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K. Anderson
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-098 - Addition of Custirsen, a Clusterin Inhibitor, to Docetaxel in Stage IV Non-Small Cell Lung Cancer (NSCLC): The ENSPIRIT™ Phase 3 Trial (ID 2192)
09:30 - 09:30 | Author(s): K. Anderson
- Abstract
Background:
Treatments that improve overall survival (OS) in advanced NSCLC are urgently needed. Docetaxel (DOC) is recommended as 2[nd]-line chemotherapy for advanced NSCLC, with a median OS of 7-8 months. The chaperone protein clusterin (CLU) is upregulated in NSCLC and other cancers in response to anticancer therapies. Custirsen (OGX-011) is a second-generation antisense oligonucleotide that inhibits CLU expression, enhances chemotherapeutic activity, and in vivo has reversed DOC resistance. In early phase studies in metastatic castration resistant prostate cancer (mCRPC), custirsen plus DOC was well tolerated and showed encouraging results. In a phase 3 mCRPC study (SYNERGY), 50% of patients defined as poor prognosis had survival benefit from custirsen when added to 1[st]-line DOC.
Methods:
ENSPIRIT was initiated September 2012. Eligible patients in this phase 3, multinational, open-label trial have failed 1 prior line of platinum (PT)-based therapy, have an ECOG of 0-1, and adequate bone marrow, renal, and liver function. Randomization is 1:1, with stratification by gender, NSCLC histology, best response to 1[st]-line PT therapy (response/stable disease vs progression), and ECOG score. Patients receive 21-day cycles of DOC (75 mg/m[2] IV day 1) or DOC plus custirsen (640 mg IV/wk, preceded by 3 doses during a 9-day loading period) until progressive disease, unacceptable toxicity, or withdrawal. The primary efficacy measure is OS. Two interim analyses are planned for stopping the trial based on inadequate evidence of clinical benefit or futility; the first futility analysis was completed in August 2014. A recent amendment changed the hypothesized hazard ratio for the primary analysis from 0.80 to 0.75 (power remains at 90%), resulting in a required sample size of 700 patients (instead of original 1100). In addition, the second futility has a more rigorous criterion for stopping due to survival futility and is to occur earlier than originally planned. The study will not be stopped early for efficacy. The aim of the ENSPIRIT amendment is to assess for a more clinically relevant survival benefit when adding custirsen to 2[nd]-line DOC or terminate the trial early for survival futility.
Results:
Not applicable.
Conclusion:
Not applicable.
