PX-866 and docetaxel in patients with advanced solid tumors (ASCO 2012) - May 16, 2012 - Presentation time: Saturday June 2, 1:15 PM to 5:15 PM; P1, N=43; PX-866-002; Best response in 32 evaluable pts was 2 PR (6%), 22 SD (69%) & 8 PD (25%); The PRs were in NSCLC & ovarian cancer (both PIK3CA/KRAS WT). 8 other pts had ≥15% tumor shrinkage, including NSCLC (n=2); PX-866 with docetaxel was associated with a disease control rate of 75%, with 50% of evaluable pts demonstrating SD or better for ≥ 6 cycles
P1 data • Non Small Cell Lung Cancer • Pancreatic Cancer
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2012 American Society of Clinical Oncology Annual Meeting, Jun 1-5, 2012, Chicago, IL
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Abstract # 3024
Background: PX-866, an irreversible pan-isoform inhibitor of Class 1 PI-3K has additive to synergistic effects when combined with docetaxel in xenograft models of NSCLC and SCCHN. A phase I/II study of PX-866 and docetaxel was initiated to further evaluate this combination. Enrollment in phase I is complete, and the randomized, controlled phase II portion is now enrolling patients with either NSCLC or SCCHN. Phase I safety and pharmacokinetics were previously described; the recommended phase II dose of PX-866 was 8 mg daily, the same as the single agent MTD (Jimeno A, et al. AACR-NCI-EORTC, 2011). Updated phase I antitumor and biomarker results are presented here. Methods: Phase 1 consisted of dose escalation of PX-866 at 4, 6, or 8 mg po qd in combination with docetaxel 75 mg/m2 IV once every 21 days (d). Patients had advanced solid tumors for which docetaxel was compendia listed. Tumor restaging was performed every 2 cycles. Archived tumor biopsies were collected for assessment of potential biomarkers of response, including PIK3CA and KRAS mutations and PTEN expression. Results: 43 pts were enrolled: NSCLC (n=6), prostate (n=5), ovarian (n=5), SCCHN (n=3), and pancreatic (n=3) were the most common tumor types. Median time on study (TOS) was 81 d (5-361), with 9 pts still on study. 16 pts received ≥ 6 cycles (6-17), including 3 pts with NSCLC, and 4 pts with ovarian cancer. Biomarker data are available for 20 evaluable pts. Median days on study by mutational status was: PIK3CA/KRAS WT (n=13): 91 d (28-286); PIK3CA-MUT (n=5): 183 d (64-342); KRAS-MUT (n=3): 141 d (125-361); and PIK3CA/KRAS-MUT (n=2): 96 d (86-105). A trend toward longer TOS was observed in pts with PIK3CA-MUT vs PIK3CA/KRAS-WT (p=0.14). Assessment of PTEN is ongoing. Best response in 32 evaluable pts was 2 PR (6%), 22 SD (69%), and 8 PD (25%). The PRs were in NSCLC and ovarian cancer (both PIK3CA/KRAS WT). 8 other pts had ≥15% tumor shrinkage, including NSCLC (n=2). Conclusions: PX-866 with docetaxel was associated with a disease control rate of 75%, with 50% of evaluable pts demonstrating SD or better for ≥ 6 cycles. Based on available data, a trend for a longer TOS was seen with PIK3CA-MUT pts. This relationship will be further evaluated in phase II.
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