L-BLP25 maintenance therapy in patients with advanced NSCLC is feasible with minimal toxicity. The survival difference of 4.4 months observed with the vaccine did not reach statistical significance. In the subgroup of patients with stage IIIB LR disease, a strong trend in 2-year survival in favor of L-BLP25 was observed.
Confirming the initial results, further follow-up continues to show that survival time for patients with stage IIIB/IV NSCLC was longer with L-BLP25 plus BSC compared with BSC alone, with the greatest difference seen in patients with stage IIIB LR disease.
Background: The clusterin gene is frequently expressed in NSCLC and encodes a cytoprotective chaperone protein that is upregulated in response to apoptotic stimuli such as chemotherapy. OGX-011 is a second-generation antisense oligonucleotide that inhibits clusterin expression, thus enhancing the apoptotic effects of chemotherapy. Previous phase I studies with docetaxel suggested an OGX-011 dose of 640mg was feasible and biologically active; therefore, the current study began with a run-in phase with 480mg of OGX-011. Methods: Eligibility criteria: stage IIIB/IV NSCLC; no prior chemotherapy; ≥ 1 measurable lesion; ECOG ≤1; adequate organ function; no active CNS metastasis. Treatment: OGX-011 is given as a 2-hour infusion. There is an initial loading phase with 3 doses of OGX-011 alone in 1 week, followed by weekly OGX-011 with standard chemotherapy: gemcitabine (1250 mg/m 2) Days 1+8 and either cisplatin (75 mg/m 2) or carboplatin (AUC=5) Day 1 q21 days, (maximum 6 cycles). Results: 85 pts (phase 1=10 and phase 2=75) were enrolled between Dec, 2004 and Nov, 2006. As no unexpected dose limiting toxicities were noted in the first 3 patients who received 480mg of OGX-011, the dose was escalated, as planned, to 640 mg for the remaining patients. Data are available on the first 53 pts; all received ≥1 dose of OGX-011 and were considered evaluable for safety and efficacy. Demographics: female (47%); stage IV (87%); median age 61 (45-79) yrs; ECOG PS = 1 (62%). The median number of cycles delivered was 4. Principal grade 3/4 toxicities were hematologic: neutropenia (32%) + thrombocytopenia (17%). Other common toxicities included fatigue, nausea, vomiting, fever, chills, constipation, + anorexia. Two Serious Adverse Events previously reported as associated with gemcitabine/platinum therapy were documented: acute cortical blindness with stroke + thrombotic thrombocytopenic purpura. Responses: confirmed PRs 13 (ORR = 24%); median duration of PR: 105 days (46-336+); median PFS: 140 days (2-422+); 79% of pts have progressed; 47% have died. Of the first 34 patients who have all been followed for ≥ 1 yr, 18/34 (53%) survived > 1 yr; 14/18 (78%) remain alive as of March 06, 2006. Data will be presented for all 85 patients. Conclusions: This combination is feasible and tolerable. The 1-yr survival rate ≥50% may justify a randomized phase III trial. OGX-011 is being developed by OncoGenex Technology Inc. + Isis Pharmaceuticals Inc.
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