Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Aim: Assessment of safety and clinical activity of emavusertib in combination with ibrutinib.
Methods: This is an ongoing open-label trial (NCT03328078) of emavusertib as monotherapy and in combination with ibrutinib. Part A1- completed; dose escalation of emavusertib as monotherapy; the recommended phase 2 dose (RP2D) is 300 mg BID with continuous oral dosing (Nowakowski 2020). Part A2 - completed; dose escalation of emavusertib in combination with ibrutinib at 420 and 560 mg QD (Joffe 2022). Part B - ongoing; an expansion cohort of PCNSL patients with resistance to prior BTK inhibitors for additional safety and efficacy related to exposure: emavusertib at 100 or 200 mg BID + ibrutinib at 560 mg QD in 28-Day cycles.
Results: As of 19 July 2023, 18 heavily pretreated NHL (including five PCNSL) patients received emavusertib at 100, 200, or 300 mg BID in combination with full ibrutinib doses per label. Median age was 63.5 years (range 50-92). Median number of prior lines of anti-cancer therapies was 3 (range 1-10). Eleven of 18 patients failed prior BTK inhibitors. Median treatment duration was 95.5 days (21-587 days), suggesting acceptable safety and tolerability. No DLTs were observed at the 200 mg BID dose level, and two reversible DLTs (stomatitis and syncope) were observed at the 300 mg BID dose level. The preliminary efficacy data of 16 evaluable patients in combination with ibrutinib showed 5 CRs (2 MCL, 3 PCNSL) and 1 PR (1 CLL). All 3 PCNSL patients with CR were previously treated with BTK inhibitors.
Conclusion: The combination of emavusertib plus ibrutinib (ema+ibr) is well tolerated with an acceptable long-term safety profile and promising efficacy, showing several objective responses in heavily pretreated and/or BTK inhibitor resistant patients. Emavusertib may have the potential to overcome BTK inhibitor resistance and the combination of ema+ibr has the potential to show increased anti-cancer activity compared to ibrutinib monotherapy.
Disclosures: Grommes: BTG International: Other: Provision of services; Ono Pharma: Other: Provision of services; Roche: Other: Provision of services. Lunning: Astellas: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Caribou: Consultancy, Honoraria; CRISPR: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; EUSA: Consultancy, Honoraria; Fate Therapeutics: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; InstilBio: Consultancy, Honoraria; Ipsen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Loxo: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Nurix: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; SeaGen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Curis: Research Funding; Astra Zeneca: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Isufi: Incyte: Consultancy; Abbvie: Consultancy; Genmab: Consultancy; Gilead: Consultancy, Current equity holder in publicly-traded company; ADC Therapeutics: Consultancy; Beam Therpauetics: Consultancy. Leslie: CLL: Other: Educational role; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genmab: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Eli Lilly: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; LRF: Other: Educational role; Kite, a Gilead Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Janssen/ J&J: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Other: Travel support, Speakers Bureau; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; SeaGen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/ Bristol Myers Squibb: Other: Travel support, Speakers Bureau; Janssen/PCYC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; LLS: Other: Educational role/ Leadership role in LLS light the night events (unpaid). Nowakowski: Genentech: Consultancy; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Blueprint Medicines: Consultancy; Kymera Therapeutics: Consultancy; Fate Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Curis: Consultancy; Celgene Corporation: Consultancy; TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Debiopharm: Consultancy; Karyopharm Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Selvita Inc: Consultancy; Seagen: Consultancy; Ryvu Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; F Hoffmann-La Roche Limited: Consultancy; Zai Lab Limited: Consultancy; Bantam Pharmaceutical LLC: Consultancy; Kite Pharma: Consultancy; MEI Pharma: Consultancy; Incyte: Consultancy; MorphoSys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
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