OGX-427 Clinical Trial Results
OGX-427 has been evaluated in a phase 1 trial in patients with bladder, breast, prostate, ovarian, or NSCLC who have failed potentially curative treatments or for which a curative treatment does not exist. Final results of this phase 1 trial were presented during an oral presentation at the 2010 American Society of Clinical Oncology Annual Meeting. Click here to see the abstract.
The phase 1 trial evaluated 36 patients treated with OGX-427 as a single agent and 12 patients with OGX-427 in combination with docetaxel who had failed up to six prior chemotherapy treatments. OGX-427 as a single agent administered weekly was evaluated at doses from 200 mg up to 1000 mg in five cohorts of approximately six patients in each cohort. Two further cohorts tested OGX-427 at the 800 and 1000 mg doses combined with docetaxel. Patients could receive up to ten 21-day cycles.
OGX-427 was well tolerated both as a monotherapy and in combination with docetaxel. Most adverse events were mild (grade 1 or 2) and mainly occurred during the three “loading doses” given over nine days prior to weekly dosing. The majority of adverse events potentially related to OGX-427 consisted of grade 1 or 2 fever, chills, itching, or flushing (associated with the infusion of OGX-427) and fatigue. Despite evaluating OGX-427 at very high doses, a maximum tolerated dose for OGX-427 was not reached in this trial.
Of particular interest was the decrease at all doses and in all diseases evaluated in the trial for both total circulating tumor cells (CTCs), and CTCs which were positive for Hsp27, Hsp27(+) CTCs. Recent studies have shown that the presence of CTCs in peripheral blood may be of prognostic significance for patients with solid tumors and patients with values of ≤ 5 CTCs are generally considered to have a more favorable prognosis.
When OGX-427 was used as monotherapy, 3 of 17 evaluable patients had a decrease in measurable disease of 20% or greater. In this heavily pretreated patient population, 2 of 4 patients with ovarian cancer had a decrease of 25% or greater in CA-125 (an ovarian tumor marker) and 3 of 15 patients with prostate cancer had a decrease of 30% or greater in PSA (a prostate tumor marker). Hsp27 (+) CTC decreases were noted in 89% of evaluable patients and were observed at all dose levels and in all diseases evaluated. In 9 of 26 (31%) patients with ≥ 5 Hsp27 (+) CTCs at baseline, Hsp27 (+) CTCs had decreased to ≤ 5 CTCs. In addition, serum Hsp27 protein levels were decreased by 30% or greater over a period of at least six weeks in approximately 25% of patients at the 800 and 1000 mg doses.
When OGX-427 was combined with docetaxel, 5 of 10 patients had a decrease in measurable disease of 20% or greater. Five of 9 patients with prostate cancer had a decrease of 30% or greater in PSA. Again, decreases in both total CTCs and Hsp27 (+) CTCs were observed. Hsp27 (+) CTCs were decreased in 71% of evaluable patients. In 4 of 7 patients with ≥ 5 Hsp (+) CTCs at baseline, Hsp (+) CTCs had decreased to ≦ 5 CTCs. Serum Hsp27 protein levels were decreased by 30% or greater over a time period of at least six weeks in approximately 35% of patients.
Click here to view recently presented Phase 1 clinical trial results in superficial bladder cancer.
Click here to view recently presented Phase 2 clinical trial results in castrate-resistant prostate cancer.
This section is intended specifically for healthcare professionals. Information is provided for educational use only, based on pre-clinical and clinical data of OGX-427.
OGX-427 is not approved for commercial use and is only available for investigational use in approved clinical trials.