Efficacy of the anti-insulin like growth factor I receptor (IGF-IR) antibody CP-751871 in combination with paclitaxel and carboplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC)

摘要: 7506 Background: CP-751871 is a fully human, IgG2 monoclonal antibody against the IGF-IR active in preclinical models of NSCLC. Methods: We are conducting a phase II, randomized, non-comparative study in ten centers to evaluate the safety and efficacy of combination paclitaxel (T), carboplatin (C) and CP-751871 (I) versus TC alone in stage IIIB, IV or recurrent, treatment-naive NSCLC pts with performance status 0–1. The statistical hypotheses are 28% (null) versus 40% (response of interest). Pts are randomized (2:1) to T (200 mg/m2), C (AUC of 6) and I (10 mg/kg), or TC alone every 3 weeks for up to 6 cycles; pts receiving TCI with response (PR) or stable disease following discontinuation of chemotherapy are eligible to continue I as single agent until disease progression. Pts progressing on TC alone are eligible to receive I as single agent or in combination with TC at the judgment of the investigator. Responses are assessed by investigator using RECIST. Results: An interim analysis for futility has been conducted with 73 pts enrolled: 48 treated with TCI; 25 with TC. TCI was well tolerated. All causality grade 3,4 toxicity included (TCI, TC): hyperglycemia (20%, 10%), fatigue (15%, 8%), neutropenia (13%, 20%) and neuropathy (10%, 4%). 22/48 pts receiving TCI (46%) and 8/32 pts on TC (32%) had objective responses. Furthermore, 14 out of 27 TCI pts (52%) with non-adenocarcinoma responded to treatment. In addition, a PR was observed in 1 out of 4 TC pts who elected to receive single agent I after progression on TC alone. Conclusions: CP-751871 appears safe in combination with TC. Interim TCI activity warranted further investigation. An additional 83 pts will be enrolled to assess further the safety and efficacy of this combination treatment. [Table: see text]