On June 29, 2015 CytRx reported the presentation of interim results from its ongoing open-label Phase 2 pilot study evaluating the efficacy and safety of aldoxorubicin for the treatment of Kaposi’s Sarcoma (KS) in HIV-infected patients (Press release, CytRx, JUN 29, 2015, View Source [SID:1234506004]). The data will be presented on Wednesday, July 1, 2015 during a poster session at the 18th International Workshop on Kaposi’s Sarcoma Herpesvirus (KSHV) and Related Agents in Hollywood, Florida. Schedule your 30 min Free 1stOncology Demo! For the study, patients with biopsy-confirmed KS were administered 100 or 150 mg/m2 aldoxorubicin (75 or 112 mg/m2 doxorubicin equivalents) IV every three weeks. At the time of presentation, preliminary analyses were available for nine patients who received at least six cycles of drug (mean = 6.3 cycles). Four patients had received prior Doxil chemotherapy. Of these 9 patients, 6 (67%) demonstrated a partial response (PR) to aldoxorubicin at the end of study visit (EOS), and 7 (78%) demonstrated PR within 4 months of EOS. Doxorubicin could be detected in all tumor biopsies and higher doxorubicin concentrations were demonstrated within KS lesions relative to skin next to the lesions for 3/4 (75%) patients for whom adequate tissue was available for analysis. Five of 6 (83%) patients receiving aldoxorubicin and for whom data are available exhibited reduced intratumoral viral loads during therapy. A subset of patients also exhibited improvements in quality of life during treatment, and all patients exhibited either improvement or stability in immunologic and virologic HIV treatment parameters. Aldoxorubicin was well-tolerated, with only 2 patients (22%) experiencing a grade 4 adverse event (transient neutropenia and anemia), and overall AEs (44%) were mild and compared favorably with AE rates from other trials enrolling KS patients representing urban, minority-predominant populations.
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"KS remains an important cause of morbidity and mortality for HIV-infected patients worldwide, yet significant toxicities limit drug exposure and outcomes for many patients when antiretroviral therapy is combined with standard treatments like liposomal doxorubicin (Doxil)," said Chris Parsons, MD, Associate Professor in the Departments of Medicine and Microbiology, Immunology, & Parasitology at the Louisiana State University Health Sciences Center, and principal investigator of the study. "These data demonstrate aldoxorubicin’s ability to leverage cancer biology to preferentially release chemotherapeutic drugs in tumors, thereby limiting toxicity, increasing drug exposure and improving outcomes. We remain highly encouraged by the activity and tolerability of aldoxorubicin in this study, and look forward to its continued enrollment and final results."
This open-label Phase 2 clinical trial is expected to enroll up to 30 patients, randomly assigned to two equally sized treatment arms which will receive aldoxorubicin at 100 or 150 mg/m2 by 30-minute intravenous infusion. Because the KS patients in the study have compromised immune systems, the aldoxorubicin dosages administered in the trial are lower than those administered in the Company’s clinical testing of aldoxorubicin in patients with soft tissue sarcomas. Patients with advanced KS receive aldoxorubicin on day 1, then every 3 weeks until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. The primary objectives of preliminary efficacy include evaluation of the size, number and nodularity of skin lesions, change in size and number of lung lesions and changes in the number of tumor cells that express viral DNA (Kaposi sarcoma-associated herpesvirus, the etiologic agent of KS). The Company is also evaluating the level of aldoxorubicin uptake into lesions. Safety is being assessed through monitoring of adverse events and the ability to remain on assigned treatment. The trial is being conducted at the Louisiana State University Health Sciences Center in New Orleans, LA.
KS is an orphan indication in the U.S.
About Kaposi’s Sarcoma
Kaposi sarcoma is a cancer that causes lesions (abnormal tissue) to grow in the skin; the mucous membranes lining the mouth, nose, and throat; lymph nodes; or other organs. The lesions are usually purple and are made of cancer cells, new blood vessels, red blood cells, and white blood cells. Kaposi sarcoma is different from other cancers in that lesions may begin in more than one place in the body at the same time. KS remains the most common HIV-associated tumor worldwide. The condition is also endemic in certain parts of Central Africa and Central and Eastern Europe.
About Aldoxorubicin
The widely used chemotherapeutic agent doxorubicin is delivered systemically and is highly toxic, which limits its dose to a level below its maximum therapeutic benefit. Doxorubicin also is associated with many side effects, especially the potential for damage to heart muscle at cumulative doses greater than 450 mg/m2. Aldoxorubicin combines doxorubicin with a novel single-molecule linker that binds directly and specifically to circulating albumin, the most plentiful protein in the bloodstream. Protein-hungry tumors concentrate albumin, thus increasing the delivery of the linker molecule with the attached doxorubicin to tumor sites. In the acidic environment of the tumor, but not the neutral environment of healthy tissues, doxorubicin is released. This allows for greater doses (3 ½ to 4 times) of doxorubicin to be administered while reducing its toxic side effects. In studies thus far there has been no evidence of clinically significant effects of aldoxorubicin on heart muscle, even at cumulative doses of drug well in excess of 2,000 mg/m2.
Independent Data Safety and Monitoring Board Recommends Continuation of Celldex’s Phase 3 Study of RINTEGA(R) (rindopepimut) in Newly Diagnosed Glioblastoma
On June 29, 2015 Celldex Therapeutics that an independent Data Safety and Monitoring Board (DSMB) recommended continuation of the Phase 3 ACT IV study of RINTEGA (rindopepimut) in patients with newly diagnosed glioblastoma (Press release, Celldex Therapeutics, JUN 29, 2015, View Source [SID:1234506002]). Schedule your 30 min Free 1stOncology Demo! The ACT IV study is a randomized, double-blind, placebo controlled study of rindopepimut plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. 745 patients were enrolled into ACT IV to reach the required 374 patients with minimal residual disease (assessed by central review) needed for analysis of the primary overall survival endpoint. All patients, including those with disease that exceed this threshold, will be included in a secondary analysis of overall survival as well as analyses of progression-free survival, safety and tolerability, and quality of life. The timing of the overall survival primary endpoint data is event-driven. Interim analyses assessing safety, futility and efficacy conducted by an independent DSMB were prespecified at 50 percent and 75 percent of events. Know more, wherever you are: As previously announced, the second interim analysis is expected to occur in late 2015/early 2016.
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RINTEGA is a registered trademark of Celldex Therapeutics.
About RINTEGA
RINTEGA is an investigational therapeutic vaccine that targets the tumor specific oncogene EGFRvIII, a functional and permanently activated variant of the epidermal growth factor receptor (EGFR), a protein that has been well validated as a target for cancer therapy. Expression of EGFRvIII correlates with increased tumorigenicity in mouse models and poor long term survival in clinical studies of patients with glioblastoma (GBM). In addition, EGFRvIII-positive cells are believed to stimulate proliferation of non-EGFRvIII cells through IL-6 cell-to-cell signaling and to release microvesicles containing EGFRvIII, which can merge with neighboring cells, transferring tumor-promoting activity. EGFRvIII expression may also be associated with tumor stem cells that have been identified in GBM. These stem cells contribute to resistance to cytotoxic therapy and tumor recurrence. EGFRvIII is expressed in tumors in about 30% of patients with GBM. It has not been detected at a significant level in normal tissues; therefore, targeting of this tumor-specific molecule is not likely to impact healthy tissues.
Three Phase 2 trials of RINTEGA—ACTIVATE, ACT II, and ACT III—have been conducted in newly diagnosed EGFRvIII-positive GBM and have shown consistent improvements in both overall survival and progression-free survival compared to matched historical controls. The most common adverse events for RINTEGA include injection site reactions, fatigue, rash, nausea and pruritus. RINTEGA is currently being studied in two clinical trials in EGFRvIII-positive GBM—an international Phase 3 study called ACT IV in newly diagnosed GBM and a Phase 2 study called ReACT in recurrent GBM. In February 2015, the U.S. Food and Drug Administration (FDA) granted RINTEGA Breakthrough Therapy Designation for the treatment of adult patients with EGFRvIII-positive glioblastoma (GBM).
Lilly and Immunocore Announce Immunotherapy-based Clinical Trial Collaboration in Melanoma
On June 29, 2015 Eli Lilly and Immunocore reported that they have entered into an immunotherapy-based clinical trial collaboration to explore the utility of Immunocore’s lead T cell receptor-based investigational therapeutic, IMCgp100, in combination with Lilly’s galunisertib (LY2157299) and merestinib (LY2801653) for the treatment of melanoma (Press release, Eli Lilly, JUN 29, 2015, View Source [SID:1234506000]). The goal of the collaboration is to identify combination regimens that provide synergies in efficacy and durability in patients with metastatic cutaneous and uveal melanomas. Schedule your 30 min Free 1stOncology Demo! Under the terms of the agreement, Immunocore and Lilly will conduct a Phase Ib/II clinical study evaluating the safety and preliminary efficacy of IMCgp100 in combination with galunisertib in metastatic cutaneous melanoma. A second Phase Ib/II study will be conducted combining IMCgp100 with merestinib in metastatic uveal melanoma. Lilly will act as trial sponsor. These studies are anticipated to begin in 2016. No financial terms were disclosed. Know more, wherever you are: IMCgp100 and galunisertib are members of a new class of cancer treatments known as immunotherapies, which are designed to enhance the body’s own immune system in fighting cancer and whose mechanisms of action have the potential to be complementary. IMCgp100 is Immunocore’s most advanced Immune mobilizing mTCR Against Cancer molecules (ImmTAC), which are a novel class of bi-specific biologic drugs based on T cell receptors (TCRs) with ultra-high affinity for intracellular and extracellular cancer targets. Lilly’s galunisertib is a small molecule inhibitor of TGF beta R1 kinase that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumor growth, suppresses the immune system and increases the ability of tumors to spread in the body. Merestinib is Lilly’s small molecule multi-kinase inhibitor that in vitro selectively blocks signaling of MET, MST1R (RON), AXL, and MKNK1/2, pathways that potentially play a role in metastatic uveal melanoma. Know more, wherever you are: "This collaboration with Immunocore underscores Lilly’s commitment to discovering the potential of combination therapies, which will be key to the future of cancer care for people fighting diseases such as melanoma," said Richard Gaynor, M.D., senior vice president, product development and medical affairs for Lilly Oncology. "Lilly is building a robust portfolio of potential advances in immunotherapy through our own research as well as with strategic collaborations like Immunocore."
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Immunocore and Lilly entered into a co-discovery and co-development collaboration, announced in July 2014, to research and potentially develop other novel T cell-based cancer therapies built on Immunocore’s ImmTAC platform.
"We are very pleased to be able to announce a second collaboration with Lilly after entering into a collaboration last year," said Eliot Forster, chief executive officer of Immunocore. "Combining our ImmTAC, IMCgp100 with Lilly’s galunisertib and merestinib has the potential to transform the treatment of metastatic cutaneous and uveal melanoma. Immunocore is committed to the development of IMCgp100 in metastatic uveal and cutaneous melanoma where there is such great unmet medical need."
Immunocore recently announced clinical efficacy data in a Phase I/IIa trial with IMCgp100 in patients with advanced melanoma, as well as in the expansion cohort with uveal melanoma.
About Melanoma
Melanoma is a cancer that begins in the melanocytes. Other names for this cancer include malignant melanoma and cutaneous melanoma. Most melanoma cells still make melanin, so melanoma tumors are usually brown or black. But some melanomas do not make melanin and can appear pink, tan, or even white.
Melanomas can develop anywhere on the skin, but they are more likely to start on the trunk (chest and back) in men and on the legs in women. The neck and face are other common sites.
Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Like basal cell and squamous cell cancers, melanoma is almost always curable in its early stages. But it is much more likely than basal or squamous cell cancer to spread to other parts of the body if not caught early.[i]
According to the American Cancer Society’s estimates for melanoma in the United States for 2015, about 73,870 new melanomas will be diagnosed (about 42,670 in men and 31,200 in women); and about 9,940 people are expected to die of melanoma (about 6,640 men and 3,300 women).[ii]
Uveal (or ocular) melanoma is a cancer of the eye diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5-7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year.[iii]
About IMCgp100 and ImmTACs
Immunocore’s proprietary technology is focused on small protein molecules called ImmTACs (Immune mobilizing mTCR Against Cancer) that enable the immune system to recognize and kill cancerous cells.
Immunocore’s ImmTACs, a new class of drug with ultra-high affinity for intracellular cancer targets, are synthetic, soluble T cell receptors (TCRs) that recognize diseased cells containing disease specific targets. The ImmTACs enable circulating T cells to selectively identify and kill diseased cells. The ImmTAC platform is unique and has very high specificity and potency as well as broad applicability to a wide range of intracellular targets. ImmTACs can access up to nine-fold more targets than typical antibody-based therapies, including monoclonal antibodies.
TCRs naturally recognize diseased cells and Immunocore’s world-leading competitive advantage is its ability to engineer high affinity TCRs and link them to an antibody fragment that activates a highly potent and specific T cell response to recognize and destroy cancer cells.
The most advanced ImmTAC, IMCgp100, is currently in Phase IIa clinical trials for the treatment of late stage melanoma. Following completion of a Phase I study at the end of 2013, Immunocore initiated a Phase IIa study to optimize the dosing regimen of IMCgp100. Immunocore has a growing internal pipeline of ImmTACs addressing many different cancer types and has developed a broad database of intracellular cancer targets.
About Galunisertib (LY2157299)
Galunisertib is a TGF beta R1 kinase inhibitor that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumor growth, suppresses the immune system and increases the ability of tumors to spread in the body.
About Merestinib (LY2801653)
Merestinib is Lilly’s multi-kinase inhibitor that in vitro selectively blocks signaling of MET, MST1R (RON), AXL, and MKNK1/2.
The Leukemia & Lymphoma Society Accelerates Milestone Payment Associated with the Phase 3 Study of CPX-351 in High Risk (Secondary) AML
On June 29, 2015 Celator Pharmaceuticals reported that The Leukemia & Lymphoma Society (LLS) is accelerating a portion of the final payment linked to the Phase 3 study of CPX-351 (cytarabine:daunorubicin) liposome injection, Celator’s lead product candidate, for the treatment of patients with high-risk (secondary) acute myeloid leukemia (AML) (Press release, Celator Pharmaceuticals, JUN 29, 2015, View Source [SID:1234505999]). Schedule your 30 min Free 1stOncology Demo! LLS has moved forward payment of $400,000 originally attached to the final overall survival analysis milestone and added it to the milestone payment for induction response rate analysis, thereby increasing the payment from the original amount of $500,000 to $900,000. This brings the total LLS funding paid to date associated with the Phase 3 study to $4.9 million.
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The financial support provided by the LLS Therapy Acceleration Program (TAP) has been important in expediting the completion of the Phase 3, multicenter trial of CPX-351 versus conventional cytarabine plus daunorubicin in older patients with untreated high risk (secondary) AML. Enrollment in the study was completed ahead of schedule, and positive induction response results were announced earlier this month. The overall survival results, the primary endpoint of the study, are expected in the first quarter of 2016. This study is planned to support a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) expected in the second half of 2016.
"We continue to be very pleased with the progress and positive outcomes Celator has achieved with the development of CPX-351," said Louis DeGennaro, Ph.D., LLS’s chief executive officer. "We felt it appropriate to accelerate our payments to assist Celator in completing the activities necessary to file the NDA with the FDA as soon as possible once the overall survival data become available. We are optimistic for a successful outcome of the Phase 3 study and want to help accelerate the availability of promising therapies such as CPX-351 to these patients who are in dire need of improved outcomes."
As part of a 2009 partnership, LLS provided $4.1 million to help fund Celator’s Phase 2 clinical development program, which included two randomized, controlled studies. The positive results from those two studies were used to help design the current Phase 3 study. LLS’s TAP program supports private sector and academic-based projects with the goal of advancing investigational therapies with high prospects for providing near-term benefit to patients with blood cancers.
"This additional funding comes at an opportune time," said Scott Jackson, Celator’s chief executive officer. "With the recent announcement of positive induction response rate results for our Phase 3 study, we continue to move forward with our preparations for an NDA filing and ultimately commercialization of CPX-351 in the United States. These activities will benefit from the earlier availability of TAP funds and with positive overall survival results in our Phase 3 study, CPX-351 will be available to AML patients as soon as possible. Our partnership with LLS, which began back in 2008, has been extremely productive towards that end."
About CPX-351
CPX-351 (cytarabine:daunorubicin) Liposome for Injection represents an innovative approach to developing combinations of drugs, in which drug molar ratios with synergistic anti-tumor activity are co-encapsulated in a drug delivery vehicle in order to maintain the desired ratio following administration. CPX-351 has been granted orphan drug status by the U.S. Food and Drug Administration and the European Commission for the treatment of Acute Myeloid Leukemia (AML). Celator has conducted two randomized, controlled, Phase 2 studies with CPX-351. The first study was conducted in newly diagnosed elderly AML patients and the second study was conducted in patients with AML in first relapse. In both Phase 2 studies, treatment with CPX-351 resulted in significant improvements in response rates, 60-day mortality, and overall survival in the highest risk patients. The Leukemia & Lymphoma Society has partnered with Celator in the development of CPX-351 starting in Phase 2 and continuing in Phase 3.
About Acute Myeloid Leukemia (AML)
LLS defines AML as a quickly progressing disease in which too many immature white blood cells (not lymphocytes) are found in the blood and bone marrow. According to Cancer Facts and Figures, in 2015 approximately 20,830 new cases of AML will be diagnosed in the United States and 10,460 deaths will occur from the disease.
About The Leukemia & Lymphoma Society
The Leukemia & Lymphoma Society (LLS) is the world’s largest voluntary health agency dedicated to blood cancer. The LLS mission: Cure leukemia, lymphoma, multiple myeloma, and improve the quality of life of patients and their families. LLS funds lifesaving blood cancer research around the world, provides free information and support services, and is the voice for all blood cancer patients seeking access to quality, affordable, coordinated care.
4SC’s partner Yakult Honsha enters with cancer compound resminostat further
indications and starts clinical Phase I study in patients with pancreatic or
biliary tract cancer in Japan
On June 26, 2015 4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for cancer and autoimmune diseases, reported that the first patient has been treated with resminostat in a Japan-based Phase I clinical study conducted by 4SC’s exclusive Japanese partner Yakult Honsha (Press release, 4SC, JUN 26, 2015, View Source [SID:1234506545]). The multi-centre open-label study will investigate safety, pharmacokinetics, biomarkers and efficacy of various dose regimens of resminostat in monotherapy or in combination with the S-1 chemotherapy in up to 44 Japanese patients with advanced pancreatic or biliary tract cancer. The main goal of the study is to determine the recommended regimen for subsequent Phase II trials in these indications.
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In Part 1 of the study, dose limiting toxicities (DLTs) of various dose regimens of resminostat in monotherapy and the resminostat/S-1 combination therapy will be determined in up to 24 patients. In Part 2, the tolerability and safety of the regimen/s selected in Part 1 will be further evaluated in 20 additional patients in order to determine the recommended regimen/s for subsequent Phase II studies. Furthermore, the study will investigate pharmacokinetics, biomarkers and efficacy criteria including best overall response, progression-free survival (PFS), and overall survival (OS).
The overall development rationale behind the study is to test the epigenetic agent resminostat in further gastrointestinal indications and in particular in combination with the S-1 chemotherapy, which is approved for the treatment of pancreatic and biliary tract cancer in Japan. S-1 contains a prodrug of the chemotherapeutic agent 5-FU. Resminostat has already been tested clinically in a Phase I study in combination with the 5-FU-based FOLFIRI chemotherapy regimen in Western patients with colorectal cancer. The administration of resminostat in combination with the standard FOLFIRI regimen was well tolerated without any dose limiting toxicity. Moreover in preclinical models, resminostat has shown first positive results in pancreatic and biliary tract cancer. 2
Enno Spillner, Chief Executive Officer of 4SC AG, said: "We very much appreciate that our partner Yakult Honsha has started developing resminostat in combination therapy with an established cancer drug in additional two gastrointestinal solid cancer indications in Japan. There is high unmet medical need in both pancreatic and biliary tract cancer. These new indications are a perfect match to the ongoing Phase II trials by Yakult investigating resminostat in combination therapies in the indications liver cancer (HCC) and non-small-cell lung cancer (NSCLC). While Yakult is evaluating resminostat in a number of mostly gastrointestinal solid cancer indications in Asian patients, 4SC intends to focus, as the immediate next step, on developing resminostat in the heamatological indication of CTCL in Europe where we also see a high medical need and an attractive opportunity for a fast-tomarket option for resminostat. We are currently preparing a European Phase II study in CTCL."
About pancreatic cancer and biliary tract cancer
Pancreatic cancer is characterized as a disease with some of the highest unmet need in oncology. is The disease is responsible for 331,000 deaths per year, and is thus the seventh most common cause cancer-related mortality in both sexes combined. Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 months and a five-year survival rate of below 5%, representing one of the poorest prognoses across gastrointestinal (GI) cancers. Approved drugs for first line setting in Western countries comprise the chemotherapies gemcitabine and FOLFIRINOX. In Japan, S-1 has been approved for the treatment of pancreatic cancer since 2006.
Primary bile duct cancer is a relatively rare cancer, however, with the number of new cases increasing. In Japan, the incidence of biliary tract cancer and intrahepatic bile duct cancer is about 10 out of every 100,000 people, which is higher than the incidences in other countries. These cancers typically have a poor prognosis, with 5-year survival rates in the range of 5% to 15%. In Japan, chemotherapies gemcitabine, cisplatin and S-1 have been used in this indication.
About resminostat
Resminostat (4SC-201) is an oral protein-deacetylase (HDAC) inhibitor with an innovative epigenetic mechanism of action that potentially enables the compound to be deployed as a novel, targeted tumour therapy for a broad spectrum of oncological indications, both in monotherapy and, in particular, in combination with other cancer drugs. Like other epigenetic therapies, resminostat modifies transcription of genes in cancer cells and, thereby, reprograms the phenotypes of such cancer cells. Additionally, resminostat has immunotherapeutic effects by activating NK cells, restoring MHCI and MHCII proteins and suppression of unspecific immunosuppression. Resminostat is assumed to be able to halt tumour progression and induce tumour regression. Furthermore, due to its epigenetic 3 mode of action resminostat is supposed to develop additional synergetic effects when combined with classical cancer therapies and to counteract the development of tumour cell resistance. For example, in preclinical trials, resminostat has been shown to effectively inhibit epithelial-mesenchymal transition (EMT). EMT, which may be promoted through the administration of certain conventional cancer therapies, leads to the formation of particularly aggressive tumour cells, which ultimately may result in greater proliferation of cancer cells in patients and the patients’ death. On the whole, a reinforcing positive therapeutic effect is expected to be achieved through a well-tolerated combination of a traditional cancer therapy with an epigenetic compound such as resminostat.
Resminostat – by 4SC and its Japanese partner Yakult – has been investigated in a broad clinical campaign comprising liver cancer (hepatocellular carcinoma, HCC), Hodgkin’s Lymphoma (HL), colorectal cancer (CRC), and non-small-cell lung cancer (NSCLC). In the Phase II SAPHIRE trial in patients with advanced Hodgkin’s Lymphoma (HL), resminostat monotherapy has demonstrated antitumour activity, with an overall response rate of 34% and a clinical benefit in 54% of the patients in a heavily pre-treated patient population together with very good safety and tolerability. In the Phase IIa SHELTER study resminostat has been evaluated as monotherapy and in combination with sorafenib as a second-line treatment in advanced Western HCC patients after proven radiological disease progression under first-line sorafenib therapy. Patients receiving the resminostat/sorafenib combination therapy showed a median overall survival of 8.0 months and a progression-free survival rate (PFSR) after 12 weeks of 62.5% and a median time-to-progression (TTP) of 6.5 months. Notably, in both tumour indications, HCC and HL, gene expression levels of the new biomarker ZFP64 measured prior to study treatment start in blood cells of patients, were identified to be potentially indicative of survival outcome upon treatment with resminostat. Hereby, the set of patients with a high level of ZFP64 gene expression at baseline showed a statistically significant increase of median overall survival compared with patients with low ZFP64 expression levels. Resminostat was further studied in a Phase I dose escalation approach in advanced colorectal cancer (CRC) patients evaluating resminostat in combination with the standard chemotherapeutic FOLFIRI regimen. Positive results for safety and tolerability as well as promising signs of clinical activity of this combination were published at the 2013 ASCO (Free ASCO Whitepaper) conference. Yakult Honsha is currently developing resminiostat in two randomised clinical Phase II trials in Asian patients in HCC and NSCLC and in a Phase I trial in patients with pancreatic and biliary tract cancer. Resminostat is partnered with Yakult Honsha for Japan and with Menarini in the Asia Pacific (APAC) region excluding Japan. 4SC is currently in preparations of a randomised, controlled Phase II trial in the indication of advanced cutaneous T-cell lymphoma (CTCL) in Europe.
About the resminostat partnering agreement with Yakult Honsha for Japan
4SC granted an exclusive license to Yakult Honsha for the development and commercialization of resminostat in Japan in April 2011. 4SC has received an upfront payment from Yakult Honsha of €6 million and is eligible for up to approximately €127 million payable upon achieving specified milestones 4 including clinical and regulatory events in Japan. In addition to milestone payments, Yakult will pay 4SC double-digit royalties linked to product sales of resminostat. Yakult Honsha will be responsible for all clinical requirements for resminostat development in Japan in oncology indications. 4SC is aiming to partner this compound in other territories, including Europe and the USA.