On July 31, 2014 ZIOPHARM Oncology, Inc. (“ZIOPHARM”) (Nasdaq: ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, and Solasia Pharma K.K. (“Solasia”), a developer of oncology pharmaceuticals in-licensed for commercialization in major markets throughout the world, reported an amendment and restatement of their License and Collaboration Agreement for darinaparsin (Zinapar or ZIO-101) and related organoarsenic molecules (Press release, Solasia, JUL 31, 2014, View Source [SID1234520951]).

Under the terms of the amended and restated agreement, ZIOPHARM granted Solasia an exclusive worldwide license to develop and commercialize darinaparsin, and related organoarsenic molecules, in both intravenous and oral forms in all indications for human use. In exchange, ZIOPHARM will be eligible to receive from Solasia up to $72.2 million in development-and sales-based milestones, a royalty on net sales of darinaparsin, once commercialized, and a percentage of any sublicense revenues generated by Solasia. Solasia will be responsible for all costs related to the development, manufacturing and commercialization of darinaparsin. The new agreement amends and restates a 2011 agreement between the parties under which Solasia was granted exclusive rights by ZIOPHARM to darinaparsin in the territories of Japan, China, Hong Kong, Macau, Republic of Korea, Taiwan, Singapore, Australia, New Zealand, Malaysia, Indonesia, Philippines and Thailand.

Darinaparsin is a novel mitochondrial-targeted agent (organoarsenic) being developed for the treatment of various hematologic and solid cancers. It has been granted Orphan Drug Designation in the U.S. and Europe as a treatment of peripheral T-cell lymphoma (PTCL).

“As our strategic focus has shifted exclusively toward DNA therapeutics and immuno-oncology, Solasia, with whom ZIOPHARM has had a longstanding partnership, is the natural choice to advance the development of darinaparsin on a global basis,” said Jonathan Lewis, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. “Through a collaboration that began in 2011, Solasia has built a meaningful scientific and clinical understanding of darinaparsin, providing a strong foundation for realizing its long-term clinical value. Further, by expanding this agreement to all global territories, there exists now an additional strong incentive for Solasia to rapidly and strategically develop this potentially important product candidate in areas of unmet medical need in oncology.”

“Solasia stands to benefit greatly from the acquisition of exclusive global development and commercialization rights to darinaparsin from ZIOPHARM,” said Yoshihiro Arai, President and Representative Director of Solasia Pharma K.K. “Our initial Asian clinical studies with darinaparsin in the clinical setting of PTCL have been very exciting and encouraged us to expand our longstanding partnership with ZIOPHARM in order to maximize our opportunity with
the darinaparsin program throughout the world. We presently plan to start pivotal clinical trials in Asia early in 2015.”

On July 30, 2014 Bayer reported that the oncology compound Stivarga (regorafenib) has been approved by the European Commission (EC) for the treatment of adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST) who progressed on or are intolerant to prior treatment with imatinib and sunitinib (Press release Bayer, JUL 30, 2014, View Source [SID:1234500668]). The approval of Stivarga in GIST is based on results from the pivotal Phase III study (GRID) that demonstrated a statistically significant improvement in progression-free survival (PFS) compared to placebo in patients with GIST whose disease had progressed after prior treatments. Stivarga is already approved in the EU for the treatment of patients with metastatic colorectal cancer (mCRC).

“Following the approval of Stivarga for GIST in several countries worldwide, including the U.S. and Japan, we are delighted to offer patients in Europe a new option for treating this rare yet relentless cancer,” said Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development. “At Bayer, we are dedicated to exploring solutions for different tumor types and drive innovation to meet the unmet needs of both physicians and patients.”

“GIST is a highly aggressive cancer that can go undetected for years and, at the point of diagnosis, most patients have already progressed to advanced stages of disease. Survival rates are low and treatments are limited after imatinib and sunitinib,” said Jean Yves-Blay, GRID investigator, Professor of Medicine in Medical Oncology and Head of the Medical Oncology Department, Centre Leon Berard at Université Claude Bernard in Lyon, France. “The Phase III GRID trial demonstrated that progression-free survival with regorafenib is more than five times than with placebo, a significant improvement for those who have progressive disease.”

“One of the hardest things to hear from your doctor is that there is no treatment left for your disease,” said Markus Wartenberg, Member of the Board of Directors of the Sarcoma Patients EuroNet Association (SPAEN). “In rare cancers such as GIST, hope empowers people to continue fighting the cancer. New treatment options are welcomed so that patients can continue to defy their illness.”

The results of the pivotal Phase III GRID study showed that regorafenib plus best supportive care (BSC) significantly improved progression-free survival (PFS) compared to placebo plus BSC (HR=0.268 [95% CI 0.185-0.388], p<0.0001) in patients with metastatic and/or unresectable GIST who were previously treated with imatinib and sunitinib, reducing the risk of progression or death by 73%. The median PFS was 4.8 months in the regorafenib arm versus 0.9 months in the placebo arm (p<0.0001). The increase in PFS was consistent and independent of patient age, sex, geographic region, prior lines of treatment or ECOG performance status. In clinical trials, the most frequently reported drug-related adverse events in regorafenib-treated patients versus placebo-treated patients, respectively, were: asthenia/fatigue, hand-foot skin reaction (HFSR) / palmar-plantar erythrodysesthesia (PPE), diarrhea, decreased appetite and food intake, hypertension, mucositis, dysphonia, infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever and nausea. The most serious adverse drug reactions in patients receiving regorafenib are hepatotoxicity, hemorrhage, and gastrointestinal perforation. Adverse events in regorafenib-treated patients generally occur early (within the first two treatment cycles), therefore it is advised to monitor patients closely. Full results from the GRID study were presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June 2012 and published in November 2012 in The Lancet. Regorafenib has been approved under the brand name Stivarga in several countries, including the U.S. and Japan, for the treatment of GIST. In 60 countries worldwide, including the U.S., Europe and Japan, the product has also been approved for the treatment of patients with metastatic colorectal cancer (mCRC). About the GRID Study GRID (GIST – Regorafenib In Progressive Disease) was a randomized, double-blind, placebo-controlled, multi-center Phase III study of regorafenib for the treatment of GIST. It randomized 199 patients whose disease had progressed despite prior treatment with imatinib and sunitinib. Patients were randomized in a 2:1 ratio to receive either regorafenib plus BSC or placebo plus BSC to evaluate efficacy and safety. Treatment cycles consisted of 160 mg regorafenib (or matching placebo) once daily for three weeks on / one week off plus BSC. The primary endpoint was PFS, and secondary endpoints included OS, time to progression, disease control rate, tumor response rate, and duration of response. The safety and tolerability of the two treatment groups were also compared. Patients initially randomized to placebo were allowed to cross over to open-label regorafenib once the disease progressed.

On July 30, 2014 AstraZeneca reported that it has entered into a clinical study collaboration with Kyowa Hakko Kirin for a Phase I/Ib immuno-oncology study that will evaluate the safety and efficacy of two separate combinations of three investigational compounds in multiple solid tumours (Press release AstraZeneca, JUL 29, 2014, View Source;astrazeneca-and-kyowa-hakko-kirin-partner-on-immuno-oncology-clinical-study [SID:1234500667]).

The study will evaluate AstraZeneca’s anti-PD-L1 antibody, MEDI4736, in combination with Kyowa Hakko Kirin’s anti-CCR4 antibody, mogamulizumab, and AstraZeneca’s anti-CTLA-4 antibody tremelimumab, in combination with mogamulizumab.

MEDI4736, tremelimumab, and mogamulizumab are part of a new class of cancer treatments known as immunotherapies, which use the body’s own immune system to help fight cancer. MEDI4736 and tremelimumab block the signals that help tumours avoid detection by the immune system, while mogamulizumab suppresses some of the immune cells that shield the tumour from the immune system.

Under the terms of the agreement, AstraZeneca and Kyowa Hakko Kirin will co-fund the study, which will be conducted by Kyowa Hakko Kirin. The Phase I part of the study is expected to establish a recommended dose regimen and Phase Ib will assess the safety and efficacy of the two combinations. Results from these studies will determine the future clinical development of the combinations.

Briggs Morrison, Executive Vice President, Global Medicines Development & Chief Medical Officer, AstraZeneca, said: “We believe that combination therapy in immuno-oncology has the potential to be one of the most effective ways of treating cancer. Our partnership with Kyowa Hakko Kirin provides the opportunity to explore two novel and exciting combinations.”

“With recent progress in the field of cancer immunotherapy, we have the potential to bring significant benefits to patients,” said Yoichi Sato, Managing Executive Officer, Vice President, Head of Research and Development Division of Kyowa Hakko Kirin. “Given the potential synergistic activity of our anti-CCR4 antibody when combined with immune checkpoint inhibitors, we look forward to collaborating with AstraZeneca to explore these combinations in multiple types of cancer.”

AstraZeneca and MedImmune have a broad programme of immuno-oncology combination trials underway, including MEDI4736 with Incyte’s oral indoleamine dioxygenase-1 (IDO1) inhibitor, INCB24360 and MEDI4736 with Advaxis’ immunotherapy vaccine, ADXS-HPV.