On October 24, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB), an oncology-focused, clinical stage biotechnology company (the “company”), reported the design of the multiple dose fifth cohort of its Phase I dose escalation safety trial of lead PDC compound, CLR 131, in relapse or refractory multiple myeloma (Press release, Cellectar Biosciences, OCT 24, 2017, View Source [SID1234521126]). Cohort 5 will utilize two 15.625 mCI/m2 doses given one week apart with the total combined dose equaling 31.25 mCi/m2, the same total dose provided to patients that resulted in a partial response in Cohort 4. In previous cohorts, CLR 131 was given in a single infusion.

In September, the trial’s Data Monitoring Committee (DMC) determined that the fourth cohort single dose of 31.25 mCi/m2 was safe and tolerated. In addition, the DMC determined that the use of a split, or repeat dose might be advantageous. Given internal company data and recently announced results of preclinical studies in which 2 doses of CLR 131 demonstrated a statistically significant improvement in survival benefits and reduction of tumor volume in multiple mouse models (April 27, 2017), the company has enhanced the study’s protocol such that subsequent cohorts will include repeat dosing.

“Given the encouraging results we’ve observed to date in previous cohorts, we hope to see similar, or perhaps even improved safety results in this arm of the trial,” said Natalie Callander, M.D., professor of medicine, director, University of Wisconsin Carbone Cancer Center Myeloma Clinical Program, and the study’s lead investigator. “Previous participants have asked us if it was possible to receive additional doses, as this therapy has been so well tolerated.”

Patients participating in the fifth cohort will receive a total of two doses of CLR 131 as 30-minute infusions on their first and seventh days. They will then be evaluated over the course of 85 days to determine the safety and efficacy of the treatment as per the study protocol. During the previous cohort, one of three evaluable patients experienced a partial response to treatment with CLR 131, while the other two achieved stable disease. All Cohort 4 patients had heavily pretreated relapsed or refractory multiple myeloma (greater than five prior lines) and high degree of tumor burden upon entry into the trial, and the company expects to recruit similar trial subjects for Cohort 5. Despite the challenging patient population enrolled to date, 89 percent of all Phase 1 patients achieved a clinical benefit response.

“This fifth cohort represents an important opportunity to better understand the clinical utility of a split dose regimen and to further explore the safety and efficacy of CLR 131. Utilizing two doses provides an opportunity to increase the total amount of drug delivered to the patients which could result in an improvement in efficacy while maintaining similar or better safety profile,” said Jim Caruso, president and CEO of Cellectar Biosciences. “Clinical assessment, along with the improved benefits demonstrated by two doses in preclinical studies, suggest to us that the protocol changes should enhance our chances to see improved patient outcomes in this and future study arms.”

About CLR 131

CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated as a single-dose treatment in a Phase 1 clinical trial in patients with relapsed or refractory (R/R) multiple myeloma (MM) as well as in a Phase 2 clinical trial for R/R MM and select R/R lymphomas with either a one- or two-dose treatment. CLR 131 represents a novel approach to treating hematological diseases and based upon preclinical and interim Phase 1 study data may provide patients with therapeutic benefits including, overall survival, an improvement in progression-free survival, 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 designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate the discovery and development of improved targeted novel therapeutic compounds. 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 more than 80 different xenograft models of cancer.

On October 24, 2017 Moleculin Biotech, Inc., (NASDAQ: MBRX) (“Moleculin” or the “Company”), a clinical stage pharmaceutical company focused on the development of anti-cancer drug candidates, some of which are based on license agreements with The University of Texas System on behalf of the M.D. Anderson Cancer Center, reported that has submitted its request for Clinical Trial Authorization (“CTA”) in Poland which, if allowed, will enable a clinical trial to study Annamycin for the treatment of relapsed or refractory acute myeloid leukemia (“AML”) in Poland (Press release, Moleculin, OCT 24, 2017, View Source [SID1234521124]). This will be in addition to the previously announced allowance of its Investigative New Drug filing with the Food & Drug Administration in the US.

“Consistent with our prior guidance, we have now taken the final step required to expand our Annamycin clinical trial to Poland,” commented Walter Klemp, Chairman and CEO of Moleculin. “Unlike the US, the process for beginning a clinical trial in Poland requires a hospital contract before a request for CTA can be made. We recently announced the required hospital contract and this announcement now marks the formal request for Polish approval.”
Mr. Klemp continued: “The CTA request process in Poland normally takes 60 days, so we hope to be enrolling patients there near year-end. Increasing the breadth of clinical trial sites beyond the US will give Moleculin access to more potential patients, and, hopefully, speed the Phase IIa portion of the trial.”

On October 24, 2017 Molecular Templates, Inc., (Nasdaq:MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), reported the dosing of the first patient in a Phase 1 expansion study of MT-3724, a first-generation ETB that targets the CD20 cell surface antigen present in a variety of lymphomas and leukemias (Press release, Molecular Templates, OCT 24, 2017, View Source [SID1234521123]). Strong evidence of anti-tumor activity in heavily pre-treated patients has been observed in Part 1 of the study.

“MT-3724 has shown activity in heavily pre-treated DLBCL patients with a median of greater than four prior therapies in the dose escalation portion of this study,” said Eric E. Poma, Ph.D., Chief Executive and Chief Scientific Officer of Molecular Templates. “We are pleased to begin dosing patients in the expansion cohort, which is designed to further characterize the efficacy and response rates in these difficult to treat patients.”
The Phase 1 study is a two-part study in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma or relapsed/refractory B-cell CLL. In Part 1, patients were treated with MT-3724 given as intravenous (IV) infusions at doses ranging from 5 mcg/kg up to 100 mcg/kg. The primary outcome measures are safety and tolerability, while secondary endpoints are pharmacokinetics (PK), pharmacodynamics (PD) and tumor response. The MTD was identified as 75 mcg/kg and this was supported by a dose-dependent clearance of CD20+ peripheral B cells, which is an acknowledged surrogate marker of efficacy.

Establishment of the MTD has triggered initiation of Part 2 of the study, in which relapsed or refractory DLBCL patients without high serum levels of Rituxan will be treated with MT-3724 as a monotherapy at the MTD dose. The study has been designed to enroll up to 40 patients in total.

Part 2 of the study is being conducted at multiple centers across the United States including Memorial Sloan-Kettering Cancer Center in New York City, the MD Anderson Cancer Center in Houston, Texas, and the University of Arizona in Tucson, Arizona with data expected in the first half of 2018. Molecular Templates anticipates initiating a phase II monotherapy study in relapsed and refractory DLBCL patients in 2018 that could be pivotal in nature. The first patient was dosed at the University of Arizona. Additional information on the study, including inclusion/exclusion criteria, can be found at www.clinicaltrials.gov (NCT Identifier: NCT02715843).

About MT-3724
MT-3724, Molecular Templates’ lead drug candidate, is an immunotoxin that targets the CD20 cell surface antigen present in a variety of lymphomas and leukemias. CD20 is a non-internalizing receptor and MT-3724 is the first immunotoxin to induce internalization and destruction of CD20 positive cells to enter the clinic. MT-3724 is currently being investigated in a Phase 1 clinical trial in heavily pre-treated Diffuse Large B-cell Lymphoma (DLBCL) patients. More information is available at clinicaltrials.gov.

On October 24, 2017 Varian (NYSE: VAR) reported five patients with brain cancer became the first patients in the US to be treated using the company’s HyperArc High Definition Radiotherapy (HDRT), a new type of radiosurgery treatment, at the University of Alabama at Birmingham Comprehensive Cancer Center (Press release, InfiMed, OCT 24, 2017, View Source [SID1234521122]). HyperArc is designed to automate and simplify sophisticated treatments such as stereotactic radiosurgery (SRS) and make them available to more cancer patients around the world.

“We have been doing preclinical and clinical development of single isocenter radiosurgery for a decade,” said John Fiveash, M.D., professor and vice chair for academic programs in the UAB Department of Radiation Oncology. “Over the last five years, our radiosurgery plan quality has improved to equal or exceed our Gamma Knife. Physicians and patients preferred the frameless and highly efficient delivery on our TrueBeam and Edge systems and our Gamma Knife was decommissioned June 2017. HyperArc planning automates much of the radiosurgery treatment planning strategies that we have implemented at UAB and could enable more clinics to perform higher quality radiosurgery for more patients.”

“Working closely with leading institutions like UAB played an important role in the development of HyperArc,” said Kolleen Kennedy, president of Varian’s Oncology Systems business. “We value their continued contributions to the advancement of cancer care and we are excited that HyperArc treatments have now begun in the US.”

HyperArc capitalizes on the unique capabilities of Varian’s TrueBeam and EDGE treatment systems. HyperArc treatments allow clinicians the ability to deliver more compact radiation doses that closely conform to the size, shape, and location of tumors while sparing more surrounding healthy tissue. These advanced treatments can be delivered in a conventional treatment time slot. The treatment planning for HyperArc is supported by Varian’s Eclipse treatment planning software.

For more information on HyperArc, visit www.varian.com/hyperarc

On October 24, 2017 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported the initiation of a multi-arm clinical trial evaluating PEGPH20, Halozyme’s investigational new drug, in combination with atezolizumab (TECENTRIQ), an anti-PDL1 cancer immunotherapy from Genentech, a member of the Roche Group (Press release, Halozyme, OCT 24, 2017, View Source [SID1234521121]). The combination will be tested in patients with previously treated, locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer.

The study is sponsored by and funded by Genentech as part of a clinical collaboration agreement announced last year to evaluate PEGPH20 and atezolizumab in up to eight tumor types. Genentech initiated the first study in July to evaluate the combination in patients with previously treated metastatic pancreatic ductal adenocarcinoma.

The gastric cancer study is a Phase 1b/2, open-label, multicenter, randomized clinical trial designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations compared with the standard chemotherapy regimens. It will enroll an all-comer population regardless of hyaluronan (HA) level. The overall analysis plan includes a retrospective analysis of the HA-high population identified using the Ventana HA companion diagnostic assay.

HA is a glycosaminoglycan, or chain of natural sugars in the body that can accumulate around cancer cells creating high pressure in a tumor, constricting blood flow and thereby reducing access of chemotherapy and immunotherapeutic agents. PEGPH20 is an enzyme that temporarily degrades HA, reducing tumor pressure and potentially increasing blood flow, allowing greater access for chemotherapies and immunotherapies to treat the tumor.

The study will be conducted in the U.S., as well as countries outside the U.S.

The collaboration between Halozyme and Genentech includes testing the experimental combination in MORPHEUS, Roche’s Novel Cancer Immunotherapy Development Platform. MORPHEUS is a Phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently.

“PEGPH20 is currently under evaluation in six indications with potential across a range of difficult to treat solid tumors,” said Dr. Helen Torley, president and chief executive officer. “Our hope is to advance new treatment options for patients with each ongoing study.”

About PEGPH20 (pegvorhyaluronidase alfa)
PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the potential systemic treatment of tumors that accumulate hyaluronan. PEGPH20 is an enzyme that temporarily degrades HA, a dense component of the tumor microenvironment that can accumulate in higher concentrations around certain cancer cells, potentially constricting blood vessels and impeding the access of other therapies.

FDA granted orphan drug designation to PEGPH20 for treatment of pancreas cancer and fast track designation for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreas cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreas cancer.