Efficacy and safety of risankizumab in Japanese patients with generalized pustular psoriasis or erythrodermic psoriasis: Primary analysis and 180-week follow-up results from the phase 3, multicenter IMMspire study.

Risankizumab, a humanized immunoglobin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, is approved in Japan to treat numerous indications, including generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). Both GPP and EP are severe forms of psoriasis that have limited treatment options. In IMMspire (A Study to Assess Efficacy and Safety of Two Different Dose Regimens of Risankizumab Administered Subcutaneously in Japanese Subjects With Generalized Pustular Psoriasis or Erythrodermic Psoriasis) (NCT03022045), a phase 3, randomized, multicenter study in Japan, we evaluated the efficacy and safety of risankizumab for Japanese adults with GPP or EP. Patients were randomized (1:1) to receive open-label risankizumab 75 mg or 150 mg at weeks 0 and 4 and every 12 weeks thereafter through week 160. The primary efficacy end point was GPP or EP clinical response at week 16. Other efficacy end points included GPP or EP clinical response, ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Dermatology Life Quality Index of 0 or 1 (DLQI 0/1) through 180 weeks (last follow-up visit). Safety was assessed throughout. A total of 17 patients (eight with GPP and nine with EP) were enrolled. All patients achieved the primary end point of GPP or EP clinical response at week 16. Among patients continuing risankizumab treatment, achievement of GPP or EP clinical response, PASI 90 and DLQI 0/1 were generally sustained throughout the treatment. The safety profile remained consistent with the safety profiles noted in previous risankizumab studies. Risankizumab demonstrated clinically meaningful efficacy at week 16, with durable efficacy and a favorable long-term safety profile in Japanese patients with GPP or EP.

Phase I safety and pharmacokinetics study of rovalpituzumab tesirine in Japanese patients with advanced, recurrent small cell lung cancer.

OBJECTIVES: Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) on small cell lung cancer (SCLC) tumors, is internalized and releases the toxin pyrrolobenzodiazepine to induce cell death. This open label phase I study was the first study of Rova-T in Japanese patients. The aim of this study was to evaluate, safety, pharmacokinetics, and preliminary efficacy of Rova-T in Japanese patients with advanced recurrent SCLC. MATERIALS AND METHODS: Patients received Rova-T (0.2 or 0.3 mg/kg) by intravenous infusion on Day (D) 1 of each 6-week cycle for 2 doses and dexamethasone (8 mg BID oral) on D-1, D1, and D2 of each 6-week cycle. Retreatment with Rova-T was permitted for patients who tolerated their initial doses and then progressed after disease control (defined as stable disease or better) was observed for at least 12 weeks after their last dose of Rova-T. RESULTS: Rova-T exhibited toxicity that was generally manageable in Japanese patients (N = 29). No dose-limiting toxicities were experienced. The most common treatment-related adverse events (≥25% of patients, all grades) were platelet count decreased, pleural effusion, peripheral edema, aspartate aminotransferase increased, white blood cell count decreased, neutrophil count decreased, alanine aminotransferase increased, hypoalbuminaemia, anemia and decreased appetite. Safety and pharmacokinetics exposures were similar to previous observations in non-Japanese populations. Per investigator assessment of DLL3 high patients, 17% (3/18) had confirmed partial responses, and the disease control rate was 56%, mPFS was 2.9 months, and mOS was 7.4 months. CONCLUSIONS: These preliminary data support further exploration of Rova-T treatment in Japanese patients with SCLC in global studies. This trial was registered with ClinicalTrials.gov as NCT03086239.