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4273 Phase 2 Study of CPX-351 in Combination with Venetoclax in Patients with Newly Diagnosed, High Risk Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
clinical trials, Research, Combination therapy, Clinical Research, Therapies
Monday, December 11, 2023, 6:00 PM-8:00 PM

Wei-Ying Jen, MD, FRCPath, MA1*, Courtney D. DiNardo, MD, MSc1, Kelly S. Chien, MD1, Yesid Alvarado-Valero, MD2*, Lucia Masarova, MD1, Mark Brandt, BS3*, Debra Bull-Linderman, RN4*, Naval Daver, MD1, Guillermo Montalban-Bravo, MD1, Alex Bataller, MD, PhD1*, Guillermo Garcia-Manero, MD5, Ghayas C. Issa3, Amin Alousi6*, Nicholas J. Short, MD1, Farhad Ravandi, MD, MBBS1 and Tapan M. Kadia, MD1

1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
2The University of Texas M.D. Anderson Cancer Center, Houston, TX
3The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Leukemia, MD Anderson Cancer Center, Houston, TX
5University of Texas MD Anderson Cancer Center, Houston, TX
6Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX


CPX-351 is a nanoscale liposome of a fixed 5:1 molar ratio of cytarabine and daunorubicin which has improved survival of secondary acute myeloid leukemia (AML)1. Venetoclax (ven) is a BCL2 inhibitor which, in combination with azacitidine or cytarabine, has become the standard of care for elderly AML. Ven has shown synergism with chemotherapy, with high complete remission (CR) rates in newly diagnosed (ND) and relapsed / refractory (RR) AML2. In this study, we aim to assess the efficacy and safety of CPX-351 and ven (CPX-ven) in RR and ND AML.


This was a phase 2 study with a lead-in safety phase. Enrolment was allowed if the blasts were 10%. Patients (pts) age 18 with RR AML were eligible for the safety lead-in phase (LIP) or arm A. Arm B enrolled pts age 18 – 69 with ND AML. Other inclusion criteria included adequate liver, renal and cardiac function, and ECOG performance status 2. Pts with CNS involvement or prior CPX-351 were excluded. The recommend phase 2 dose was CPX-351 (daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 IV on D1, 3 and 5 of induction, and daunorubicin 22 mg/m2 IV on D1 and 3 during consolidation) combined with ven on D2-8 of each cycle. Ven was dosed at 300mg daily and reduced to 150mg or 50mg daily for pts on a moderate or strong CYP3A inhibitors, respectively.

The primary outcome measure was complete remission (CR) or CR with incomplete count recovery (CRi). Here, we report the outcomes of arm B including pts with ND AML.


14 pts were enrolled on arm B. One pt withdrew and one was too early in treatment, therefore 12 were evaluable. Baseline characteristics are shown in Table 1. The median age was 59.5 years (range, 44 – 69); Four (33.3%) were female. All 12 (100%) pts were classified as adverse risk per the 2017 European Leukemia Net Guidelines. Two (16.7%) pts had treatment for a prior non-myeloid malignancy (therapy-related AML). Eight (66.7%) had an antecedent haematological disorder (secondary AML), of whom seven had treatment (median 1 line, range 1 – 2). Four (33.3%) pts had a complex karyotype, of whom three harbored a TP53 mutation.

Nine (75.0%) pts achieved a response, including four CR (33.3%), five CRi (41.6%), and one induction mortality (8.3%) prior to disease assessment. 3/4 (75.0%) pts with complex cytogenetics (including 2/3 (66.7%) with a TP53 mutation) achieved a CR/CRi. Of the secondary AML pts with an evaluable response, 5/7 (71.4%) achieved a CR/CRi. Of the nine pts achieving CR/CRi, five (55.5%) were negative for minimal residual disease (MRD) by flow cytometry. The median number of cycles to CR/CRi was one (range 1 – 2). The median overall survival (OS) was 12.9 months (95% CI, 3.1 – not reached, NR, Figure 1). The median relapse-free survival (RFS) was 8.7 months (95% CI, 3.1 –NR). 7/9 (77.8%) of responding pts underwent an allogeneic stem cell transplant (SCT) after attaining CR/CRi.

There were 90 adverse events (AE) in 10 (83.3%) pts. 80 (88.9%) were grade 1 or 2, 10 (11.1%) were grade 3. The most common AE was gastrointestinal with seven (7.8%) occurrences. Four (33.3%) pts developed grade 3 infections; of these, one (8.3%) died. The cause of death was neutropenic septic shock due to pneumonia.


CPX-ven is a feasible option for remission induction in pts with high-risk, newly diagnosed AML. The combination produced high rates of response and MRD negativity in a cohort of pts with adverse risk features, including pts with adverse karyotype and AML following prior HMA-based treatment, allowing them to proceed with SCT. Toxicities are as expected for an intensive chemotherapy regimen. Further studies are needed to confirm the efficacy of this combination.


1. Lancet JE et al. JCO 2018; 36:2684

2. DiNardo CD et al. JCO 2021; 39:2768

Disclosures: DiNardo: Notable Labs: Honoraria; ImmuniOnc: Honoraria; Fogham: Honoraria; Astellas: Honoraria; AbbVie/Genentech: Honoraria; Servier: Honoraria; Takeda: Honoraria; Novartis: Honoraria; BMS: Honoraria; Schrödinger: Consultancy. Chien: Rigel Pharmaceuticals: Consultancy; AbbVie: Consultancy. Masarova: MorphoSys US: Membership on an entity's Board of Directors or advisory committees. Daver: AbbVie: Consultancy, Research Funding; Glycomimetics: Research Funding; Trillium: Consultancy, Research Funding; Celgene: Consultancy; Trovagene: Research Funding; Hanmi: Research Funding; Gilead: Consultancy, Research Funding; Servier: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Shattuck Labs: Consultancy; Agios: Consultancy; Novartis: Consultancy; AROG: Consultancy; FATE: Research Funding; Syndax: Consultancy; Novimmune: Research Funding; Jazz: Consultancy; Astellas: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Kite, a Gilead company: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kronos Bio: Research Funding. Montalban-Bravo: Takeda: Research Funding; Rigel: Research Funding. Garcia-Manero: AbbVie: Research Funding; Bristol Myers Squibb: Other: Medical writing support, Research Funding; Genentech: Research Funding. Issa: Astex: Research Funding; Syndax: Consultancy, Research Funding; Kura Oncology: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Merck: Research Funding; NuProbe: Consultancy, Research Funding; Celgene: Research Funding; Abbvie: Consultancy; Cullinan Oncology: Research Funding. Short: Pfizer: Consultancy; Novartis: Consultancy; Astellas: Research Funding; Amgen: Honoraria; Takeda: Consultancy, Research Funding; Stemline therapeutics: Research Funding; AstraZeneca: Consultancy. Ravandi: Celgene/BMS: Consultancy, Honoraria, Research Funding; Astex/taiho: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prelude: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Syros: Consultancy, Honoraria, Research Funding; Biomea fusion: Honoraria, Research Funding; Xencor: Research Funding; Astellas: Consultancy, Honoraria, Research Funding. Kadia: AbbVie, Amgen, Inc, Ascentage Pharma Group, Astellas Pharma Global Development, Astex, AstraZeneca, BMS, Celgene, Cellenkos Inc, Cyclacel, Delta-Fly Pharma, Inc, Genentech, Inc., Genfleet, Glycomimetics, Iterion, Janssen Research and Development: Research Funding; Biologix, Cure, Hikma Pharmaceuticals: Speakers Bureau; Genzyme: Honoraria; Astellas Pharma Global Development: Research Funding; Ascentage Pharma Group: Research Funding; BMS: Consultancy, Research Funding; Jazz Pharmaceuticals, Pfizer, Pulmotect, Inc, Regeneron Pharmaceuticals, SELLAS Life Sciences Group: Research Funding; Pinotb-Bio: Consultancy; Servier: Consultancy; Delta-Fly Pharma, Inc.: Research Funding; Daiichi Sankyo, Genentech, Inc., Genzyme, Jazz Pharmaceuticals, Liberum, Novartis, Pfizer, PinotBio, Inc, Pulmotect, Inc, Sanofi-Aventis, Servier: Consultancy; Astex: Honoraria; Genentech: Consultancy, Research Funding; Agios: Consultancy; Novartis: Consultancy; GenFleet Therapeutics: Research Funding; Cyclacel: Research Funding; Pfizer: Consultancy, Research Funding; Pulmotect, Inc.: Consultancy, Research Funding; Cellenkos Inc.: Research Funding; AstraZeneca: Research Funding; Liberum: Consultancy; Celgene: Research Funding; Cure: Speakers Bureau; Amgen, Inc.: Research Funding; Glycomimetics: Research Funding; Iterion: Research Funding; Janssen Research and Development: Research Funding; Hikma Pharmaceuticals: Speakers Bureau; Regeneron Pharmaceuticals: Research Funding; Sanofi-Aventis: Consultancy; SELLAS Life Sciences Group: Research Funding.

*signifies non-member of ASH