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17098 Background: NSCLC is the leading cause of cancer mortality for men and women in the United States. More effective treatments are needed to prolong survival and improve quality of life. Platin-containing chemotherapy doublets are commonly used in NSCLC treatment. ABT-751 is a novel oral anti-microtubule agent targeting the colchicine binding site. As single agent, it was well-tolerated and showed a preliminary signal of activity in previously treated NSCLC. In vivo studies demonstrated additive activity between ABT-751 and cisplatin in a NSCLC xenograft model. Methods: A phase I trial of ABT-751 and C was conducted in pts with advanced previously treated NSCLC. Primary objective - maximum tolerated dose (MTD). Secondary objectives - toxicities, efficacy, and surrogate markers of response (cell cycle changes and cyclin D1 expression) in buccal swabs from pts at the phase II dose. Six dose levels - 1: ABT-751 100mg bid, C AUC 4.5; 2: ABT-751 125 mg bid, C AUC 4.5; 3: ABT-751 125 mg bid, C AUC 6; 4: ABT-751 150 mg bid, C AUC 6; 5: ABT-751 175 mg bid, C AUC 6; 6: ABT-751 200 mg bid, C AUC 6. ABT-751 was taken orally twice a day for 14 days in a 21 day cycle, C was administered intravenously on day 4 during cycle 1 and on day 1 on subsequent cycles. Rapid dose escalation was used for the first 3 dose levels followed by cohorts of at least 3 patients for the remaining dose levels. Results: Eight pts were enrolled, all stage IV NSCLC, 4 women, median age 62 (47–73), all KPS 80, 6 had one and 2 had 2 prior therapies. A median of 3.5 (1–4) cycles was administered. Dose-limiting toxiticies of grade 3 fatigue and grade 4 thrombocytopenia and neutropenia were observed in 2/5 patients on dose level 4. Common grade 2 toxicites were constipation and peripheral sensory neuropathy (levels 2–4). MTD was dose level 3. Seven pts were evaluable for response, 2 had partial responses (levels 2 and 4, both had one prior therapy), 4 had stable disease, 1 had disease progression. Median time to progression was 18.7 weeks (6–24+). Pharmacokinetic analyses and buccal swabs are being performed. Conclusions: The recommended phase II doses are ABT-751 125 mg twice daily for 14 days and carboplatin AUC 6 on a 21-day cycle. This regimen is well tolerated and shows preliminary evidence of activity for previously treated NSCLC. [Table: see text]

e19090 Background: Taxanes continue to play an important role in the treatment of advanced NSCLC. Paclitaxel poliglumex (XyotaxTM) is an ester α-poly-L-glutamic acid conjugate of paclitaxel allowing for solubility in aqueous solution, not requiring Cremophor or ethanol for intravenous administration or premedications. This is a non-randomized single-arm, single-institution open label dose-ranging study was designed to evaluate the combination of pemetrexed and paclitaxel poliglumex. Methods: The primary objective of this study was to evaluate the safety of this combination. Patients (pts) were enrolled in 2 different dosing levels. The first 6 received 135 mg/m2 paclitaxel poliglumex and 500 mg/m2 pemetrexed intravenously every 3 wks. None of the 6 pts experienced an initial dose limiting toxicity (IDLT) following 2 cycles of therapy and the paclitaxel poliglumex was then escalated to 175 mg/m2 with 500 mg/m2 pemetrexed. Eligibility included advanced NSCLC, one or more measurable lesions (RECIST), ECOG = 0–2, prior chemotherapy and radiation allowed, no grade 2+ peripheral neuropathy, no untreated brain metastases, and no active cardiac disease. Results: Twelve pts were enrolled, 6 pts to each dose level. Four of the pts were female, the median age was 65 years (48- 74), 11 had a performance status of 0–1, and only 1 pt received prior chemotherapy. There were no IDLTs at the first dose level, and there was one IDLT of infection with neutropenia at the second dose level. The median number of cycles completed was 5 (range 1–12 cycles). Aside from grade 3 fatigue in 2 pts there were no grade 3 or greater non-hematologic toxicities. Common non-hematologic toxicities included peripheral neuropathy, constipation, fatigue, and alopecia. Of the 12 pts, the best response was stable disease in 9 pts, 2 are without disease progression, and 6 pts are alive to date. The median progression free survival was 3.3 months (range 0.7–10.7 months). Conclusions: The combination of paclitaxel poliglumex and pemetrexed was well tolerated at the proposed phase II dose of 175 mg/m2 and 500 mg/m2. The PFS is encouraging and future studies of this combination are recommended. No significant financial relationships to disclose.