ArQule, Inc. (NASDAQ: ARQL) and Daiichi Sankyo Co., Ltd. (TSE 4568) today announced the presentation of data from a Phase 2 clinical trial at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO) showing encouraging overall survival (OS) results with ARQ 197 in combination with erlotinib among patients with advanced, refractory non-small cell lung cancer.
“These data from a well controlled trial signal potential patient benefit, with promising overall survival and prolonged progression-free survival”
One hundred sixty-seven patients participated in this Phase 2, double-blind, randomized, signal generation trial. All patients were EGFR (epidermal growth factor receptor) inhibitor-naïve, but had progressed after at least one prior chemotherapy regimen. Patients were randomized one-to-one to receive either the combination of ARQ 197 plus erlotinib or placebo plus erlotinib. The primary endpoint of the study was comparison of Progression-Free Survival (PFS) between treatment arms; secondary endpoints included PFS in pre-defined patient subsets, overall survival, overall response rate, and safety.
The ASCO presentation (Abstract No: LBA7502), given by Joan H. Schiller, M.D., Chief, Division of Hematology and Oncology at the University of Texas Southwestern Medical Center, included data showing that median OS in the intent to treat (ITT) population (n = 167) was 36.6 weeks in the ARQ 197 plus erlotinib arm, compared with 29.4 weeks in the erlotinib plus placebo arm, an improvement of 24 percent (unadjusted hazard ratio = 0.88, p = 0.50) as one of the secondary endpoints.
In the pre-defined sub-group of patients with non-squamous cell carcinoma histology (n = 117), median OS was 43.1 weeks in the treatment arm, compared with 29.4 weeks in the placebo arm, an improvement of 47 percent (unadjusted hazard ratio = 0.72, p = 0.19). Based on an exploratory Cox regression analysis, the difference in median OS achieved statistical significance (p < 0.05) in this sub-group when adjusting for imbalances in key prognostic factors that included EGFR status and KRAS status, both of which favored the placebo arm.
As previously announced, the ARQ 197 plus erlotinib combination demonstrated a 66 percent improvement in the primary endpoint, median Progression-Free Survival (PFS), although the difference in PFS between the two arms did not achieve statistical significance (p = 0.24, hazard ratio = 0.81) by applying a log-rank test. Improvement in median PFS was more pronounced in the pre-defined sub-group of patients with non-squamous histology (n = 117).
"These data from a well controlled trial signal potential patient benefit, with promising overall survival and prolonged progression-free survival," said Dr. Schiller. "In addition, the combination of ARQ 197 plus erlotinib was shown to be well tolerated, with manageable side effects similar to erlotinib alone."
The trial design allowed patients who failed on erlotinib monotherapy to cross over into the erlotinib plus ARQ 197 arm. Of the 23 cross-over patients who were evaluable for response, two had a partial response per Response Evaluation Criteria in Solid Tumors (RECIST) and nine had stable disease.
"These OS results are consistent with the previously reported PFS findings in both the ITT population and patients with non-squamous histology, which gives us additional confidence in the strength of the signal in this trial," said Glenn Gormley, MD, PhD, Chief Scientific Officer & President, Daiichi Sankyo Pharma Development. "The full set of data will now help guide planning for next-stage clinical development activities, as well as discussions with regulatory authorities."
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