B1-01: A multi-centre phase IIB randomized controlled study of BLP25 liposome vaccine (L-BLP25 or Stimuvax) for active specific immunotherapy of non-small cell lung cancer (NSCLC): updated survival analysis

Abstract

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.

Vaccines for the treatment of non-small cell lung cancer: Investigational approaches and clinical experience

“…The greatest survival benefit was observed in patients with stage IIIB locoregional disease. A subsequent updated survival analysis in these patients after median follow-up times of 53 months (L-BLP25 arm, n = 35) and 57 months (BSC arm, n = 30) revealed median survival times of 30.6 months and 13.3 months for the L-BLP25 and BSC arms, respectively (adjusted HR 0.55, 95% CI 0.30-1.00; p = ns) [83]. In the same patients the two-year and three-year survival rates were 57% and 49%, respectively, in the L-BLP25 arm, and 33% and 27%, respectively, in the BSC arm [83].…”

Therapeutic cancer vaccines: a long and winding road to success

“…Stimuvax (L-BLP25) is a cancer vaccine designed to induce an immune response against the extracellular core peptide of MUC1, a Type 1 membrane glycoprotein widely expressed on many tumors. In a randomized Phase IIb trial of Stimuvax in patients with stage IIIb locoregional NSCLC after response to primary chemotherapy, the 2-year survival rate for vaccinated patients was 60% compared with 36.7% in the best supportive care arm [52,53]. The Phase III START study of L-BLP25 with NSCLC patients in remission after chemoradiotherapy (CRT) did not meet its primary endpoint which was OS.…”

Current Trends in Cancer Vaccines - a Bioinformatics Perspective

“…STIMUVAX is designed to stiumalte immune response against the MUC 1 (glycoprotein widely expressed in tumors of lung cancer, breast cancer, prostate cancer and colorectal cancer). The clinical trials conducted against the Non-small cell lung cancer patients (NSCLC) using the STIMUVAX signals the efficacy of the vaccine (Butts et al, 2007).…”