CPG 7909, a TLR9 agonist, added to first line taxane/platinum for advanced non-small cell lung cancer, a randomized, controlled phase II study

Abstract

7039 Background: First line treatment for stage IIIb/IV NSCLC continues to be a combination of a taxane + platinum with partial responses expected in only 20 - 30% of patients. Multiple pre-clinical models have shown that tumor response and survival after chemotherapies are significantly improved by the addition of CPG 7909. This new synthetic oligodeoxynucleotide acts through dendritic cells by targeting the Toll-like Receptor 9 with subsequent immunomodulatory effects. Human dose ranging, safety and biologic responses to weekly S.C. doses of CPG 7909 have been established in earlier trials. Methods: This phase II trial randomized and treated 112 patients in 23 centers. Naïve patients with NSCLC were randomized 2:1 and received 4 - 6 three-week cycles of a standard regimen of taxane and platinum plus CPG 7909 [C + CPG 7909] on weeks 2 and 3 of each cycle or [C] alone. Each dose of CPG 7909 was 0.20 mg/kg given S.C. The primary endpoint of objective response was assessed at cycles 2, 4 and 6 using RECIST criteria. A post-hoc independent radiological review [IRR] was conducted on coded and blinded scans. Secondary efficacy analyses are being completed, and include clinical benefit, time to and duration of response, and survival. Biomarker responses to CPG 7909 will be compared for responders vs non-responders in the two arms. Results: Data for an ITT response analysis are available on 83 patients from the planned protocol (57 vs 26). Baseline demographics are balanced except for more stage IV patients in the C + CPG 7909 group. Administration of CPG 7909 did not complicate standard cycles of [C]. ORR was 23% vs 40% for the [C] vs [C+CPG 7909] arms, and is supported by the retrospective IRR data. Kaplan-Meier curves show a trend to improved PFS and survival in [C + CPG 7909] compared to [C]. A complete analysis including follow up survival will be presented on the 83 planned patients plus 28 patients more recently enrolled in a protocol amendment. Conclusions: A well tolerated regimen of weekly CPG 7909 added to a taxane/platinum regimen for first line treatment of NSCLC appears to improve objective response, and pivotal studies are warranted to document clinical benefit of this new modality. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group