research UK will enable this initiative to give patients access to potentially life-saving breakthroughs sooner.

"There is an urgent need for new blood cancer drugs, as many patients cannot tolerate or do not respond to traditional treatment options like chemotherapy."

Dr Nigel Blackburn, director of Cancer Research UK’s Centre for Drug Development, said: "Bringing together Cancer Research UK’s cutting-edge facilities and expertise, with Leukaemia & Lymphoma Research’s high quality research is an exciting prospect that we hope will bring promising new treatments to patients with blood cancer sooner.

"As the world’s largest charity dedicated to cancer research, we hope this will pave the way for further strategic partnerships with other charities who are interested in working together to speed up the translation of today’s scientific discoveries into future cancer treatments."

Merck Receives FDA Breakthrough Therapy Designation for KEYTRUDA® (pembrolizumab) in Advanced Non-Small Cell Lung Cancer

On October 27, 2014 Merck reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy, for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy (Press release Merck & Co, OCT 27, 2014, View Source [SID:1234500883]). This is the second Breakthrough Therapy Designation granted for KEYTRUDA.

“The FDA’s Breakthrough Therapy Designation of KEYTRUDA underscores that new treatment approaches for advanced non-small cell lung cancer continue to be needed,” said Dr. Roger Perlmutter, president, Merck Research Laboratories. “Our data investigating the use of KEYTRUDA in this difficult-to-treat malignancy are very encouraging, and we look forward to working closely with the FDA to expedite our clinical program.”

KEYTRUDA is indicated in the United States at a dose of 2 mg/kg every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The Breakthrough Therapy Designation in advanced NSCLC is supported by data from the ongoing Phase 1b KEYNOTE-001 study, and updated findings were recently presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2014 Congress. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. KEYTRUDA was previously granted breakthrough status for advanced melanoma.

KEYTRUDA is being studied across more than 30 types of cancers, as monotherapy and in combination. In advanced lung cancer, Merck is advancing a clinical program investigating the use of KEYTRUDA as monotherapy and in combination across lines of therapy and histology, including exploring different tumor characteristics such as PD-L1 expression as predictors of responsiveness. There are two ongoing Phase 2 and 3 studies in advanced lung cancer (KEYNOTE-010 and KEYNOTE-024) and an additional Phase 3 study is planned to begin in the fourth quarter of 2014 (KEYNOTE-042).

XTANDI (ENZALUTAMIDE) CAPSULES RECEIVE POSITIVE CHMP OPINION FOR THE TREATMENT OF MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO ARE CHEMOTHERAPY-NAÏVE

On October 24, 2014 Astellas Pharma Europe reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending a variation to amend the Marketing Authorisation for enzalutamide (trade name XTANDI) (Press release Astellas, OCT 26, 2014, View Source [SID:1234500880]). The positive opinion relates to the use of enzalutamide for the treatment of adult men with metastatic castrate-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen-deprivation therapy in whom chemotherapy is not yet clinically indicated.

"For us urologists treating patients with mCRPC, this positive opinion from the CHMP is an important milestone towards making enzalutamide available across Europe. Enzalutamide marks a significant step for many patients who live with mCRPC as encouraging, it demonstrates benefits in overall survival, has a positive impact on quality of life and has been shown to be well tolerated", said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology and Professor of Physiology, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. "As well as clear efficacy and safety benefits over placebo, enzalutamide has the additional advantage of not requiring steroids to be taken concomitantly and requires only basic monitoring, making it a simple option for both healthcare professionals and patients. It is my hope that the European Commission follows this opinion, providing us with a viable new treatment option for those patients not suitable for chemotherapy.

The positive CHMP opinion is based on results from the phase III PREVAIL study which showed that men treated with enzalutamide demonstrated a statistically significant reduction both in the risk of death and a delay in cancer progression and the time to initiation of chemotherapy as compared to those treated with placebo.

Enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.001), compared with placebo. In addition, treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19; p<0.001). Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001).

The most common clinically relevant adverse events among the enzalutamide population as compared with placebo-treated patients in the PREVAIL trial included fatigue, hot flush and hypertension. Hypertension was observed in 13% of enzalutamide versus 4% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 3% of enzalutamide versus 2% of placebo-treated patients. One patient (0.1%) out of the 871 patients treated with enzalutamide, and one patient (0.1%) receiving placebo experienced a seizure.

In the EU, the European Commission generally follows the recommendations of the CHMP opinion and delivers its final decision around two months after the CHMP recommendation.

XTANDI is currently licensed in Europe for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel therapy. Marketing authorisation was granted by the European Commission in June 2013.