Type: Oral
Session: 626. Aggressive Lymphomas Prospective Therapeutic Trials: Challenging Populations
Hematology Disease Topics & Pathways:
Adults, Lymphomas, Non-Hodgkin Lymphoma, T Cell Lymphoma, Diseases, Lymphoid Malignancies, Study Population
Aims: This multicenter, single-arm, open-label, phase 2 study (NCT04102150) evaluated the efficacy and safety of single-agent valemetostat in pts with R/R ATL. The primary objective was to evaluate efficacy by central efficacy assessment committee (EAC)–assessed overall response rate (ORR), defined as the proportion of pts whose best response was complete remission (CR), uncertified CR, or partial remission using international consensus criteria (J Clin Oncol. 2009;27:453-59). The null hypothesis was an ORR of ≤5% (binomial test with a 1-sided significance level of 5%). Secondary outcome measures included CR rate, duration of response (DOR) per EAC, efficacy per investigator (INV) assessment, and the safety and pharmacokinetics of valemetostat.
Methods: Pts ≥20 years of age with R/R ATL (acute, lymphomatous, or unfavorable chronic type) were enrolled from 24 sites in Japan. Pts must have had a positive antihuman T-cell leukemia virus type 1 antibody serum test and received prior therapy with mogamulizumab or ≥1 prior systemic therapy in the case of intolerance of, or contraindication for, mogamulizumab. Pts with prior allogeneic hematopoietic stem cell transplant were excluded. Valemetostat 200 mg was orally administered once daily in continuous 28-day cycles until disease progression or intolerance. The EAC-determined efficacy assessment was based on central evaluation of radiographic images and clinical data, including peripheral blood, skin, and bone marrow lesions (J Clin Oncol. 2009;27:453-59).
Results: At the time of data cutoff (April 24, 2021), the study enrolled the planned 25 pts which included 16, 6, and 3 pts with acute, lymphomatous, or unfavorable chronic ATL subtypes, respectively. The median age was 69 years (range, 59-84 years). The median number of prior lines of therapy was 3 (range, 1-8). 24 pts (96.0%) had prior treatment with mogamulizumab.
The study met its primary endpoint: with a median follow-up of 28 weeks (range, 14-71 weeks), valemetostat resulted in a 48% (12/25) ORR per EAC assessment (P<.0001; 95% CI, 27.8%-68.7%), including a 20% CR rate. Primary efficacy data are summarized in the Table. The median DOR (n=12) was not reached (95% CI, 8.14 weeks-not reached). EAC- and INV-assessed results were similar.
8 of 25 pts (32%) remained on treatment. 25 pts (100%) experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs occurred in 15 pts (60%), and grade ≥3 serious TEAEs occurred in 6 pts (24%); valemetostat was not associated with any deaths. Dose interruption or reduction due to TEAEs occurred in 5 (20%) and 2 (8%) pts, respectively. Two pts (8%) discontinued due to TEAEs. The most common TEAEs (≥30% of pts) were platelet count decreased (80%), dysgeusia (36%), anemia (48%), and alopecia (40%); grade ≥4 platelet count decreased occurred in 3 pts (12%).
Summary/Conclusions: Valemetostat resulted in a high response rate and durable antitumor effect in Japanese pts with R/R ATL, the majority of whom were pretreated with mogamulizumab. Valemetostat’s safety profile was manageable. These results are consistent with those observed in the phase 1 study conducted in Japan and the US, suggesting that valemetostat could be a new treatment option for pts with R/R ATL. Valemetostat is also being evaluated in a global phase 2 study in pts with R/R ATL and R/R peripheral T-cell lymphoma (NCT04703192).
Disclosures: Yoshimitsu: Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Izutsu: Kyowa Kirin: Honoraria, Research Funding; Incyte: Research Funding; Chugai: Honoraria, Research Funding; Bayer: Research Funding; Beigene: Research Funding; AstraZeneca: Honoraria, Research Funding; Yakult: Research Funding; AbbVie: Honoraria, Research Funding; Takeda Pharmaceutical: Honoraria, Research Funding; HUYA Bioscience International: Research Funding; Eisai: Honoraria, Research Funding; MSD: Research Funding; Janssen: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Pfizer: Research Funding; Symbio: Honoraria, Research Funding; Allergan Japan: Honoraria; FUJI FILM Toyama Chemical: Honoraria. Makita: Takeda: Consultancy, Honoraria; SymBio: Honoraria; Novartis: Honoraria; Eisai: Honoraria; Daiichi-Sankyo: Consultancy; CSL Behring: Honoraria; Chugai: Honoraria; BMS: Consultancy, Honoraria. Nosaka: Eisai Co., Ltd: Honoraria; Celgene K.K.: Honoraria; Kyowa Kirin Co., Ltd: Consultancy, Honoraria, Research Funding; Meiji Seika Parma Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Research Funding; Janssen Pharmaceutical K.K.: Honoraria; Bristol Myers Squibb: Honoraria. Utsunomiya: Novartis Pharma: Honoraria; Kyowa Kirin: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Janssen Pharmaceutical: Honoraria; JIMRO: Honoraria; Meiji Seika Pharma: Honoraria; Otsuka Medical Devices: Honoraria. Kusumoto: Daiichi Sankyo: Research Funding; Chugai: Honoraria, Research Funding; Kyowa Kirin: Honoraria. Tsukasaki: Solasia Pharma: Consultancy; Meiji Seika Pharma: Consultancy; Yakuruto: Consultancy; HUYABIO: Consultancy, Research Funding; Ono Pharma: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Takeda: Honoraria; Kyowa-hakko/Kirin: Honoraria, Research Funding; Eizai: Honoraria, Research Funding; Byer: Research Funding; Chugai Pharma: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Ono: Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Eisai Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; DAIICHI SANKYO COMPANY, LIMITED.: Honoraria; Mundipharma K.K.: Honoraria; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding; Astellas Pharma Inc.: Honoraria; Bristol-Myers Squibb Company: Honoraria; Novartis Pharma KK: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; Takeda Pharmaceutical Company Limited.: Honoraria; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Rai: Janssen Pharmaceutical: Speakers Bureau; ONO Pharmaceutical Co., Ltd: Speakers Bureau; Chugai Pharmaceutical Co., Ltd: Speakers Bureau; Eisai Co., Ltd: Speakers Bureau. Yamada: Daiichi Sankyo: Current Employment. Kato: Bristol Myers Squibb: Current equity holder in publicly-traded company; Daiichi Sankyo: Current Employment. Tachibana: Daiichi Sankyo: Current Employment. Kakurai: Daiichi Sankyo: Current Employment. Adachi: Daiichi Sankyo: Current Employment. Tobinai: Celgene: Consultancy, Honoraria; Chugai Pharmaceutical: Honoraria; Eisai: Honoraria; Daiichi Sankyo: Consultancy, Honoraria; HUYA Bioscience International: Consultancy, Honoraria; Kyowa Kirin: Honoraria; Mundipharma: Consultancy, Honoraria; Ono Pharmaceutical: Consultancy, Honoraria; Solasia Pharma: Honoraria; Takeda Pharmaceutical: Consultancy, Honoraria; Yakult: Honoraria; Zenyaku Kogyo: Consultancy, Honoraria. Yonekura: AbbVie: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Daiichi Sankyo: Honoraria; Eisai: Honoraria; Eli Lilly Japan: Honoraria; Janssen Pharmaceuticals: Honoraria; Kaken Pharmaceutical: Honoraria; Kyowa Kirin: Honoraria; Maruho: Honoraria; Minophagen Pharmaceutical: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; Taiho Pharmaceutical: Honoraria; Torii Pharmaceutical: Honoraria; UCB Japan: Honoraria. Ishitsuka: Pfizer: Other: Personal fees; Astellas Pharma: Other: Personal fees, Research Funding; Genzyme: Other: Personal fees; Sumitomo Dainippon Pharma: Other: Personal fees, Research Funding; Eisai: Other: Personal fees, Research Funding; Novartis: Other: Personal fees; Janssen Pharmaceuticals: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Mundipharma: Other: Personal fees; Takeda: Other: Personal fees, Research Funding; BMS: Other; Chugai Pharmaceutical: Honoraria, Other: Personal fees, Research Funding; Celgene: Honoraria, Other: Personal fees; Ono Pharmaceutical: Other: Personal fees, Research Funding; Kyowa Kirin: Other: Personal fees, Research Funding; Daiichi Sankyo: Consultancy, Other: Personal fees; Mochida: Other: Personal fees, Research Funding; Shire: Other; Otsuka Pharmaceutical: Other: Personal fees; Teijin Pharma: Research Funding; MSD: Research Funding; Asahi kasei: Research Funding; Eli Lilly: Research Funding; Huya Japan: Other: Personal fees.
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