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]). Schedule your 30 min Free 1stOncology Demo! 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).
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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
Author: [email protected]
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]) Schedule your 30 min Free 1stOncology Demo! 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.
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"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.
Celldex Therapeutics Completes Acquisition of Kolltan Pharmaceuticals
On November 29, 2016 Celldex Therapeutics, Inc. (Nasdaq:CLDX) reported it has completed its previously announced acquisition of Kolltan Pharmaceuticals, Inc., a privately held company focused on the discovery and development of novel, antibody-based drugs targeting receptor tyrosine kinases (RTKs) (Press release, Celldex Therapeutics, NOV 29, 2016, View Source [SID1234516835]).
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"Celldex has added a unique platform of antibodies targeting receptor tyrosine kinases, which are validated targets in oncology, to our pipeline. Clinical and preclinical data suggest these candidates can help overcome tumor resistance mechanisms associated with current tyrosine kinase inhibitors and seen in patients who have failed other cancer therapies," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex. "We believe these programs are highly compatible with our scientific approach and can be developed independently and in combination with Celldex’s existing product candidates. We are finalizing our integrated clinical development strategy and look forward to outlining these plans in the coming weeks."
The following programs have been added to the Celldex pipeline:
CDX-0158 (formerly KTN0158) — a humanized monoclonal antibody that is a potent inhibitor of KIT activation and receptor dimerization in tumor cells and mast cells, which is currently in a Phase 1 dose escalation study in refractory gastrointestinal stromal tumors (GIST).
CDX-3379 (formerly KTN3379) — a human monoclonal antibody designed to block the activity of ErbB3 (HER3), which recently completed a Phase 1b study with combination cohorts where meaningful responses and stable disease were observed in cetuximab (Erbitux) refractory patients in head and neck squamous cell carcinoma and in BRAF-mutant non-small cell lung cancer (NSCLC).
A multi-faceted TAM program — a broad antibody discovery effort underway to generate antibodies that modulate the TAM family of RTKs, comprised of Tyro3, AXL and MerTK, which are expressed on tumor-infiltrating macrophages, dendritic cells and some tumors. Research supports TAMs having broad application and potential across immuno-oncology and inflammatory diseases.
PharmaCyte Biotech Granted FDA Pre-IND Meeting for Pancreatic Cancer Therapy
On November 29, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that a Pre-Investigational New Drug (Pre-IND) meeting with the Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration (FDA) has been granted by the FDA (Press release, PharmaCyte Biotech, NOV 29, 2016, View Source [SID1234516834]). During the meeting with representatives from CBER, they will respond to PharmaCyte’s previously submitted questions to the FDA as part of a Pre-IND information package related to PharmaCyte’s clinical trial in locally advanced, inoperable pancreatic cancer (LAPC).
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PharmaCyte will be submitting a full Pre-IND package of information to the FDA that describes what PharmaCyte intends on submitting in its Investigational New Drug (IND) application. The FDA will review PharmaCyte’s manufacturing, preclinical pharmacology and toxicology and clinical trial plans for the company’s therapy to treat LAPC. After the FDA has responded to the questions and issued comments, PharmaCyte will undertake steps to address them to the FDA’s satisfaction which will lead directly to the preparation of the IND application itself. Once the IND application is found to be acceptable to the FDA, patients can be enrolled in PharmaCyte’s clinical trial.
PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, commented about the Pre-IND meeting saying, "We are pleased that the FDA has granted us a Pre-IND meeting in connection with our planned clinical trial for LAPC patients whose disease has already received maximum response from the gold standard of care – the combination therapy of Abraxane plus gemcitabine. Our Pre-IND meeting is the next step in getting our pancreatic cancer therapy into a clinical trial and approved by the FDA. We believe PharmaCyte is well on its way to accomplishing this goal."
PharmaCyte’s clinical trial in patients with LAPC is designed to meet a clear unmet medical need for those whose cancer no longer responds after 4-6 months of treatment with the combination of Abraxane plus gemcitabine. The trial will be open-label and multi-site in nature, with sites in the U.S. and Europe. Patients with LAPC will be randomized equally into two groups. One group will receive gemcitabine chemotherapy alone, and the other group will receive PharmaCyte’s pancreatic cancer therapy (encapsulated genetically modified live human cells that can activate the cancer prodrug ifosfamide plus low doses of the prodrug to eliminate side effects from the chemotherapy). In addition to comparing the anticancer activity and safety of the two therapies, a major aspect of the trial will be to determine if, and how well, PharmaCyte’s therapy can shrink inoperable tumors so that they may become operable.