Type: Oral
Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Relapsed/Refractory AML
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, AML, adult, Clinical Research, Combination therapy, Diseases, Therapies, Myeloid Malignancies, Study Population, Human
METHODS: In this phase 1b/2 study, eligible patients with CD123-positive R/R AML received PVEK+AZA+VEN in a three-drug escalation over a 28-day cycle: PVEK 0.015 or 0.045 mg/kg day 7, AZA 50 or 75 mg/m2 days 1-7, and VEN 400 mg (or equivalent with azole) for 8, 14, or 21 days. The higher intensity cohorts are defined as patients treated with PVEK on day 7, and either a PVEK dose at 0.045mg/kg or at least 14 days of VEN. Enrollment of relapsed and frontline patients is ongoing in the expansion cohorts of PVEK 0.045 mg/kg day 7, AZA 75 mg/m2 days 1-7, and VEN 400 mg for at least 14 days.
Responses were determined using ELN 2017 criteria (with the addition of CRh and CRp) and a 14-day count recovery window.
RESULTS: As of June 20, 2022, preliminary safety data are available for 71 patients with R/R AML treated in the higher-intensity cohorts as defined above. The median age was 68 years (range, 25-82), 30% had secondary AML, 32% had primary refractory disease, 44% had received prior VEN, 25% had prior allogeneic stem cell transplant, and 54% of the patients were ELN 2017 adverse risk. Fifty-two percent of the patients had received ≥ 2 prior lines of therapy.
The most common treatment-emergent adverse events (TEAE) (all grades [grade 3+ events]) seen in >20% of patients were febrile neutropenia (30% [24%]) and infusion-related reactions (IRRs, 21% [3%]). Pneumonia was reported in 16% of patients [grade 3+ 11%]. Overall, 10% of patients discontinued PVEK due to a TEAE (mostly unrelated to PVEK). Cytopenias and infections were consistent with those observed with HMA+VEN in patients with R/R AML. 30-day mortality was 3%.
Response data were available for 61 patients with R/R AML. The objective response rate (ORR [CR, CRh, CRp, CRi, MLFS) was 51% with a composite complete remission (CCR [CR, CRh, CRp, CRi]) rate of 31%. VEN-naïve patients had an ORR and CCR of 62% and 47% compared with 37% and 11%, respectively, in patients who had prior VEN exposure. Of note, responses were observed in 9 of 11 patients with FLT3-ITD AML with an ORR of 82% and a CCR of 64%. Table 1 displays response data from sub-groups of interest. Additionally, maximum best change in bone marrow blasts is depicted in Figure 1.
CONCLUSION: With a manageable safety profile in patients with R/R AML, the higher-intensity cohorts of the novel PVEK triplet demonstrated anti-leukemia activity across several difficult-to-treat subsets of patients. Enrollment and follow-up in both relapsed and frontline patients are ongoing (NCT04086264). Additional and updated safety and efficacy data will be presented at ASH.
Disclosures: Daver: Agios, Celgene, SOBI and STAR Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kartos and Jazz Pharmaceuticals: Other: Data monitoring committee member; Karyopham Therapeutics and Newave Pharmaceutical: Research Funding; Astellas, AbbVie, Genentech, Daiichi-Sankyo, Novartis, Jazz, Amgen, Servier, Karyopharm, Trovagene, Trillium, Syndax, Gilead, Pfizer, Bristol Myers Squibb, Kite, Actinium, Arog, Immunogen, Arcellx, and Shattuck: Consultancy, Other: Advisory Role; Astellas, AbbVie, Genentech, Daiichi-Sankyo, Gilead, Immunogen, Pfizer, Bristol Myers Squibb, Trovagene, Servier, Novimmune, Incyte, Hanmi, Fate, Amgen, Kite, Novartis, Astex, KAHR, Shattuck, Sobi, Glycomimetics, Trillium: Research Funding. Montesinos: Menarini/Stemline: Consultancy, Research Funding; Gilead: Consultancy, Speakers Bureau; Otsuka: Consultancy; Kura Oncology: Consultancy; ABBVIE: Consultancy, Research Funding, Speakers Bureau; BMS: Research Funding; Novartis: Research Funding; Jazz Pharma: Consultancy, Research Funding, Speakers Bureau; Beigene: Consultancy; Astellas: Consultancy, Speakers Bureau; Incyte: Consultancy; Takeda: Consultancy, Research Funding; Ryvu: Consultancy. Aribi: SeaGen: Consultancy. Marconi: menarini/stemline: Honoraria, Speakers Bureau; astellas: Honoraria; servier: Honoraria; pfizer: Honoraria, Research Funding, Speakers Bureau; abbvie: Research Funding. Altman: Fujifilm: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Glycomimetics: Other: Data Monitoring Committee; Kartos Therapeutics: Research Funding; Amgen: Research Funding; Aptos: Research Funding; Aprea: Research Funding; Syros: Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Research Funding; Biosight: Membership on an entity's Board of Directors or advisory committees, Other: reumbursement for travel, Research Funding; Abbvie: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; ALX Oncology Inc: Research Funding; Kura Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Research Funding. Wang: Kura Oncology: Consultancy, Honoraria, Other: Advisory Board, Steering Committee, Speakers Bureau; Abbvie: Consultancy, Honoraria, Other: member of data monitoring committee ; Mana Therapeutics: Consultancy, Honoraria; Rafael Pharmaceuticals: Other: Data Safety Monitoring Committee; Gilead: Consultancy, Honoraria, Other: Advisory Board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory Board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory Board; Macrogenics: Consultancy; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Astellas: Consultancy, Honoraria; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Other: Advisory Board; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Genentech: Consultancy; Takeda: Consultancy, Honoraria, Other: Advisory Board; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Dava Oncology: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board. Roboz: Celgene: Consultancy, Other: travel and accommodation expenses, Research Funding; Amgen: Consultancy; Celltrion: Consultancy, Other: Travel and accommodation expenses; Otsuka: Consultancy; Actinium: Consultancy; GlaxoSmithKline: Consultancy; Bristol Myers Squibb: Consultancy; Roche: Consultancy; Mesoblast: Consultancy; Helsinn Therapeutics: Consultancy; Clovis Oncology: Other: Travel and accommodation expenses; Amgen: Consultancy, Other: travel; Agios: Consultancy, Research Funding; Jazz: Consultancy, Other: travel; Astex Pharmaceuticals: Consultancy, Other: Travel and Accommodation expenses, Research Funding; Jasper Therapeutics: Consultancy; MedImmune: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Other: Travel and accommodation expenses; Bayer: Consultancy, Other: Travel and accommodation expenses; Genentech/Roche: Consultancy, Other: Travel and accommodation expenses; Karyopharm Therapeutics: Research Funding; AbbVie: Consultancy, Other: travel and accommodations, Research Funding; Astellas: Consultancy; MEI Pharma: Consultancy, Research Funding; Sandoz: Consultancy, Other: Travel and accommodation expenses; Amphivena Therapeutics: Other: Travel and accommodation expenses, Research Funding; Array BioPharma: Other: Travel and accommodation expenses; CTI: Research Funding; Sunesis Pharmaceuticals: Other: Travel and accommodation expenses, Research Funding; Eisai: Other: Travel and accommodation expenses; Novartis: Consultancy, Other: Travel and accommodation expenses, Research Funding; Takeda: Consultancy; Daiichi Sankyo: Consultancy; Mofitt Cancer Center: Research Funding; Janssen: Consultancy, Other: travel and accommodation expenses, Research Funding; Bristol Myers Squibb: Consultancy; Agios: Other: travel, Research Funding; Onconova Therapeutics: Research Funding; Tensha Therapeutics: Research Funding. Gaidano: Astra-Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Walter: AbbVie: Consultancy; Stemline Therapeutics: Research Funding; Selvita: Research Funding; Race Oncology LTD: Consultancy; Pfizer, Inc: Consultancy, Research Funding; New Link Genetics: Consultancy; Kite Pharma, Inc: Consultancy; Kronos Bio, Inc: Consultancy; Kura Oncology: Consultancy, Research Funding; MacroGenics: Consultancy, Research Funding; ImmunoGen: Research Funding; Janssen Global Services, LLC: Consultancy; Janssen Research and Development: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; BerGenBio, ASA: Consultancy; Boston Biomedical, Inc: Consultancy; BioLineRx, LTd: Consultancy, Research Funding; Aptevo Therapeutics: Consultancy, Research Funding; Astellas Pharma US, Inc: Consultancy; Arog Pharmaceuticals: Research Funding; Bristol Myers Squibb, Inc: Consultancy; GSK: Consultancy; Genentech: Consultancy; Celgene, Inc: Consultancy, Research Funding; Amphivena Therapeutics, Inc: Current equity holder in publicly-traded company; Amgen: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Orum Therapeutics, Inc.: Consultancy. Jeyakumar: Pfizer: Research Funding; Jazz Pharmaceuticals: Research Funding. DeAngelo: Abbvie: Research Funding; Blueprint Medicines Corporation: Consultancy; Incyte: Consultancy; Forty-Seven: Consultancy; Autolus: Consultancy; Agios: Consultancy; Amgen: Consultancy; Glycomimetics: Research Funding; Shire: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Jazz Pharmaceuticals: Consultancy. Erba: Incyte: Consultancy, Speakers Bureau; ImmunoGen: Consultancy, Research Funding; Glycomimetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; MacroGenics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Covance (Abbvie): Consultancy, Other: Independent Review Committee, Research Funding; Janssen Oncology: Consultancy; Trillium Therapeutics: Consultancy; Takeda: Consultancy; Kura Oncology: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Gilead/Forty Seven: Research Funding; PTC therapeutics: Research Funding; ALX Oncology: Research Funding; Pfizer: Consultancy; Daiichi Sankyo: Consultancy, Research Funding; Celgene: Consultancy, Other, Speakers Bureau; Astellas Pharma: Consultancy; Amgen: Consultancy, Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Todisco: Jazz Pharmacueticals: Consultancy, Other: Advisory Board; Abbvie: Consultancy, Other: Advisory Board; Janssen: Consultancy, Other: Advisory Board. Begna: ImmunoGen: Research Funding; Novartis: Honoraria. Advani: Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunogen: Research Funding; OBI: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gastaud: Abbvie: Consultancy; Celgene/BMS: Consultancy; Pfizer: Consultancy; GSK: Consultancy. De La Fuente: Celgene: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Speakers Bureau. Curti: Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Membership on an entity's Board of Directors or advisory committees. Vyas: Pfizer: Honoraria; Celgene: Honoraria, Research Funding; JAZZ: Honoraria; Abbvie: Honoraria; Astellas: Honoraria; Bristol Myers Squibb: Research Funding; Daiichi Sankyo: Honoraria. Boissel: GILEAD: Honoraria; AMGEN: Honoraria; ARIAD/INCYTE: Honoraria; ASTELLAS: Honoraria; NOVARTIS: Honoraria; SERVIER: Honoraria. Vey: BMS: Honoraria; Novartis: Honoraria, Research Funding; Roche: Honoraria; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria. Recher: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Macrogenics: Honoraria, Membership on an entity's Board of Directors or advisory committees; MaatPharma: Research Funding; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Incyte: Honoraria; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Platzbecker: Jazz: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Geron: Honoraria; BMS/Celgene: Honoraria; Silence Therapeutics: Honoraria; Abbvie: Honoraria. Kapp-Schwoerer: Pfizer Inc.: Consultancy; AbbVie Inc.: Consultancy, Honoraria, Other: Travel support; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Travel support. Schliemann: Boehringer-Ingelheim: Research Funding; Astrazeneca: Consultancy; Astellas: Consultancy; Abbvie: Consultancy, Other: travel grants; Philogen S.p.A.: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Other: travel grants; Jazz: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Konopleva: Kisoji: Consultancy, Honoraria; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Reata Pharmaceuticals: Current equity holder in private company, Patents & Royalties; Eli Lilly: Consultancy, Patents & Royalties, Research Funding; Cellectis: Consultancy, Other: Grant support, Research Funding; Calithera: Other: Grant Support, Research Funding; Ablynx: Other: Grant support, Research Funding; Agios: Other: grant support, Research Funding; Ascentage: Other: grant support, Research Funding; AstraZeneca: Other: grant support, Research Funding; Rafael Pharmaceutical: Other: grant support, Research Funding; Sanofi: Other: grant support, Research Funding; Novartis: Patents & Royalties, Research Funding; Amgen: Consultancy; Forty-Seven: Consultancy, Honoraria, Other: Grant support; Stemline Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grant support, Research Funding; Genentech: Consultancy, Other: grant support, Research Funding; AbbVie: Consultancy, Other: grant support, Research Funding. Sallman: Aprea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Nemucore: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Agios: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees; Lixte: Patents & Royalties: LB-100; Kite: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta: Consultancy; Syntrix Pharmaceuticals: Research Funding. Marcucci: Agios: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings; Abbvie: Other: Speaker and advisory scientific board meetings. Pemmaraju: Roche Diagnostics: Honoraria; LFB Biotechnologies: Honoraria; SagerStrong Foundation: Research Funding; Plexxikon: Research Funding; Affymetrix: Research Funding; Cellectis: Research Funding; Daiichi Sankyo: Research Funding; Samus Therapeutics: Research Funding; Pacylex Pharmaceuticals: Consultancy; Novartis: Honoraria, Research Funding; Incyte: Research Funding; MustangBio: Honoraria; AbbVie: Honoraria, Research Funding; Stemline Therapeutics: Honoraria, Research Funding. Martinelli: Incyte: Consultancy; Astellas: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy; Roche: Consultancy; Daiichi Sankyo: Consultancy; Stemline: Consultancy; Abbvie: Consultancy; Celgene/BMS: Consultancy, Speakers Bureau. Kantarjian: Ipsen Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Research Funding; Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Consultancy, Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas Health: Honoraria, Membership on an entity's Board of Directors or advisory committees; NOVA Research: Honoraria; Amgen: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; KAHR Medical Ltd: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Research Funding; Takeda: Honoraria. Sloss: ImmunoGen: Current Employment. Malcolm: ImmunoGen: Current Employment. Zweidler-McKay: ImmunoGen, Inc.: Current Employment. Sweet: berGenBio: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mablytics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; AROG: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Syntrix Pharmaceuticals: Research Funding.