ROCKVILLE, Md.—Rexahn Pharmaceuticals Inc. announced recently that it has identified a maximum tolerated dose and completed stage 1 of a dose-escalation Phase 2a clinical trial of Archexin in combination with everolimus, a widely used chemotherapy drug, in patients with metastatic renal cell carcinoma (RCC). In addition, Rexahn also announced that it has commenced enrollment in stage 2 of the Phase 2a Archexin clinical trial to evaluate safety and efficacy of the combination.
“Data from the first phase (stage 1) of the Archexin clinical trial have yielded exciting preliminary clinical findings suggesting that Archexin, in combination with everolimus, showed evidence of a potential dose- and time-dependent clinical benefit in patients with advanced, metastatic kidney cancer,” said Dr. Ely Benaim, chief medical officer for Rexahn. “The data from stage 1, which were recently presented at the American Society for Clinical Oncology Genitourinary Cancers Symposium, show three patients who have experienced stable disease for 383, 191 and 122 days, respectively, and two patients who experienced a tumor burden reduction of 16 percent and 36 percent, respectively, as of Jan. 6, 2016.”
The results indicated that at the dose levels tested to date, Archexin appeared to be safe and well tolerated. The most commonly reported adverse events in the patients taking both Archexin and everolimus included thrombocytopenia (a low blood platelet count), mouth ulcerations, decreased weight, facial edema and hyponatremia (low blood sodium levels). To date, none of these adverse events have been dose-limiting.
Benaim continued, “While preliminary, we are particularly excited about the results from this study, as these are heavily pretreated patients who have not previously responded to other cancer therapies. Consequently, we are pleased to begin enrollment in stage 2 of the Phase 2a clinical trial to further evaluate the potential anticancer effects of Archexin in patients with advanced, metastatic kidney cancer.”
Benaim added that they are encouraged by enrollment so far, which Rexahn expects to be completed by the end of the year.
“We are excited to present interim data from the ongoing Phase 2a clinical trial showing that Archexin, in combination with everolimus (Afinitor), appears to be safe and well tolerated at the doses tested to date. We have also noted early evidence of clinical activity at low doses in patients with metastatic kidney cancer,” commented Peter D. Suzdak, Rexahn’s CEO. “We look forward to completing the randomized, open-label, 2-arm dose expansion study of Archexin in combination with everolimus versus everolimus alone in order to further evaluate Archexin in metastatic renal cell carcinoma.”
In stage 1, escalating doses of Archexin of 125, 200 and 250 mg/m2/day were administered by continuous intravenous infusion for 14 days followed by one week of rest. Patient assessments include safety, pharmacokinetics, laboratory and physical exams.
Stage 2 of the Phase 2a clinical study is a randomized, open-label, two-arm dose expansion study of Archexin in combination with everolimus, versus everolimus alone, to determine safety and efficacy of the combination. The trial is anticipated to enroll up to 30 RCC patients who will be randomized to receive either Archexin in combination with everolimus, or everolimus alone, in a ratio of 2:1. The maximum tolerated dose of 250 mg/m2/day of Archexin—identified in stage 1—will be administered along with 10 mg of everolimus versus 10 mg everolimus alone.
The primary endpoint of stage 2 is the percentage of progression-free patients following eight cycles of therapy, Benaim notes. Patients undergo CT or MRI scans for the assessment of tumor progression after every two cycles of therapy. Secondary endpoints include pharmacokinetic profile, incidence of adverse events, changes in clinical laboratory tests and vital signs over time, tumor response, duration of response, time to response and response rate. Exploratory endpoints include blood levels of Akt pathway biomarkers, tumor apoptosis biomarkers or other relevant biomarkers.
Archexin is a unique antisense drug candidate that specifically inhibits the cancer cell signaling protein Akt-1. Archexin is the only specific inhibitor of Akt-1 in clinical development. The activated form of Akt-1, which is involved in cancer cell growth, survival, angiogenesis and drug resistance, has been shown to be present or elevated in more than 12 different human cancer cell lines, including pancreatic and renal cell carcinoma. By inhibiting Akt-1, Archexin has been shown to both inhibit the growth of renal cell carcinoma cell lines and exhibit a longer survival benefit in the human renal cell carcinoma animal xenograft model.
Rexahn has received U.S. Food and Drug Administration Orphan Drug designation for Archexin for metastatic RCC as well as four other cancers. Metastatic RCC represents an attractive market opportunity with an estimated annual incidence of 90,000 patients worldwide. Currently, metastatic RCC patients receiving standard-of-care treatment have a poor prognosis, with an overall survival of less than two years.