Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma.

Epcoritamab is a subcutaneously administered CD3xCD20 bispecific Ab that showed deep, durable responses with a manageable safety profile in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the global multicenter pivotal phase II trial EPCORE NHL-1. Here, we present results from the similar EPCORE NHL-3 phase I/II trial evaluating epcoritamab monotherapy in Japanese patients with R/R CD20+ B-cell non-Hodgkin's lymphoma previously treated with two or more lines of therapy. Epcoritamab was dosed subcutaneously in 28-day cycles; once weekly during cycles 1-3, every 2 weeks during cycles 4-9, and every 4 weeks from cycle 10 until disease progression or unacceptable toxicity. Step-up dosing and cytokine release syndrome (CRS) prophylaxis were used during treatment cycle 1. As of January 31, 2022, 36 patients received treatment with 48 mg epcoritamab monotherapy. At a median follow-up of 8.4 months, overall response and complete response rates by independent review committee were 55.6% and 44.4%, respectively. The median duration of response, duration of complete response, and overall survival were not reached at the time of data cut-off. The most common treatment-emergent adverse events of any grade were CRS (83.3%), injection-site reactions (69.4%), infections (44.4%), neutropenia (38.9%), hypokalemia (27.8%), and decreased lymphocyte count (25.0%). Cytokine release syndrome occurrence was predictable; events were primarily low grade (grade 1-2), all resolved, and none led to treatment discontinuation. These encouraging results are consistent with previous findings and support the ongoing clinical evaluation of epcoritamab for the treatment of R/R DLBCL, including in earlier treatment lines.

Patient perceptions of psoriatic disease in Japan: Results from the Japanese subgroup of the Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey.

The population-based Understanding Psoriatic Disease Leveraging Insights for Treatment (UPLIFT) survey was designed to better understand patient and dermatologist perceptions of the disease burden of psoriasis (PsO) and their treatment expectations. UPLIFT was a cross-sectional, quantitative, online survey conducted in Europe, North America, and Japan between 2 March and 3 June 2020. In Japan, 391 patients reporting a diagnosis of PsO and/or psoriatic arthritis (PsA) were surveyed (75% had PsO alone, 23% had PsO and PsA, and 2% had PsA alone). Self-reported body surface area (BSA) data were available for 309 Japanese patients, with the majority (80%) reporting PsO-involved BSA ≤3 palms. Current symptoms of PsO were rated as moderate or severe by 43% of Japanese patients with BSA ≤3 palms, and severe by 44% of patients with BSA 4-10 palms. PsO frequently occurred in ≥1 special areas, most commonly the scalp in 76% of Japanese patients with BSA ≤3 palms, and ≥90% of those with BSA ≥4 palms. Furthermore, musculoskeletal symptoms in 42% of patients with PsO alone were suggestive of PsA. Whereas Japanese patients with BSA ≤3 palms mainly reported receiving topical therapy alone (34%) or no treatment (32%), 64% patients with BSA 4-10 palms reported receiving systemic therapy. Overall, 21% of Japanese patients with self-perceived mild symptoms of PsO and 48% of patients with special area involvement experienced at least a moderate impact of disease on quality of life (Dermatology Life Quality Index score >5). Moreover, patients and dermatologists differed in their perceptions of determinants of PsO severity and treatment, and office visit discussions. In general, these findings from the Japanese subgroup of the UPLIFT survey demonstrated that a high proportion of patients perceived their symptoms to be moderate or severe irrespective of the level of skin involvement, suggesting a persistent unmet treatment need.

Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naïve prostate cancer: a subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, Phase 3 study.

OBJECTIVES: To evaluate the efficacy and safety of abiraterone acetate plus prednisone (AAP) plus androgen-deprivation therapy (ADT) in Japanese subgroup with newly diagnosed, metastatic hormone-naïve prostate cancer (mHNPC) from Phase 3, randomized, global LATITUDE study. METHODS: Men with mHNPC having ≥2 of 3 high-risk factors (Gleason score ≥8, ≥3 bone lesions or measurable visceral metastases) randomly received abiraterone acetate 1000-mg+ prednisone 5-mg+ADT (AAP group) or ADT+Placebos (Placebo group). Coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS). RESULTS: Of total 1199 patients in the LATITUDE study, 70 (5.8%) were Japanese (n = 35 each in the AAP and placebo group). After a median follow-up of 35.02 months (range: 2.5-42.3), median OS was not reached in both AAP group and placebo group (HR: 0.635; 95% CI, 0.152-2.659) and the median length of rPFS was not reached in the AAP group and was 22 months in the placebo group (HR:0.219; 95% CI, 0.086-0.560). The most frequently reported adverse events (>20% in either group) in the Japanese subgroup were hypertension, nasopharyngitis, weight increased, hypokalemia, hot flush, back pain, hyperglycemia, ALT and AST elevation. The incidence of Grade 3 or 4 adverse events was 65.7% (23/35) in the AAP group and 20% (7/35) in the placebo group. The efficacy and safety findings of Japanese subgroup were consistent with that of the overall study population. CONCLUSION: Treatment with AAP plus ADT has shown a positive risk-benefit balance and may serve as a new treatment option to improve the prognosis of Japanese mHNPC patients with high-risk features.

Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors.

Introduction This phase 1, open-label, multicenter, single-arm, dose-escalation study aimed to evaluate safety, pharmacokinetics (PK), and pharmacodynamics of erdafitinib (JNJ-42756493), an oral selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, and to determine the recommended phase 2 dose in Japanese patients with advanced or refractory solid tumors. Methods Three to 6 patients were enrolled into sequentially escalating dose cohorts (erdafitinib 2, 4, or 6 mg) with a daily dosing schedule of 21-day cycles or a 7 days-on/7 days-off intermittent schedule (erdafitinib 10 mg or 12 mg) of 28-day cycles. Results Nineteen patients received escalating doses of erdafitinib with a daily or intermittent schedule. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (73.7%), nausea (36.8%), stomatitis (26.3%), dysgeusia (26.3%) and dry mouth (21.1%). The maximum tolerated dose was not reached in this study. No Grade 3 or higher TEAEs, or serious TEAEs were noted and no clinically significant changes in vital signs, laboratory parameters, and electrocardiogram readings were observed. However, one case of dose-limiting toxicity in the 12 mg intermittent dosing group was observed: Grade 2 detachment of retinal pigment epithelium (bilateral) with treatment discontinuation. The maximum plasma concentrations of erdafitinib exhibited a dose-dependent increase. The median tmax ranged from 2 to 3 h after the initial dose to 2-6 h following multiple daily dosing. Based on the safety and PK data, the 10 mg 7 days-on/7 days-off regimen was determined as the recommended phase 2 dose in this study. Conclusions Erdafitinib was well tolerated in Japanese patients with advanced or refractory solid tumors. TRIAL REGISTRATION: NCT01962532.