• Once-daily oral avatrombopag dose-dependently raised PCs over 28 days, with stable counts maintained over a 24-week extension.• Low rates of severe AEs and study drug discontinuations due to AEs occurred despite dose increases in maintenance.Stimulation of platelet production by thrombopoietin-receptor agonists (TPO-RAs) is an effective second-line treatment in immune thrombocytopenia (ITP). This 28-day phase 2 study assigned subjects with ITP of ‡3 months to once-daily oral avatrombopag (2.5, 5, 10, or 20 mg), an investigational nonpeptide TPO-RA active in humans, or placebo; subjects completing randomized treatment could enroll in a 24-week extension study. Of 64 randomized subjects, 13% (avatrombopag 2.5 mg), 53% (5 mg), 50% (10 mg), and 80% (20 mg), vs 0% for placebo, achieved a platelet count (PC) response of ‡50 3 10 9 /L with ‡20 3 10 9 /L increase above baseline at day 28. Fifty-three subjects (83%) entered the extension: 52% and 76% had a durable (PC response at ‡75% of their platelet assessments over the last 14 weeks) and overall (stable response or response at any ‡2 consecutive visits) response, respectively. All subjects experienced ‡1 adverse event (AE) (most commonly fatigue, headache, and epistaxis); 19% (n 5 12) reported ‡1 serious AE; 10 (16%) withdrew due to an AE (5 due to increased PC). Avatrombopag was active and generally well tolerated, with PC response rates and AE incidence comparable with other TPO-RAs. These studies were registered at www.clinicaltrials.gov as #NCT00441090 and

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Purpose LY3022859 is an anti-TGFβRII IgG1 monoclonal antibody that inhibits receptor-mediated signaling activation. The primary objective of this phase I study was to determine a phase II dose in patients with advanced solid tumors. Secondary objectives were to assess safety and pharmacokinetics (PK). Methods LY3022859 was infused intravenously (IV) at 1.25 mg/kg over 1 hour every 2 weeks (Q2W) (cohort 1A) and at flat doses of 12.5 mg (cohort 1B) and 25 mg (cohort 2) over 3 hours Q2W. Results Fourteen patients were enrolled in cohorts 1A (n=2), 1B (n=5), and 2 (n=7). DLTs were experienced by both patients in cohort 1A (infusion-related reaction) and 2 patients in cohort 2 (cytokine release syndrome and infusion-related reaction). No MTD was determined. At the 25 mg dose level (cohort 2), after fifth infusion, LY3022859 had a short t1/2 (4.37–7.80 hours) and rapid clearance (CLss, 0.412 L/hr). Exposure increased 2-fold (from 28.5 μg·hr/mL to 60.2 μg·hr/mL) with increase in dose from 12.5 mg to 25 mg. No accumulation was observed after repeat administration. Conclusions The MTD for LY3022859 was not determined. Dose escalation beyond 25 mg was considered unsafe due to worsening symptoms (uncontrolled cytokine release) despite prophylaxis (corticosteroids, antihistamines).

The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.