CytRx, a biopharmaceutical R&D company specializing in oncology, has announced an interim analysis from its two ongoing phase Ib aldoxorubicin combination studies pairing aldoxorubicin with either gemcitabine or ifosfamide. Both studies combine standard doses of gemcitabine or ifosfamide with escalating doses of aldoxorubicin. The combinations appear to be well-tolerated, and even at the lowest dose level of aldoxorubicin (170mg/m2), impressive tumor responses have been observed so far in patients with bone cancer (osteosarcoma) and a variety of soft tissue sarcomas. As such, aldoxorubicin has the potential when used in combination with other cancer agents to become an important new weapon against chemotherapy resistant cancers.

"I am very excited so far with both the tolerability and activity of these combinations," said Dr. Sant Chawla, Principal Investigator and director of the Sarcoma Oncology Center, Santa Monica, Calif. "Our first patient with osteosarcoma treated with ifosfamide plus aldoxorubicin had a PET-demonstrated complete tumor response after only five cycles of the combination that has persisted for over six months. Several patients administered the gemcitabine plus aldoxorubicin combination showed tumor shrinkage after only two cycles of treatment, and a patient with advanced cartilage/bone cancer, a rare and deadly cancer, was able to stop all pain medication except Advil and returned to work full time. These results support the further study of these combinations in larger outcome clinical trials."

The first study is an open-label, phase Ib clinical trial investigating the preliminary safety and activity of ascending doses of aldoxorubicin plus ifosfamide/mesna for the first-line treatment of patients with locally advanced, unresectable and/or metastatic sarcomas, including bone cancer.

Interim results from seven evaluable patients show that the combination of aldoxorubicin plus ifosfamide/mesna was well tolerated. One bone cancer patient achieved a complete tumor response following five treatment cycles. The company expects to complete dose escalation in this trial in the second half of 2015, and to begin adding sarcoma patients at the maximum well-tolerated dose combination.

The second trial is an open-label, phase Ib clinical trial investigating the preliminary safety and activity of ascending doses of aldoxorubicin plus gemcitabine in patients with advanced, unresectable, metastatic solid tumors that have either relapsed or were refractory to treatment following at least one prior chemotherapy or immunotherapy regimen, and for which no standard approved therapy exists.

Interim results from seven patients show that the combination of aldoxorubicin plus gemcitabine was well tolerated. Tumor shrinkage was observed in three of seven patients following two treatment cycles. One patient with advanced dedifferentiated chondrosarcoma (cartilage/bone cancer), chronic severe pain and inability to function normally demonstrated meaningful quality of life improvements, including stopping prescription narcotic pain medications and returning to full-time work. The company expects to complete dose escalation in this trial in the second half of 2015, and to begin adding patients with either relapsed pancreatic or ovarian cancer at the maximum well-tolerated dose combination.

"We believe that aldoxorubicin has the potential to be combined with other anti-cancer agents in order to improve patient outcomes for many types of cancer," said Steven A. Kriegsman, chairman and CEO of CytRx. "These results, which include excellent tolerability and compelling initial signs of activity, even at the lowest dose of aldoxorubicin, provide an opportunity to expand the aldoxorubicin development pipeline and explore additional indications. For aldoxorubicin plus gemcitabine, we are exploring further development of this combination as a treatment for patients with advanced pancreatic or ovarian cancers that have relapsed, or not yet responded, following initial courses of chemotherapy. We are encouraged by these initial results and look forward to providing updates on these studies as they reach completion."

In the 30-subject, multisite, phase Ib trial, aldoxorubicin is being administered at escalating doses by intravenous infusion (IVI) on day one every 28 days, and 1gm/m2/day of ifosfamide and an equivalent dose of mesna will be administered via continuous infusion with a portable at-home pump for up to 14 days every 28 days starting on day one of each cycle, 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 ifosfamide in subjects with metastatic, locally advanced, or unresectable STS 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 ifosfamide/mesna in this population, assessed by overall response rate (ORR), progression-free survival (PFS) and PFS at four and six months.

The 30-subject, multisite, phase Ib trial, aldoxorubicin is being administered at escalating doses by intravenous infusion (IVI) on day one every 21 days plus 900mg/m2 gemcitabine on days one and eight 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 four and six months.