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Celsion Announces Data Monitoring Committee Unanimously Recommends Continuation of Phase III OPTIMA Study of ThermoDox® for Primary Liver Cancer

On November 30, 2016 Celsion Corporation (NASDAQ:CLSN) reported that following a review of data from its multinational, randomized pivotal Phase III clinical study of ThermoDox in combination with optimized radiofrequency ablation (RFA) for primary liver cancer (the OPTIMA Study), the study’s Data Monitoring Committee (DMC) has unanimously recommended that the trial continue enrollment. With approximately 40% of patients currently enrolled in the trial, Celsion expects to complete patient enrollment in this 550 patient trial by early 2018 (Press release, Celsion, NOV 30, 2016, View Source [SID1234516849]).

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"Following the recent presentation by the NIH confirming our hypothesis that ThermoDox in combination with optimized RFA can be a treatment with curative intent for HCC, we could not be more pleased that the DMC has recommended continuation of the OPTIMA Study without modification. Based on their review of all the available study data, the DMC has concluded that ThermoDox is safe for newly diagnosed, intermediate stage patients and that the study is being conducted according to the highest of clinical research standards," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We remain optimistic and encouraged by this decision, and by the potential that ThermoDox has consistently demonstrated in patients with primary liver cancer, a patient population in dire need of new therapeutic options."

The DMC is comprised of an independent group of medical and scientific experts and is responsible for reviewing and evaluating patient safety and efficacy data for the Company’s Phase III OPTIMA Study. The DMC reviews study data at regular intervals in order to ensure the safety of all patients enrolled in the trial and to monitor the quality and overall conduct of the trial including each site’s compliance with the minimum RFA heating time of 45 minutes specified in the study protocol. The OPTIMA Study’s design and statistical plan calls for two interim analyses by the DMC with the intent of evaluating its safety and efficacy to determine if there is overwhelming evidence of clinical benefit or a low probability of treatment success (a futility analysis) to continue, modify or terminate the trial.

On November 29, 2016, the Company announced results from an independent retrospective analysis conducted by the National Institutes of Health (NIH) on the intent-to-treat population of the 701 patient HEAT Study of ThermoDox plus optimized RFA for the treatment of primary liver cancer. The NIH analysis, which sought to evaluate the correlation between RFA burn time per tumor volume (min/ml) and clinical outcome, concluded that increased burn time per tumor volume significantly improved overall survival (OS) in patients with solitary lesions treated with RFA + ThermoDox compared to patients treated with RFA alone. The NIH analysis included 437 patients with a single lesion from the Company’s HEAT Study, the same patient population being treated in the Company’s ongoing Phase III OPTIMA study. These findings are consistent with Celsion’s own analysis of the HEAT Study data, which demonstrated that over a 3.5 year period, there was a statistically significant two year survival benefit for patients treated with ThermoDox plus optimized RFA over the optimized RFA only group.

About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 75 clinical sites in the United States, Europe, China and Asia Pacific, and will evaluate ThermoDox in combination with optimized RFA, which will be standardized to a minimum of 45 minutes across all investigators and clinical sites for treating lesions three to seven centimeters, versus standardized RFA alone. The primary endpoint for the trial is Overall Survival, which is supported by post-hoc analysis of data from the Company’s 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when combined with ThermoDox. The statistical plan calls for two interim efficacy analyses by an independent Data Monitoring Committee (iDMC).

Pfizer Announces Positive Top-Line Results from the Pivotal Comparative REFLECTIONS B3271002 Study for PF-05280014, a Potential Biosimilar to Herceptin®1 (trastuzumab)

On November 30, 2016 Pfizer Inc. (NYSE:PFE) reported that the pivotal REFLECTIONS B3271002 study, a comparative safety and efficacy study of PF-05280014 versus Herceptin (trastuzumab), met its primary endpoint (Press release, Pfizer, NOV 30, 2016, View Source [SID1234516846]). PF-05280014 is being developed by Pfizer as a potential biosimilar to Herceptin.

The trial demonstrated equivalence in the primary endpoint of objective response rate (ORR) of PF-05280014 versus Herceptin, taken in combination with paclitaxel, in first line patients with HER2-positive metastatic breast cancer. ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum period of time2.

"As the leading global biosimilars company, we are committed to advancing our robust pipeline of biosimilar therapies in hopes of expanding access to high-quality treatment options for patients living with serious, life-threatening conditions such as cancer," said Sumant Ramachandra, MD, PhD, MBA, Head of Research and Development, Pfizer Essential Health. "Favorable comparative clinical data between proposed biosimilars and their respective reference product contribute to physician and patient understanding of and confidence in the value and importance of biosimilars. We are encouraged by these data and look forward to sharing the complete results with health authorities and the oncology community once available."

A separate comparative, randomized, double-blind clinical trial [REFLECTIONS B3271004] in early breast cancer patients [N=226] also met its primary endpoint of steady-state Ctrough concentrations (PK) in patients treated with PF-05280014 and Herceptin.

About the REFLECTIONS B3271002 Study

REFLECTIONS B3271002 is a comparative, randomized, double blind, clinical trial[N=690] evaluating the efficacy, safety, pharmacokinetics (PK) and immunogenicity of PF-05280014 (a potential biosimilar to Herceptin [trastuzumab]) in combination with paclitaxel versus Herceptin in combination with paclitaxel in first line patients with HER2-positive metastatic breast cancer. The primary endpoint is objective response rate (ORR) by Week 25 of study treatment. ORR is defined as the proportion of patients with tumor size reduction of a predefined amount and for a minimum period of time2.

More information about the PF-05280014 REFLECTIONS B3271002 and B3271004 studies can be found at www.clinicaltrials.gov (link is external).

About PF-05280014

PF-05280014 is a monoclonal antibody (mAb) that is in development as a potential biosimilar for all currently approved indications of Herceptin (trastuzumab).

Herceptin is currently approved in the U.S., EU and other markets for HER2-positive breast cancer and gastric cancer.

PF-05280014 is an investigational compound and has not received regulatory approval in any country. Biosimilarity has not yet been established by regulatory authorities and is not yet claimed.

First clinical data for monalizumab as a single agent in cancer patients show favorable safety profile

On November 30, 2016 Innate Pharma SA (the "Company" – Euronext Paris: FR0010331421 – IPH) reported preliminary safety results from the dose-ranging part of a Phase I/II trial investigating monalizumab as a single agent in patients with advanced gynecologic malignancies (Press release, Innate Pharma, NOV 30, 2016, View Source [SID1234516844]).

The data are presented today as a poster at the EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium (Munich, Germany) 10:15 a.m. – 5:00 p.m. CET and will be discussed by Dr Anna Tinker, Medical Oncologist (British Columbia Cancer Agency, Vancouver) on behalf of CCTG during the Spotlight session at 1:10 – 1:20 p.m. CET. Monalizumab is Innate Pharma’s first-in-class anti-NKG2A antibody partnered with AstraZeneca. The trial is sponsored and conducted by the Canadian Cancer Trials Group (CCTG).

In this dose-ranging part of the study, 18 patients with advanced, heavily pretreated ovarian cancer were randomized to receive three dose levels of monalizumab (1, 4 and 10 mg/kg, every two weeks – six patients at each dose level). The data showed that monalizumab was well tolerated in this patient population, with no dose-limiting toxicities observed. No major differences in terms of safety were observed across the different dose levels. The most common adverse events (AEs) reported include fatigue and headaches. AEs were mostly low grade and rarely resulted in treatment delays. Preliminary efficacy data showed short-term disease stabilization in 41% of patients, including one patient with a mixed response.

Lesley Seymour, MD, PhD, Professor in Oncology at Queen’s University in Kingston, Ontario and Director of the Investigational New Drug Program at CCTG, said: "Monalizumab was well tolerated in this patient population with advanced gynecologic malignancies. These refractory tumors are an area of unmet need, and are typically treated with cytotoxic chemotherapy which is often poorly tolerated. Building on these initial results, further investigation of monalizumab in these patients is warranted and we are therefore continuing to enroll patients with relapsed and refractory gynecologic malignancies into the expansion phase of the study."

Pierre Dodion, Chief Medical Officer of Innate Pharma, said: "These are the first clinical data reported with monalizumab in cancer patients and they suggest a favorable safety profile. Preliminary results support the continuation of the ongoing cohort expansion part of this study and we look forward to its results. A comprehensive exploratory clinical plan investigating monalizumab in several indications, as both a monotherapy and combination treatment, is underway. We look forward to reporting further data as we move into 2017."

The cohort expansion part of this trial (up to 98 patients) is ongoing at the recommended Phase II dose (10 mg/kg) in patients with platinum sensitive ovarian cancer, platinum-resistant ovarian cancer, epithelial endometrial cancer and squamous cell carcinoma of the cervix.

Poster Details

Poster title: "Dose ranging study of monalizumab (IPH2201) in patients with gynecologic malignancies: A trial of the Canadian Cancer Trials Group (CCTG): IND221"
Presenter: A. Tinker, Canadian Cancer Trials Group
Location: International Congress Center, Munich, Germany

Agenus Announces Commencement of Phase 1/2 Clinical Trial of anti-OX40 Checkpoint Antibody INCAGN1949 in Patients with Solid Tumors

On November 30, 2016 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune checkpoint antibodies and cancer vaccines, reported that the first patient has been dosed in a Phase 1/2 clinical trial of the anti-OX40 agonist antibody INCAGN1949. The trial is being conducted by, and in collaboration with, Incyte Corporation (Press release, Agenus, NOV 30, 2016, View Source [SID1234516842])

The open-label, dose-escalation portion of the trial will evaluate the safety and tolerability of INCAGN1949 in patients with advanced or metastatic solid tumors and determine its pharmacologically active and/or maximum tolerated dose. Part 2 of the trial is planned to evaluate the recommended dose of INCAGN1949 in multiple tumor types.

"We are pleased with the progress of our fruitful alliance with Incyte and also anticipate advancing a number of Agenus programs outside of the Incyte collaboration, such as our PD-1 antagonist, AGEN2034, into clinical development in the coming months," said Garo H. Armen, Ph.D. Chairman and CEO of Agenus. "Our pipeline of proprietary and differentiated assets continues to offer opportunities for additional partnerships."

INCAGN1949 is an agonist antibody targeting OX40, otherwise known as CD134 or TNFRSF4. OX40 is a co-stimulatory receptor found on activated T cells. OX40 engagement has a two-pronged effect; it can stimulate proliferation of activated T cells that may promote tumor killing and inhibit the activity of regulatory T cells that mediate immune suppression. INCAGN1949 was discovered during an earlier collaboration with Ludwig Cancer Research. This antibody is being co-developed with Incyte.

"Immune checkpoint antibodies including those targeting PD-1/PD-L1 and CTLA-4 have shown clinical activity across multiple tumor types that supported their approval in a number of indications, but a significant proportion of patients are still in need of additional intervention," said Jean-Marie Cuillerot, M.D., VP and Global Head of Clinical Development. "OX40 is an important co-stimulatory checkpoint that contributes to the regulation of the immune anti-tumor response. We believe OX40 agonism provides a robust framework for combination therapy with a potential to make a meaningful difference to patients afflicted by this deadly disease."

Additional information about the trial can be found here.

About Checkpoint Antibodies

Monoclonal antibodies that bind to immune checkpoint receptors, such as CTLA-4 and PD-1, are proven immunotherapeutic targets. These molecules serve as gateways employed by the body to prevent an overt immune response or allow rapid activation of the immune response when needed. Unfortunately, these necessary mechanisms of control can hinder the anti-cancer immune response. They can be harnessed by cancer cells as a defense against immune attack. Agenus is developing a broad pipeline of antibodies that bind to key immune checkpoint proteins and activate or block their activities for use in cancer therapy.

Astex to Showcase Its Next-Generation Hypomethylating Agents Being Developed for Treatment
of AML/MDS at the 2016 Annual Meeting of the American Society of Hematology

On November 29, 2016 Astex Pharmaceuticals, a member of the Otsuka group, reported that investigators collaborating with Astex will present results from several studies evaluating guadecitabine, its subcutaneous, next-generation hypomethylating agent; and ASTX727, its novel, oral hypomethylating agent at the 2016 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego, California, December 3 to 6 (Press release, Astex Pharmaceuticals, NOV 29, 2016, View Source [SID1234516839]).

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The oral presentations are as follows:

Initial results of a Phase 2 Study of Guadecitabine (SGI-110), A Novel Subcutaneous (sc) Hypomethylating Agent, for Patients with Previously Untreated Intermediate-2 or High Risk Myelodysplastic Syndromes (MDS) or Chronic Myelomonocytic Leukemia (CMML) (Abstract #346). Dr. Guillermo Montalban-Bravo et al. Sunday, December 4, 10:15 am; Manchester Grand Hyatt, Grand Hall C.
Results of a Phase II study of Guadecitabine (SGI-110) in higher risk MDS, CMML or low-blast- count AML patients refractory to or relapsing after Azacitidine (AZA) treatment (Abstract #347). Dr. Marie Sebert et al. Sunday, December 4, 10:30 am; Manchester Grand Hyatt, Grand Hall C.
Long Term Survival and Clinical Complete Responses of Various Prognostic Subgroups in 103 Relapsed/Refractory Acute Myeloid Leukemia (r/r AML) Patients Treated with Guadecitabine (SGI-110) in Phase 2 Studies (Abstract #904). Dr. Naval Daver et al. Monday, December 5, 3:30 pm; Marriott Marquis San Diego Marina, San Diego Ballroom AB.
Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 Study (Abstract #114). Dr. Guillermo Garcia-Manero et al. Saturday December 3, 10:45 am; Manchester Grand Hyatt, Grand Hall C.
In addition, a poster presentation entitled: Genetic determinants of response to guadecitabine (SGI-110) in AML (Abstract #1680), Dr. Patricia L. Kropf et al., will be made on Saturday, December 3, 9:30 am to 11 am in the San Diego Convention Center, Hall GH.

Data from the guadecitabine Phase 2 study (www.clinicaltrials.gov, NCT01261312) has helped to inform the design of the 800-patient, global Phase 3 study of guadecitabine in adults with previously untreated AML who are not considered candidates for intensive induction chemotherapy (ASTRAL-1, www.clinicaltrials.gov, NCT02348489), and the newly announced global Phase 3 studies in relapsed / refractory AML (ASTRAL-2, www.clinicaltrials.gov, NCT02920008), and relapsed / refractory MDS or CMML (ASTRAL-3, www.clinicaltrials.gov, NCT02907359). Astex also announced today that enrollment into the ASTRAL-1 study is now complete. The data on ASTX727 being reported at ASH (Free ASH Whitepaper) also informed the design of a Phase 2 randomized, cross-over study comparing ASTX727 to decitabine IV in higher risk MDS, which is ongoing.

"The data from these clinical studies helps to validate the development of these agents for the treatment of AML and MDS, potentially providing new treatment options for patients with these aggressive hematological malignancies," said Mohammad Azab, President and Chief Medical Officer of Astex. "We are delighted to be working with some of the world’s leading experts in the treatment of hematological malignancies in bringing these next-generation therapies to patients."

About Guadecitabine (SGI-110)

Guadecitabine is a novel next-generation, small-molecule DNA hypomethylating agent formulated as a single, small-volume, subcutaneous injection. The product was designed to deliver longer exposure to the active metabolite, decitabine, compared to IV decitabine, and more efficient delivery into key tissues, including the bone marrow. Guadecitabine demonstrated activity in restoring silenced tumor suppressor gene expression in cancer cells by reversal of DNA methylation and inducing responses in previously treated MDS and AML patients. Guadecitabine is currently being investigated in multiple clinical trials, including the ASTRAL series of studies and an extensive program of investigational studies in combination with immunotherapy and other anti-neoplastic agents, for the treatment or a range of hematological malignancies and solid tumors.

About ASTX727

ASTX727 is a unique fixed-dose combination of the hypomethylating agent decitabine, the active ingredient in Dacogen, and the novel cytidine deaminase inhibitor, E7727. ASTX727 was designed to deliver decitabine by oral administration. By inhibiting cytidine deaminase, E7727 inhibits the major mechanism by which decitabine is degraded in the gut, and the combination therefore permits the efficient oral delivery of decitabine at a low dose. Astex is completing a Phase 2 clinical study of ASTX727 in the treatment of intermediate and high risk myelodysplastic syndromes (MDS).

Guadecitabine and ASTX727 are investigational agents, and efficacy and safety have not been established. There is no certainty that these agents will become commercially available.