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We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti‐CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single‐arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14. Subsequently, cusatuzumab was administered intravenously on days 3 and 17 at 20 mg/kg in combination with azacitidine (75 mg/m2) on days 1‐7 of each 28‐day cycle. All six participants had at least one treatment‐emergent adverse event, and the most common treatment‐emergent adverse events (all grades) were leukopenia (four participants [66.7%]) and constipation (three participants [50.0%]). No dose‐limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants, and further exploration of this combination is warranted. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration‐sensitive prostate cancer from the phase 3, randomized, global TITAN study. Methods: Men with metastatic castration‐sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression‐free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal‐related events. Safety was also assessed. Results: Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression‐free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205–2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210–3.361; P = 0.805). In the interim analysis, the median radiographic progression‐free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. Conclusions: The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration‐sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. Poor prognosis has been shown in patients with cGVHD after the failure of primary steroid-based treatments. A previous report demonstrated the efficacy and safety of ibrutinib in these patients, leading to the approval of ibrutinib for cGVHD in Japan. Here, we report the extended follow-up of patients in this study., Objectives: To evaluate the safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD., Study Design: An open-label, single-arm, multicenter study of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD (NCT No.: NCT03474679; Clinical Registry No.: CR108443)., Results: At the time of the final data cutoff, 7/19 (36.8%) patients completed the study treatment, and 12/19 (63.2%) patients discontinued ibrutinib. After a median follow-up of 31.11 months (range:1.9 to 38.6 months), the best overall response rate was 84.2% (16/19 patients; 95% CI:60.4%, 96.6%) in all treated populations, with a median time to response of 2.81 (range:1.0 to 27.6) months. Of 15 responders with ≥2 organs involved at baseline, seven (46.7%) had responses in multiple organs. An improvement in the organ response rate was observed for the skin, eye, mouth, and esophagus compared with that in a previous report. The rate of sustained response for ≥20 weeks, ≥32 weeks, and ≥44 weeks were 68.8%, 62.5%, and 50.0%, respectively for 16 responders. The median daily corticosteroid dose requirement tended to decrease over time for all treated analysis sets. Twelve of 19 patients (63.2%) reached a corticosteroid dose of <0.15 mg/kg/day for at least one week, and four (21.1%) discontinued corticosteroid treatment for at least 28 days during the study. The failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively. The safety findings of this updated analysis were consistent with the safety profile observed at the time of the primary analysis and the known ibrutinib safety profile. Common grade ≥3 treatment-emergent adverse events (TEAEs) were pneumonia (6/19 [31.6%] patients), platelet count decreased, and cellulitis (3/19 [15.8%] patients each). After the primary analysis, no new TEAEs leading to death, treatment discontinuation, or dose reduction were reported, and no new patients reported major hemorrhage. Cardiac arrhythmia (Grade 2 atrial flutter) was reported in 1/19 (5.3%) patients. No new safety signs were observed despite prolonged ibrutinib exposure., Conclusions: The final results support previous conclusions, demonstrating a clinically meaningful response and acceptable safety profile of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.T. received payment or honoraria from Janssen Pharmaceutical, Sanofi, Takeda Pharmaceutical Co., Nippon Shinyaku Co., Beckman Coulter Inc., Novo Nordisk Pharma., Daiichi Sankyo Co., Chugai Pharmaceutical Co., Asahi Kasei Pharma Corp., and Sumitomo Dainippon Pharma Co. for lectures, presentations, speakers' bureaus, manuscript writing, or educational events. M.S. received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Kyowa Kirin Co. Ltd., Chugai, Pfizer, Astellas, Nippon-Shinyaku, Ono, MSD, Bristol-Myers-Squibb, Asahi Kasei, Novartis, Eisai, Otsuka, Sumitomo-Dainippon, Sanofi, Takeda, Celgene, Mochida, Shire, Mundipharma, abbvie, CSL Behring, Sym-Bio, Janssen, AstraZeneca, DAIICHI SANKYO, and GlaxoSmithKline. N.D. received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing, or educational events from Novartis Pharma and Janssen Pharma. Y.U. participated in a Data Safety Monitoring Board or Advisory Board with Sanofi and Otsuka Pharmaceutical. M.O. received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Otsuka Pharmaceutical Co. Ltd. N.Y. is an employee of Janssen Pharmaceutical K.K. and holds stock ownership with Johnson & Johnson. T.H. and E.F. are employees of Janssen Pharmaceutical K.K. S.S., T.O., T.I., and T.K. declare no conflict of interest. Disclosure forms provided by the authors are available on the website., (Copyright Ⓒ2023 Asia-Pacific Blood and Marrow Transplantation Group (APBMT).)