Pts 20206/1/2023 ![]() ![]() Results: As of Sept 2, 2019, 27 pts were enrolled: 24 discontinued (18 due to disease progression 67%), 3 were ongoing. Pre- and on-treatment pt samples were collected: skin samples for RT-PCR analysis of AXIN2, a marker of Wnt pathway activity tumor samples for RNAseq of AXIN2 and immune cell markers. Objectives were to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE), safety, pharmacokinetics (PK), pharmacodynamics, and activity of WNT974 + spartalizumab. WNT974 was dosed orally QD in 28-day cycles (2.5-10 mg, Days 1-8 or 1-15 of Cycles 1 or 1-4) spartalizumab was dosed IV at 400 mg Q4W. ![]() Pts with melanoma, lung SCC, or HNSCC must have had a best response of progressive disease (primary refractory) to prior αPD-1 therapy other pts were naïve or primary refractory to prior αPD-1. Eligible pts had melanoma (including uveal), lung SCC, HNSCC, esophageal SCC, cervical SCC, or TNBC. Methods: In this Phase I, open-label trial (NCT01351103) adult pts received WNT974 ± spartalizumab here we report on the dose escalation of the combination. Spartalizumab is an αPD-1 mAb with demonstrated clinical activity in solid tumors. Dysregulated Wnt signaling has been linked to immunotherapy resistance, suggesting WNT974 may act synergistically with checkpoint inhibitors. ![]() ![]() Background: WNT974, a Porcupine inhibitor, has shown evidence of Wnt pathway inhibition in clinical trials. ![]()
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