A MULTICENTER, OPEN-LABEL PHASE II CLINICAL TRIAL OF COMBINED @entity8047 PLUS XXXX INHIBITION FOR CHEMOTHERAPY-REFRACTORY ADVANCED PANCREATIC ADENOCARCINOMA.

@entity1 @entity788 @entity8047 @entity1124 @entity1910 @entity390 @entity470 @entity5 @entity294 @entity391 @entity5962 @entity16629 @entity17528 @entity3866
PURPOSE: Based on preclinical evidence of synergistic activity between @entity8047 and @entity470 inhibitors in @entity1124 ( @entity1124 ), we evaluated the safety and efficacy of @entity17528 , a @entity16629 inhibitor, plus @entity3866 in @entity1 with previously treated advanced @entity1124 . EXPERIMENTAL DESIGN: In this single-arm phase II trial, eligible @entity1 received the combination of @entity3866 100 mg plus @entity17528 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit. RESULTS: 46 @entity1 were enrolled and received a median of 2 cycles (range, 1-7). While no objective responses were observed, 19 @entity1 (41%) showed evidence of stable disease for >= 6 weeks, and 13/34 @entity1 (38%) had a CA19-9 decline >= 50%. Median progression-free survival was 1.9 months (95% CI, 1.4-3.3 months), with a median OS of 7.3 months (95% CI, 5.2-8.0 months). Common adverse events included @entity1910 , @entity294 , and @entity390 / @entity391 . @entity1 with @entity5 exhibiting an epithelial phenotype (demonstrated by high level of @entity5962 expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of @entity1 using next-generation digital DNA sequencing, and its relative abundance correlated with @entity5 burden. CONCLUSIONS: A therapeutic strategy of dual targeted inhibition of the @entity8047 and @entity470 pathways shows modest antitumor activity in @entity788 . Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent @entity8047 inhibitors and in molecularly enriched @entity1 subsets, is warranted.
