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Cellectar Initiates Cohort 6 of Phase 1b Trial Evaluating CLR 131 in Relapsed/Refractory Multiple Myeloma

On December 4, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported the initiation of Cohort 6 of its ongoing Phase 1b trial evaluating CLR 131 for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) (Press release, Cellectar Biosciences, DEC 4, 2018, View Source [SID1234531899]). Cohort 6 will evaluate up to four patients with each receiving two doses of 18.75 mCi/m2 of CLR 131 administered one week apart. This fractionated dosing regimen will result in each patient being treated with a total of approximately 75.0 mCi of CLR 131, representing an increase in average total exposure of greater than 15% over Cohort 5.

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Cohort 5 also used a fractionated dosing regimen and results showed an ability to administer higher average drug exposure compared with previous cohorts that used bolus dosing. The results seen in Cohort 5 suggest the potential of fractionated dosing to reduce adverse events while improving efficacy. The independent Data Monitoring Committee (DMC) determined the Cohort 5 dose to be safe and well tolerated, and the DMC recommended advancement to the higher dose being used in Cohort 6.

"Cohort 6 builds upon the fractionated dosing we successfully employed with Cohort 5, and we look forward to the results from utilizing a higher drug concentration in this two-dose fractionated approach," said James Caruso, president and chief executive officer of Cellectar Biosciences. "Importantly," Caruso continued, "while cohort 5 showed fewer adverse events than cohort 4, total radiation exposure was greater."

Cohort 5 Results

Results from Cohort 5 indicated enhanced tolerability and safety compared with Cohort 4 despite an 18% increase in total average dose, from 55.29 mCi in Cohort 4 to 65.15 mCi in Cohort 5. Patients in Cohort 5 required less supportive care such as transfusions of platelets or packed red blood cells than seen in previous cohorts.

In addition to the improved safety profile demonstrated in Cohort 5, the company also monitored signals of efficacy. Despite Cohort 5 patients averaging five lines of prior systemic therapies, all patients experienced clinical benefit with two patients achieving minimal responses and two achieving stable disease. Furthermore, looking at surrogate markers, patients in Cohort 5 monitored by M-protein showed a nearly 50% further reduction in M-protein than seen in Cohort 4.

Based on these results and the DMC recommendation, Cellectar plans to modify the single-dose regimen of its ongoing Phase 2 trial of R/R hematologic malignancies to fractionated dosing.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated phospholipid ether-drug conjugate (PDC) therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in relapsed/refractory multiple myeloma (R/R MM) and a range of B-cell malignancies, and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2 as well as a fractionated dose of 15.625 mCi/m2 given twice over seven days in Cohort 5. All study doses and regimens have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company plans to initiate a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma as well as a second Phase 1 study in combination with external beam radiation for head and neck cancer.

About Phospholipid Drug Conjugates

Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized PDCs to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.

The EORTC Brain Tumor Group and Protagen AG announce their collaboration to investigate the immuno-competence of long-term Glioblastoma survivors

On December 4, 2018 The European Organisation for Research and Treatment of Cancer (EORTC) Brain Tumor Group and Protagen AG reported a collaboration to utilize Protagen’s Cancer Immunotherapy Array to identify autoantibody biomarkers that investigate the immunological profile and immuno-competence of long-term Glioblastoma survivors (Press release, EORTC, DEC 4, 2018, View Source [SID1234531897]).

Glioblastoma is the most common glial brain tumor with an annual incidence above 3 per 100,000 population. The overall prognosis of glioblastoma patients remains poor. According to population-based data, median overall survival (OS) is still in the range of only one year and long-term survival is rare. However, a minority of glioblastoma patients survive for more than 60 months and these individuals are referred to as long-term survivors. The US-based Brain Tumor Funders Collaborative (BTFC) is supporting a large international research program that aims at better understanding which individuals with glioblastoma will ultimately become long-term survivors.

Through the present new collaboration, Protagen and the EORTC Brain Tumor Group will utilize Protagen’s Cancer Immunotherapy Array to understand the immunological profile of such patients to learn how to predict such long-term survival and potentially define novel pathways for therapeutic intervention.

Prof. Michael Weller, Head of the Brain Tumor Center at University Hospital Zurich and Chairman of the EORTC Brain Tumor Group, stated: "In our network we have followed and investigated this group of long-term glioblastoma survivors for many years. The focus has been to understand the molecular profile of these patients and thus over the years we have gained a much better understanding. However, we really need to understand the immunological profile and the immuno-competence of these patients better. Thus, investigating these patients by utilizing Protagen’s Cancer Immunotherapy Array may enable us to define their immune-profile, so that we can assess their immuno-competence. This will help us, together with the data already collected, to potentially understand why these patients survive for so long and how this can be extrapolated to other patients suffering from glioblastoma."

Dr. Peter Schulz-Knappe, Protagen’s Chief Scientific Officer, commented: "Our unique Cancer Immunotherapy Array has already demonstrated its potential for the prediction of therapeutic response and immune-related adverse events in Immuno-Oncology. The extension into Glioblastoma with a specific view to studying long-term survivors with one of the deadliest tumors provides a great opportunity to apply the Array for the prediction of survival but also to learn more about potential novel pathways for therapeutic intervention. Thus, we believe that applying our technology will result in a better understanding of the immunological profile of these long-term survivors which will benefit all patients suffering from Glioblastoma. We feel privileged that the EORTC Brain Tumor Group shares this vision, and are excited about the collaboration."

Cofactor Genomics to Provide Solid Tumor Immune Profiling for Genocea Biosciences

On December 4, 2018 Cofactor Genomics, a clinical RNA sequencing and translational assay developer, reported a pilot study to evaluate use of Cofactor’s ImmunoPrismTM assay in Genocea Biosciences’ Phase 1/2a clinical trial testing the safety and efficacy of its lead personalized cancer vaccine candidate, GEN-009, in adult cancer patients with a variety of solid tumors (Press release, Cofactor Genomics, DEC 4, 2018, View Source [SID1234531892]).

The pilot study is designed to enable Genocea to comprehensively characterize the immune responses that patients enrolled in the clinical trial generate in response to vaccination. The RNA-based assay developed by Cofactor should enable Genocea to compare the immune cell composition for 8 major immune types within and between patients, including expression reporting for key immune escape genes.

"We are working to develop truly effective personalized neoantigen vaccines with which to treat cancer patients. Through exploration of advanced technologies like Cofactor’s ImmunoPrism assay, we aim to better understand the intratumoral immune responses we are eliciting in response to our vaccine," said Jessica Baker Flechtner, Ph.D., Chief Scientific Officer at Genocea.

"Pilot studies such as this one, where our technology is implemented in the field to empower drug developers to find the most robust markers of therapeutic success, are extremely important in validating our cutting-edge technology," noted David Messina, Chief Operating Officer at Cofactor Genomics. "Demonstrating the utility of a new approach to immune profiling is best accomplished with partners like Genocea, who are eager to gain access to the most innovative and advanced assays."

Cofactor Genomics recently announced the release of their ImmunoPrism Immune Profiling Kit, which enables access to their proprietary molecular and machine-learning informatics for RNA analysis of the tumor microenvironment. The ImmunoPrism kit offers laboratories the ability to validate the assay, as Cofactor has done through their CAP-accredited laboratory.

Cofactor will present the results of this clinical validation work during an upcoming webinar titled, "Clinical Validation of a Multidimensional Pan-Cancer Immune Assay" on Thursday, December 13 at 11 AM EST: View Source

Gamida Cell Announces Publication of Phase 1/2 Clinical Data of NiCord® in the Journal of Clinical Oncology

On December 4, 2018 Gamida Cell Ltd. (Nasdaq: GMDA), a leading cellular and immune therapeutics company, reported the publication of data from the previously reported, multi-center Phase 1/2 clinical study evaluating the safety and efficacy of NiCord as a stand-alone, hematopoietic stem cell (bone marrow) transplant in the Journal of Clinical Oncology1,2 (Press release, Gamida Cell, DEC 4, 2018, View Source [SID1234531889]). NiCord is an investigational product candidate in Phase 3 development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies, or blood cancers.

Results from the Phase 1/2 study showed that patients transplanted with NiCord had rapid and durable engraftment of neutrophils and platelets, as well as prompt immune reconstitution. The median time to neutrophil recovery was shortened by nearly 50 percent for patients who received NiCord compared to a retrospective cohort of patients who received standard umbilical cord blood. NiCord also demonstrated an acceptable safety profile for patients undergoing bone marrow transplant.

"In this study, patients who received NiCord had a clinically meaningful reduction in their time to neutrophil and platelet recovery compared to a retrospective cohort of patients who received a standard umbilical cord blood transplant. The neutrophil recovery observed with NiCord also resulted in fewer days spent in the hospital compared to the comparator cohort," said Mitchell Horwitz, M.D., principal investigator and professor of medicine at the Duke Cancer Institute. "These data suggest a potential step toward making stem cell transplantation safer and more accessible to patients with lethal blood cancers."

Despite the curative potential of bone marrow transplants, it is estimated that more than 40 percent of eligible patients do not receive one for various reasons, including finding a matched donor.3 While umbilical cord blood provides a source of stem cells for patients who do not have a matched related donor, it provides a smaller number of stem cells, which can delay engraftment and put patients at a greater risk for prolonged hospitalizations and life-threatening infections. NiCord is designed to address these limitations by offering a therapeutic dose of expanded cells while preserving the functional characteristics of stem cells.

NiCord Phase 1/2 Study Design and Results
The publication, "Phase I/II study of stem cell transplantation using a single cord blood unit expanded ex vivo with nicotinamide," described results from the completed multicenter, Phase 1/2 clinical trial of NiCord in 36 patients with high-risk hematologic malignancies and no readily available matched sibling or matched unrelated adult donor. The key primary endpoint was the cumulative incidence of neutrophil engraftment at 42 days. Additionally, the NiCord patient cohort was compared to a retrospective cohort of patients who received standard cord blood transplant using data from the Center for International Blood and Marrow Transplant Research (CIBMTR).

Key findings included the following:

Patients transplanted with NiCord had rapid and durable engraftment of neutrophils and platelets, as well as prompt immune reconstitution. The age-adjusted cumulative incidence of neutrophil engraftment at 42 days following transplantation was 94 percent for NiCord recipients compared to 85 percent for the CIBMTR cohort.
Among patients who engrafted, the median time to neutrophil recovery was 11.5 days (95% CI: 9-14 days) for NiCord recipients compared to 21 days (95% CI: 20-23 days) for the CIBMTR cohort (p<0.001).
For patients achieving platelet recovery, the median time to platelet recovery was 34 days (95% CI:32-42 days) and 46 days (95% CI:42-50 days) for the NiCord and CIBMTR cohorts, respectively (p<0.001).
NiCord demonstrated an acceptable safety profile, with hypertension reported as the most common adverse event attributable to NiCord infusion, and moderate to severe chronic graft vs. host disease reported in 9.8 percent of patients at one year following transplantation.
Primary hospital discharge occurred at a median of 20 days following transplantation. NiCord recipients spent a median of 73 days alive and out of hospital during the first 100 days following UCB transplantation.
"These data demonstrate the potential of NiCord to give patients with high-risk blood cancers an opportunity for a cure, particularly patients who would otherwise not be able to receive a bone marrow transplant using a matched donor source," stated Ronit Simantov, M.D., chief medical officer at Gamida Cell. "We are actively enrolling patients in our Phase 3 study, which is designed to confirm the potential of NiCord to be an effective transplantation solution. We look forward to completing patient enrollment expected in the second half of 2019."

About NiCord
NiCord, the company’s lead clinical program, is under development as a universal bone marrow transplant solution for patients with high-risk hematologic malignancies. NiCord has been granted breakthrough status by the U.S. Food and Drug Administration, making it the first bone marrow transplant alternative to receive this designation. It has also received U.S. and EU orphan drug designation. A Phase 3 study evaluating NiCord in patients with leukemia and lymphoma is ongoing in the United States, Europe and Asia.4 For more information on NiCord clinical trials, please visit www.clinicaltrials.gov.

AVEO Oncology Announces Extension of Debt Facility Interest Only Period

On December 4, 2018 AVEO Oncology (NASDAQ:AVEO) reported a six-month extension to the interest only period under its existing amended and restated loan and security agreement with Hercules Capital, Inc. (Hercules) (Press release, AVEO, DEC 4, 2018, View Source [SID1234531888]). The extension was granted as a result of achieving certain predefined requirements under the agreement, including successfully meeting the primary endpoint of the Company’s Phase 3 TIVO-3 study of tivozanib in refractory advanced or metastatic renal cell carcinoma (RCC), by demonstrating a significant improvement in progression free survival.

The Company will begin making principal payments on the $20.0 million facility starting on August 1, 2019. AVEO believes that its available cash, cash equivalents, and marketable securities, together with the extension of the interest only period under the Hercules loan agreement, which results in deferment of principal payments, will allow it to fund planned operations into Q3 2019. This estimate assumes no receipt of additional milestones from AVEO’s partners, no additional funding from new partnership agreements, no additional equity or debt financings, and no sales of equity through the exercise of outstanding warrants issued in connection with the 2016 private placement or outstanding warrants issued in connection with the settlement of the securities class action litigation.

"Extension of our cash runway takes us through several key anticipated milestones, with the presentation of our TIVO-3 data, including a planned update to the preliminary OS analysis which will contain additional patient data recovered in the ongoing OS sweep, and potential submission of a New Drug Application with the FDA for tivozanib in RCC. Both milestones are expected in the first half of 2019," said Michael Bailey, president and chief executive officer. "We also look forward to making important progress within this period on our immunotherapy combination strategy, the third pillar of our tivozanib strategy."