On December 1, 2016 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported a data update on the first two cohorts of the company’s Phase I clinical study of CLR 131 in patients with relapsed or refractory multiple myeloma (Filing, 8-K, Cellectar Biosciences, DEC 1, 2016, View Source [SID1234516868]).

The clinical benefit rate for this study is 80 percent despite patients receiving an average of four prior treatments, including stem cell transplant and triple drug combinations. The patients in Cohort 1 received a single 12.5 mCi/m2 dose and patients in Cohort 2 received a single 18.75 mCi/m2 dose. At this time, Cohort 1 and Cohort 2 patients have demonstrated post treatment median survival of 11.9 months and 4.9 months, respectively. The median survival for all evaluable patients in both cohorts continues to increase and will be followed to determine overall survival benefit. Currently, the median overall survival (mOS) for each cohort is not yet evaluable. All evaluable patients in the clinical study experienced progression free survival (PFS). In Cohort 1, patients averaged 88.5 days of PFS. While patients in Cohort 2 have already achieved an average PFS of 127 days, the average PFS in Cohort 2 continues to increase as one of the four patients is still experiencing PFS. It is important to note that overall survival of 11.9 months and PFS of 127 days in this heavily pretreated patient population is better than or equivalent to that reported by several recently approved multiple myeloma drugs.

"The efficacy observed with CLR 131 at the 12.5 and 18.75 mCi/m2 single dose compares favorably to drugs recently approved for relapsed or refractory multiple myeloma. We believe that the 18.75 mCi/m2 dose could represent an acceptable single dose or multi-dose regimen for future studies," said Jim Caruso, president and CEO of Cellectar Biosciences. "Combined with its clean safety profile, we are optimistic regarding the potential of CLR 131 and look forward to seeing results from our recently initiated Cohort 3 at a single 25mCi/m2 dose."

An evaluation of adverse events between Cohort 1 and Cohort 2 reveal a similar profile. Patients in Cohort 1 experienced an average of 4.75 adverse events per patient while patients in Cohort 2 experienced an average of 4.25 events per patient. The median severity grade of the adverse events in both cohorts was 2.0 (mild to moderate), as graded by the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE).

In the multi-center, open label Phase I dose escalation study, CLR 131 was administered as a single dose, 30-minute intravenous infusion on Day 1 with 40 mg dexamethasone orally weekly for 12 weeks. The primary study objective is to characterize the safety and tolerability of CLR 131 with and without dexamethasone in patients with relapsed and/or refractory multiple myeloma. Secondary study objectives include establishment of a recommended Phase II dose, both with and without dexamethasone, as well as an assessment of therapeutic activity, including progression-free survival (PFS) and additional efficacy endpoints.

Dose-escalation in this study uses a minimally modified, standard 3+3 schema with dose-limiting toxicities (DLTs) assessed through day 85 post-infusion. Each cohort consisted of four evaluable patients (three men, one woman in Cohort 1 and two men, two women in Cohort 2). Patients in both cohorts received an average of 4 prior treatments. All patients received and were relapsed or refractory to proteasome inhibitors and immunomodulatory drugs prior to enrollment, and all patients had received triple combination therapy as a single line of therapy at least once. One patient in Cohort 1 and three in Cohort 2 received autologous stem cell transplantation and three Cohort 1 patients and one Cohort 2 patient each received the latest approved drugs for multiple myeloma prior to enrollment. Patient’s ages range between 55-76 (Cohort 1) and 55-85 (Cohort 2) and averages were essentially identical at 68 and 69 years of age, respectively.

The company is currently enrolling patients into the study’s third cohort at a single 25 mCi/m2 dose and plans to provide an additional data update in the first half of 2017.

About CLR 131

CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon pre-clinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About Phospholipid Drug Conjugates (PDCs)

Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in over 70 different xenograft models of cancer.

About Relapsed or Refractory Multiple Myeloma

Multiple myeloma is the second most common blood or hematologic cancer with approximately 30,000 new cases in the United States every year. It affects a specific type of blood cells known as plasma cells. Plasma cells are white blood cells that produce antibodies to help fight infections. While treatable for a time, multiple myeloma is incurable and almost all patients will relapse or the cancer will become resistant/refractory to current therapies.

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On December 1, 2016 ERYTECH Pharma (Paris:ERYP) (ADR:EYRYY) (Euronext Paris: ERYP), the French biopharmaceutical company developing ‘tumor starvation’ treatments for acute leukemia and other oncology indications with unmet medical needs, reported the presentation of promising preliminary data for the Company’s lead product candidate, eryaspase, also known as ERY-ASP or under the trade name GRASPA, at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 3-6, 2016 in San Diego, California (Press release, ERYtech Pharma, DEC 1, 2016, View Source;p=irol-newsArticle&ID=2226733 [SID1234516898]).

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The research was conducted at The University of Texas MD Anderson Cancer Center. Dr. Philip Lorenzi,

Co-Director of the Proteomics and Metabolomics Core Facility and lead author of the poster, will present a summary of the findings from a preclinical study which demonstrates that eryaspase, L-asparaginase encapsulated in red blood cells (RBC), has differential dual activity on its main targets, asparagine and glutamine, when compared to non-encapsulated native asparaginase (L-ASP), during a poster session.

Abstract #1266: Red Blood Cell-Encapsulation of L-Asparaginase Favorably Modulates Target Selectivity and Pharmacodynamics

Date:

Saturday, December 3, 2016
Time:
5:30 – 7:30 p.m. PST
Location:
Hall GH of the San Diego Convention Center
Poster Session:
101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and
Survival, Excluding Iron: Poster I

The anticancer effect of asparaginase products is attributed to the systemic degradation of asparagine, a critical amino acid for the growth and survival of cancer cells. Asparaginase is also known to have a glutaminase effect. The degradation of glutamine has been demonstrated to be associated with clinical toxicity. The study aimed to characterize the transport and degradation of the different amino acids between the plasma and the RBC cytoplasm in the presence of L-ASP or eryaspase. Using a new bioanalytical method, MD Anderson researchers analyzed several metabolites to study differential conversion of asparagine and glutamine. In the presence of eryaspase, asparagine was rapidly and extensively converted to aspartic acid inside the RBC, whereas eryaspase displayed significantly decreased glutaminase activity as compared to L-ASP. The approximately 3.5-fold increase in selectivity for asparagine over glutamine may explain the observed decrease in frequency of adverse events in clinical trials with eryaspase compared to L-ASP. Altered target selectivity is believed to be an additional beneficial property of the encapsulation in the RBC, on top of improved half-life and decreased immunogenicity. The results also provided further evidence of the ‘bioreactor’ mode of action of eryaspase, demonstrating that the enzymatic activity is essentially happening inside the RBC.

Dr. Lorenzi at The University of Texas MD Anderson Cancer Center, stated, "This work presents what we believe to be the first known solution to a long-standing challenge associated with measuring the pharmacodynamics of L-asparaginase products. Using a stable isotope-based correction method, we are now able to accurately determine the concentration of amino acids present at the time of sample collection. In this study, we used this method to identify reduced selectivity for glutamine as a plausible explanation for the improved toxicity profile of GRASPA over L-asparaginase that has been observed in prior clinical studies."

Dr. Iman El-Hariry, MD, PhD, Chief Medical Officer of ERYTECH, added, "We are pleased with these findings and believe that GRASPA has the potential to offer a new treatment option for cancer patients. This preclinical work demonstrates the unique mechanism of action of GRASPA and the important role of the RBC membrane in modulating the enzymatic activity of the encapsulated L-ASP on both asparagine and glutamine. The toxic side effects of L-ASP are believed to stem from its activity in degrading glutamine. These preclinical observations from MD Anderson researchers provide further support for our previously reported findings and demonstrate an improved therapeutic index of GRASPA in a clinical setting. We look forward to sharing our research to date with the global hematology community at the ASH (Free ASH Whitepaper) Annual Meeting."

On December 1, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data from an ongoing Phase 1/1b study of RXDX-105—Ignyta’s VEGFR-sparing, potent RET inhibitor—at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany, highlighting RXDX-105’s clinical activity in patients harboring RET molecular alterations, with five out of nine patients with RET fusion-positive cancers who were RET inhibitor-naïve achieving a RECIST response (1 complete response, 3 partial responses, and 1 unconfirmed partial response), for a preliminary objective response rate (ORR) of 56% (Abstract number 437, Poster number P116) (Press release, Ignyta, DEC 1, 2016, View Source [SID1234516870]).

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"This substantial update of our Phase 1/1b clinical data on RXDX-105 provides compelling evidence of its potent anti-tumor activity with promising durability and acceptable safety in patients with RET-fusion positive tumors," said Pratik Multani, M.D., Chief Medical Officer of Ignyta. "With approximately 500-fold higher potency against RET than VEGFR2 in vitro, RXDX-105 has the potential to address a critical unmet medical need in RET-positive patients for whom the clinical utility of multikinase inhibitors with both RET and VEGFR activity is constrained by safety liabilities and limited efficacy. We look forward to the continuation of the study to further explore the safety and efficacy of RXDX-105."

As of the November 2016, data cut-off, the findings showed:

Safety

A total of 91 patients with a range of solid tumors have been treated in the Phase 1/1b clinical trial, with 55 patients treated in the Phase 1 study and 36 patients treated in the Phase 1b study.

RXDX-105 continues to demonstrate a safety profile similar to what has been previously reported: across both studies, the most common treatment-related adverse events ( > 10% incidence) were rash (31%), fatigue (22%), diarrhea (20%), nausea (18%), hypophosphatemia (14%), vomiting (14%), muscle spasms (13%), and decreased appetite (10%);
The majority of treatment-related adverse events were Grade 1 or 2, and were reversible with dose modification;
The most common Grade 3 treatment-related adverse events ( > 5% incidence) were rash (9%), hypophosphatemia (7%), and ALT increase (6%);
One patient experienced a Grade 3 drug reaction with eosinophilia and systemic symptoms, in which the patient recovered with drug discontinuation. One patient experienced Grade 3 rash complicated by fatal alveolar hemorrhage. No other treatment-related Grade 4 or higher events were observed.
Toxicities commonly associated with VEGFR inhibition, such as hypertension, hypothyroidism, proteinuria, and neurotoxicity, were rarely observed ( < 5%).
Efficacy

Of the 36 patients treated in the Phase 1b study, 35 had RET or BRAF molecular alterations.

Nine RET inhibitor-naïve patients (n = 8 in the Phase 1b cohort; n = 1 in the Phase 1 cohort) with RET fusion-positive tumors were treated at a daily dose of 275 mg or 350 mg in the fed state, and were evaluable for response.

A preliminary ORR of 56% was observed in patients with RET fusion-positive solid tumors who were RET inhibitor-naïve (five out of nine treated patients had a RECIST response);
Of the five patients demonstrating a RECIST response, one patient with metastatic colorectal cancer (mCRC) achieved a complete response; three patients, all with non-small cell lung cancer (NSCLC), achieved a partial response; and one patient with NSCLC had an unconfirmed partial response;
Among the seven patients with RET fusion-positive NSCLC who were RET inhibitor-naïve, three achieved a partial response and one achieved an unconfirmed response (a second scan had not been obtained at the date of data cutoff), for a preliminary ORR of 57%;
Duration of response to RXDX-105 ranged from 2+ to 7+ months, with all responder patients currently continuing on treatment in active response; median duration of response, therefore, has not yet been determined;
Additionally, a previously disclosed Phase 1 patient with RET-mutated M918T medullary thyroid cancer had a confirmed partial response and continues on treatment after ten cycles.
These data confirm that RXDX-105 is active across a range of different histologies, with confirmed RECIST responses now observed in medullary thyroid cancer, NSCLC, and mCRC, and across a range of RET molecular alterations, including the M918T point mutation, and CCDC6-, EML4-, and PARD3-RET fusions.
Among the remaining patients treated in Phase 1b who were either RET fusion-positive and received prior RET inhibitor treatments (n = 4) or had BRAF molecular alterations (n = 23), durable disease control but no objective responses have been observed to date.

Based on the promising efficacy data observed thus far in patients with RET fusion-positive solid tumors who are RET inhibitor-naïve, this population will remain the primary focus of future development of RXDX-105. Enrollment in the Phase 1b study is ongoing to further explore the safety and efficacy of RXDX-105 in various molecular baskets at several doses.

On November 30, 2016 Dynavax Technologies Corporation (NASDAQ: DVAX) reported that it will present clinical data from a Phase 1/2 clinical trial evaluating its immuno-oncology product, SD-101, in patients with low-grade, B cell lymphoma (Press release, Dynavax Technologies, NOV 30, 2016, View Source [SID1234516841]). The poster presentation will be made at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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Abstract Name: SD-101, a Novel Class C CpG-Oligodeoxynucleotide Toll-like Receptor 9 Agonist, Given with Low Dose Radiation for Untreated Low Grade B-Cell Lymphoma: Interim Results of a Phase 1/2 Trial
Abstract Number: 2974
Date and Time: Sunday, December 4, 2016 from 6:00 p.m. EST to 8:00 p.m. EST
Session Name: 623. Mantle Cell, Follicular and Other Indolent B-Cell Lymphoma – Clinical Studies: Poster II
Location: San Diego Convention Center, Hall GH
Note: Abstract will also be published online on December 1, 2016, in the supplemental volume of the journal Blood
About SD-101

SD-101 is Dynavax’s proprietary, second-generation, Toll-like Receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

On November 30, 2016 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that a series of abstracts highlighting the latest clinical data on its in-house developed halichondrin class microtubule dynamics inhibitor eribulin mesylate (product name: Halaven, "eribulin") will be presented at the San Antonio Breast Cancer Symposium (SABCS2016) taking place in San Antonio, the United States, from December 6 to 10 (Press release, Eisai, NOV 30, 2016, View Source [SID1234516843]).

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Three abstract poster presentations (including outcome research data) are to be given at the meeting, with the main presentation featuring the results of an interim analysis of a Phase Ib/II trial (Study 218) of eribulin in combination with the immune checkpoint inhibitor pembrolizumab in patients with metastatic triple-negative breast cancer.

Eisai positions oncology as a key franchise area and is aiming to discover revolutionary new medicines with the potential to cure cancer. The company will continue to create innovation in the development of new drugs based on cutting-edge cancer research, and in doing so seeks to make further contributions to address the diversified needs of, and to increase the benefits provided to, patients and their families as well as to healthcare providers.

Major Eisai abstracts accepted for presentation at SABCS2016 include:
Product Abstract title and scheduled presentation date and time (local time)
Eribulin

Abstract P5-15-02 Phase Ib/II study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer
Poster Presentation | December 9 (Fri), 17:00-19:00
Eribulin

Abstract No: OT2-02-02 A randomized, open-label, multicenter, Phase Ib/II study of eribulin mesylate in combination with PEGylated recombinant human hyaluronidase (PEGPH20) versus eribulin mesylate alone in patients with human epidermal growth factor receptor 2 (HER2)-negative, high-hyaluronan metastatic breast cancer
Poster Presentation | December 8 (Thu), 17:00-19:00
Eribulin

Abstract No: P5-15-16 Utilization and outcomes of eribulin in triple-negative metastatic breast cancer:
real-world findings
Poster Presentation | December 9 (Fri), 17:00-19:00