Lessons from Conducting Mouse Clinical Trial (MCT) on a Cohort of NSCLC Patient Derived Xenografts (Pdxs).

e18505 Background: Patient-derived xenograft (PDX) is increasingly used to evaluate oncology drugs. PDX, reflective of original patient pathology and genomics, is predictive of response to treatment. Cohort of PDX mirror diversity of corresponding patient populations. Mouse clinical trial (MCT) on cohort of PDXs (randomized, controlled and statistically powered, as in human trial) can potentially guide clinical development or use of cancer therapy. Methods: We previously described a cohort of NSCLC PDXs (>200)1 and now are conducting mouse clinical trials by randomly enrolling PDX subjects from this cohort to assess antitumor activities of 3 drugs, cisplatin, paclitaxel and X per method described previously2. We assessed the antitumor activity using various clinically relevant endpoints (DT/DC, RECIST, OS, PFS), and evaluated information gain from the MCT to guide clinic use of these agents. Results: Two chemotherapy demonstrated statistic significant anti-tumor activities in the cohort with medium PFS of 41 days for paclitaxel, 37 days for cisplatin and 28 days for placebo. The differences between the two treated vs. placebo are significant (p-values 0.001 and 0.03 respectively), but not significant between the two treated (p-value of 0.47). OS analysis yielded the same conclusions (medium 95, 67 and 41 days, respectively, p-value <0.001, 0.002 and 0.23 in the same order). Analysis revealed that 2 agents’ activity do not overlap among the individuals, implying: 1) subjects resistant to one (e.g. 1st line treatment) might still respond another (2nd line treatment); 2) the combination of these 2 makes sense for the diseases. Due to all these models have been genomic-profiled, it is also possible to identify markers predictive of response. Similarly, an investigational agent X was found to have superior activity over both cisplatin and paclitaxel in the same cohort. Its activity overlaps with neither, suggesting it can potentially be developed as either 1st or 2ndline treatment in clinical development. Conclusions: Our study indicated that MCT could be a powerful tool to guide clinical use and development of new cancer agents.