BACKGROUND:Treatment options for patients with advanced head and neck squamous cell carcinoma (HNSCC) are scarce. This phase 2 study was conducted to evaluate the safety, tolerability, pharmacokinetics, and efficacy of dasatinib in this setting. METHODS: Patients with recurrent and/or metastatic HNSCC after platinum-based therapy were treated with dasatinib either orally or via percutaneous feeding gastrostomy (PFG). Primary endpoints were 12-week progression-free survival (PFS) and objective response rate with a 2-stage design and early withdrawal if the 12-week PFS rate was 20% and no patients had an objective response (OR). Forty-nine serum cytokines and angiogenic factors (CAFs) were analyzed from treated patients. RESULTS: Of the 15 patients enrolled, 12 were evaluable for response, and all patients were evaluable for toxicity. No OR was observed and 2 patients (16.7%) had stable disease (SD) at 8 weeks. The median treatment duration was 59 days, the median time to disease progression was 3.9 weeks, and the median survival was 26 weeks. One patient required a dose reduction, 3 patients required dose interruptions, and 4 patients were hospitalized for toxicity. Dasatinib inhibited c-Src both when administered orally and via PFG. Greater mean drug exposure, decreased half-life, and greater maximum concentration were observed in patients receiving dasatinib via PFG. Eleven baseline CAFs were associated with treatment outcome and 1 CAF, macrophage migration inhibitory factor, was found to be differentially modulated in correlation with SD versus disease progression. CONCLUSIONS: Single-agent dasatinib failed to demonstrate significant activity in patients with advanced HNSCC, despite c-Src inhibition. The toxicity profile was consistent with that reported in other solid tumors, and the drug can be given via PFG tube.

SummaryIbrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti‐CD20 monoclonal antibody with single‐agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2–6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty‐one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high‐risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long‐term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

7502 Background: Chemoresistant patients with FL and those who progress within 2 y after initial diagnosis have poor outcomes (Casulo. JCO. 2015) and highlight an unmet need. Methods: MAGNIFY (NCT01996865) is a phase IIIb, multicenter, open-label study of relapsed/refractory (R/R) NHL patients, including grades 1-3b or transformed FL (tFL). Patients receive 12 cycles of lenalidomide plus rituximab (R2); those with stable disease or better are randomized 1:1 to maintenance R2 or rituximab alone. The primary endpoint is progression-free survival (PFS). This analysis focuses on FL: double-refractory (DR) patients are refractory to both rituximab (as monotherapy or combination) and an alkylating agent, and early relapse (ER) patients progressed or relapsed within 2 y of initial diagnosis. Results: As of July 19, 2016, the R/R FL population (N = 117) included 32 (27%) DR and 43 (37%) ER patients, median ages of 64 and 65 y, respectively, mostly grade 1-3a FL (94%; 91%) and 2 tFL (1 DR; 1 ER); 72% and 49% were stage IV at study entry. Patients had a median of 2 prior regimens (DR 3; ER 2). Of ER patients, 31 had first-line R-chemo vs 12 with R-mono/other. Response rates are in Table 1. Median time to response was 2.8 mo for DR and 2.7 mo for ER patients, with median duration not reached. 1-y PFS for FL patients was 66% (DR 66%; ER 45%); 1-y PFS for ER patients with first-line R-chemo was 50% vs 27% in others. Common grade ≥3 treatment-emergent AEs for DR and ER patients were neutropenia (53%; 33%), leukopenia (9%; 12%), and lymphopenia (9%; 5%). Conclusions: R2 followed by maintenance showed favorable activity and tolerable safety profiles in FL patients who are double-refractory or had early relapse ( < 2 years) after initial diagnosis. Enrollment in MAGNIFY is ongoing. Clinical trial information: NCT01996865. [Table: see text]

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