Phase II study of NK012 in relapsed small cell lung cancer.

Abstract

7079 Background: NK012 is a topoisomerase I (TI) inhibitor designed as a micelle-forming macromolecule to release a gradual and sustained concentration of SN-38, the active metabolite of irinotecan. Phase I studies have shown safety and antitumor activity of NK012 in patients (pts) with refractory tumors including small-cell lung cancer (SCLC). This phase II trial was designed to evaluate NK012 in pts with sensitive relapsed (SR) and refractory relapsed (RR) SCLC. Methods: Pts with relapsed SCLC following 1 chemotherapy regimen for extensive-stage SCLC or chemoradiation for limited-stage SCLC were eligible. Pts had measurable disease, an ECOG performance status (PS) of 0-2, and adequate organ function. Pts with untreated brain metastases or prior TI therapy were excluded. NK012 was given IV over 30 minutes once every 28 days at a dose based on pretreatment UGT1A1 genotyping: 28 mg/m2 (wild-type [wt]/wt and wt/*28) or 18 mg/m2 (*28/*28). Pts were restaged every 8 weeks and remained on therapy until disease progression or unacceptable toxicity. The trial used a two-stage design to assess the objective response rate (ORR) in both SR (H1 30%, α.10, β.20) and RR cohorts (H1 20%, α.05, β.20). Results: 40 SR pts were enrolled over 11 months. The RR cohort remains open to enrollment. Pt characteristics of the SR pts: median age 62 years, female 48%, ECOG 0-1 95%. Pts received a median of 4 cycles (range 1-10) of NK012. The ORR assessed in 37 SR pts was 22% including 2 complete responses; the disease control rate (DCR=ORR+stable disease) was 68%. Survival analyses are in progress. NK012 was well-tolerated with the following grade 3/4 toxicities (> 5%): neutropenia (44%, 1 pt with febrile neutropenia), thrombocytopenia (13%), anemia (5%), diarrhea (8%), and no treatment-related deaths. Conclusions: NK012 exhibited positive efficacy in pts with sensitive relapsed SCLC with a 22% ORR and a 68%DCR. Toxicity was expected and manageable with relatively low rates of serious toxicity. NK012 is currently in a phase I platinum combination study.