Abstract
<div>AbstractPurpose:<p>In this phase Ib/II study, we aimed to evaluate the safety and efficacy of PDR001, an anti-PD1 antibody, in combination with imatinib in patients with treatment-refractory gastrointestinal stromal tumor (GIST).</p>Patients and Methods:<p>Patients with advanced GIST whose disease had progressed on imatinib, sunitinib, and regorafenib were enrolled. In phase Ib, the standard 3 + 3 dose escalation scheme was applied. Intravenous administration of PDR001 at 400 mg for every 4 weeks plus imatinib (300 and 400 mg daily for dose levels I and II, respectively) was given. The primary outcome for phase II was the disease control rate at 12 weeks. Exploratory biomarker analysis was performed based on PDL1 IHC, next-generation sequencing, and multiplexed IHC.</p>Results:<p>No dose-limiting toxicity was observed in the phase Ib part (<i>n</i> = 10), and dose level II was selected as the recommended phase II dose. In the phase II part (<i>n</i> = 29), there was no objective response, and the disease control rate at 12 weeks was 37.9%, not meeting the primary efficacy endpoint. For patients in phase Ib–dose level II and phase II (<i>n</i> = 36), the median progression-free survival (PFS) and overall survival were 2.3 and 9.5 months, respectively. The most common grade 3 to 4 adverse event was anemia. Exploratory biomarker analysis indicated that a higher CD8<sup>+</sup> T-cell density was associated with a favorable PFS but to a limited degree. Tumor mutational burden and PDL1 were not associated with better PFS.</p>Conclusions:<p>In patients with treatment-refractory GIST, PDR001 in combination with imatinib was generally tolerable, but it was not effective.</p></div>
Published Version
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