On October 9, 2014 CytRx Corporation reported the initiation of enrollment in an open-label Phase 1b clinical trial designed to investigate the preliminary safety and activity of aldoxorubicin plus gemcitabine in subjects with metastatic solid tumors (Press release CytRx, OCT 9, 2014, View Source [SID:1234500810]). Aldoxorubicin is CytRx’s modified version of the widely-used chemotherapeutic agent, doxorubicin.

The Phase 1b clinical trial will be conducted at the Virginia G. Piper Cancer Center in Scottsdale, AZ, the Samuel Oschin Cancer Center at Cedars Sinai Medical Center, Los Angeles, CA, and the Sarcoma Oncology Center in Santa Monica, CA. The clinical trial is expected to enroll up to 30 male and female patients between the ages of 15 and 80 with advanced, unresectable, metastatic solid tumors that have either relapsed or were refractory to treatment with at least one prior chemotherapy or immunotherapy regimen and for which no standard approved therapy exists. The Company expects to complete enrollment by the third quarter of 2015.

“Initiation of clinical development of aldoxorubicin in combination with gemcitabine for the treatment of metastatic solid tumors represents a potentially significant expansion of our aldoxorubicin franchise in cancer treatment,” said CytRx CEO Steven A. Kriegsman. “The start of this combination chemotherapy with aldoxorubicin will allow our testing to move into a variety of new tumors such as pancreatic and ovarian cancers as well as hematological malignancies.”

For this clinical trial, aldoxorubicin will be administered at escalating doses by intravenous infusion (IVI) on Day 1 every 21 days plus 900 mg/m2 gemcitabine on Days 1 and 8 every 21 days until disease progression, unacceptable toxicity or the patient withdraws consent. The primary objective of the trial is to determine the preliminary safety of administration of aldoxorubicin in combination with gemcitabine in subjects with metastatic solid tumors as measured by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiograms (ECHO) or multiple-gated acquisition (MUGA) scans, electrocardiogram (ECG) results, and weight. The secondary objective of the trial is to evaluate the activity of aldoxorubicin in combination with gemcitabine in this population, assessed by overall response rate (ORR), progression-free survival (PFS), and PFS at 4 and 6 months.

Aldoxorubicin is also currently being studied in a pivotal global Phase 3 clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with STS under a Special Protocol Assessment with the FDA. CytRx is also evaluating aldoxorubicin in two Phase 2 clinical trials, one in patients with late-stage glioblastoma (GBM) and the other in HIV-related Kaposi’s sarcoma, a global Phase 2b clinical trial in patients with relapsed small cell lung cancer, and in a Phase 1b trial in combination with ifosfamide in patients with soft tissue sarcoma.

On October 9, 2014 Amgen reported that the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for the investigational bispecific T cell engager (BiTE) antibody construct, blinatumomab (Press release Amgen, OCT 9, 2014, View Source [SID:1234500807]). The BLA is for the treatment of adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer of the blood and bone marrow. As part of the acceptance, the FDA granted blinatumomab priority review with a Prescription Drug User Fee Act (PDUFA) action date of May 19, 2015.

A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) via the centralized procedure for approval to market blinatumomab for the treatment of adults with Ph- relapsed/refractory B-precursor ALL.

The submissions include data from a Phase 2 trial of adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab, which met its primary endpoint.

“The FDA’s acceptance of our BLA submission and designation of priority review for blinatumomab underscores the need to provide new treatment approaches for adult patients with relapsed or refractory ALL, and we are encouraged by the Agency’s expedited review,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “Blinatumomab has the potential to make a significant impact for these patients, and this milestone, along with other ongoing filings around the world, represents the potential of BiTE technology in cancers that are challenging to treat.”

BiTE antibody constructs represent an innovative immunotherapy approach that helps the body’s immune system target cancer cells. Blinatumomab, the first of the investigational BiTE antibody constructs, has received orphan drug designation from the EMA and FDA, and breakthrough therapy and priority review designation from the FDA for the treatment of ALL.

According to the FDA, priority review designation is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. A priority review designation will set a goal date for taking action on an application within six months of receipt.

In the U.S., more than 6,000 cases of ALL will be diagnosed in 2014, and in the European Union, it is estimated that more than 7,000 cases of ALL are diagnosed each year. In adult patients with relapsed or refractory ALL, median overall survival is just three to five months.