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2098 Results of Cynk-001-AML-001: A Phase I Multi-Dose Study Evaluating the Safety, Tolerability, and Persistence of Cynk-001 in Adults with De Novo or Secondary Acute Myeloid Leukemia in Morphologic Complete Remission with Minimal Residual Disease or Relapsed/Refractory AML

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, AML, Clinical Research, drug development, Diseases, Therapies, Adverse Events, Myeloid Malignancies, Minimal Residual Disease
Saturday, December 9, 2023, 5:30 PM-7:30 PM

James McCloskey, MD1, Hongtao Liu, MD, PhD2, Daniel N. Egan, MD3, Jesus G. Berdeja, MD4, Stephanie B. Tsai, MD, MS5, Adrian Kilcoyne, MD6*, Cherie Daly7*, Sharmila Koppisetti8*, Ramji Krishnan, PhD9*, Robert Hariri, MD, PhD10* and Eunice S Wang, MD11

1The John Theurer Cancer Center at Hackensack Meridian Health, Hackensack, NJ
2University of Wisconsin-Madison, Madison, WI
3Swedish Center for Blood Disorders and Stem Cell Transplants, Seattle, WA
4Sarah Cannon Center For Blood Cancers, Nashville, TN
5Loyola University Health System, Maywood, IL
6Celularity, Florham Park, NJ
7Celularity Inc, Warren, NJ
8Celularity Inc., Florham Park, NJ
9Celularity, Florham Park
10Celularity, florham park, NJ
11Department of Medicine, Roswell Park Comprehensive Cancer Center, BUFFALO, NY

Introduction: Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease often with suboptimal outcomes. While progress has been achieved in the treatment of AML, relapse remains a significant challenge. Novel therapeutic options aimed at attaining minimal residual disease (MRD) negative complete remission (CR) are expected to reduce the incidence of relapse and prolong survival. Evidence shows that natural killer (NK) cells can exhibit potent anti-leukemia activity against AML. CYNK-001 is a CD56+CD3- enriched, off-the-shelf, unmodified allogeneic NK cells expanded from placental CD34+ cells.

Aim CYNK-001-AML-001 is a phase I multi-dose study evaluating the safety, tolerability, and persistence of CYNK-001 with or without recombinant human interleukin-2 (rhIL-2) in adults with de novo or secondary acute myeloid leukemia (AML) in morphologic complete remission (CR) with minimal residual disease (MRD) or relapsed/refractory (R/R) AML.

Methods This Phase I, single-arm, dose escalation clinical trial (NCT04310592) enrolled patients 18-80 years with R/R AML or patient in MRD positive CR. Two lymphodepletion regimens were assessed. Patients in cohorts 1-3 underwent standard lymphodepletion with fludarabine (25 mg/m2/day) and cyclophosphamide (300 mg/m2/day) on days -5, -4 and -3. Subsequent cohorts received enhanced lymphodepletion with fludarabine (30 mg/m2/day) and cyclophosphamide (900 mg/m2/day) on days -6, -5, -4 and -3. Escalating doses of NK cells were administered following a standard 3+3 design, with 2 separate arms (MRD+ arm and R/R arm) starting with cohort 4. A starting dose of 600 million cells on days 0, 7, and 14 was escalated to a maximum dose of 1.8 billion cells on days 0, 7, 14 and 21. The primary objective of the study was to determine the maximum tolerated dose (MTD) or maximum planned dose (MPD) of CYNK-001 and to assess the safety of multiple infusions of CYNK-001 administered using a flat, non-weight-based dose as assessed by the frequency and severity of adverse events (AE). The secondary objective was to assess the clinical efficacy of CYNK-001 in AML subjects.

Results 28 patients (17 with R/R AML and 11 with MRD-positive AML) were enrolled during dose escalation, and 27 received CYNK-001. The highest dose of NK cells administered was 1.8 billion cells X 4 in cohort 6b (patients with R/R AML). Treatment was well tolerated with no dose limiting toxicities (DLTs) even at the highest dose. No cases of neurotoxicity or GvHD were reported. Four cases of grade 2 CRS were reported but there were no cases of ≥ grade 3 CRS. Two incidences of grade 4 thrombocytopenia and one grade 4 decreased white blood cell count were noted in patients who had received enhanced lymphodepletion. In R/R AML patients treated with the highest dose of CYNK-001, 2 of 4 patients achieved an objective response of Morphologic Leukemia-Free State (MLFS) on Day 28. One of these patients has maintained a response to D120 and is continuing follow up. One of 3 patients with MRD +ve AML treated with 3 doses of 1.8 billion CYNK-001 cells per dose achieved MRD negativity until day 120 at which time a blast count of 1.6% was observed.

Conclusion Treatment with CYNK-001 showed biological activity as evidenced by achievement of MLFS in R/R AML patients and eradication of AML MRD positivity in AML patients in morphologic CR. Therapy was generally well-tolerated, with no dose-limiting toxicities observed with even the highest dose of CYNK-001. This trial yielded important insights into the optimal approach to lymphodepletion and the potential clinical efficacy of allogeneic NK cells in R/R AML. Based on these results, this trial is now closed to further enrollment and future development activities will focus on next generation NK cell therapies edited to optimize persistence and efficacy and limit the requirement for enhanced lymphodepletion.

Disclosures: McCloskey: Jazz Pharmaceuticals: Speakers Bureau; Novartis: Consultancy; Amgen: Speakers Bureau; Bristol-Myers Squibb/Pfizer: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Speakers Bureau; BluePrint Health: Speakers Bureau; Incyte: Speakers Bureau; Blueprint Medicines: Consultancy; Takeda: Speakers Bureau; BluPrint Oncology: Honoraria. Liu: Astellas: Research Funding; Rigel: Consultancy; Servier: Consultancy; CTI Biopharm: Consultancy; Nkarta: Research Funding; Nkarta: Consultancy; Miltenyi Biotec: Research Funding; Alexion: Research Funding; Pfizer: Consultancy; Agios: Consultancy. Berdeja: Janssen: Consultancy, Research Funding, Speakers Bureau; Incyte: Research Funding; Sanofi: Research Funding; Takeda: Consultancy, Research Funding; Roche: Consultancy; Genentech: Research Funding; GSK: Research Funding; Ichnos Sciences: Research Funding; Poseida: Research Funding; Novartis: Research Funding; Teva: Research Funding; Karyopharm: Research Funding; Kite Pharma: Consultancy; Legend Biotech: Consultancy; Lilly: Research Funding; Fate Therapeutics: Research Funding; EMD Serono: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Celularity: Research Funding; Cartesian: Research Funding; CARsgen: Research Funding; C4 Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Amgen: Research Funding; AbbVie: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Acetylon: Research Funding; 2seventy bio: Consultancy, Research Funding. Tsai: Bristol Myers Squibb: Speakers Bureau; Jazz Pharmaceutical: Speakers Bureau. Kilcoyne: celularity: Current Employment, Current equity holder in publicly-traded company. Daly: celularity: Ended employment in the past 24 months. Koppisetti: celularity: Current Employment. Krishnan: Celularity: Current Employment. Hariri: celularity: Current Employment, Current equity holder in publicly-traded company. Wang: Sumitomo: Consultancy; Astellas: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy; CTI Biopharma: Consultancy; Daiichi Sankyo: Consultancy; Gilead: Consultancy; Glaxo Smith Kline: Consultancy; Janssen: Consultancy; Jazz: Consultancy; Johnson and Johnson: Consultancy; Kite: Consultancy; Kura Oncology: Consultancy; Novartis: Consultancy, Speakers Bureau; NuProbe: Consultancy; Pfizer: Consultancy, Speakers Bureau; PharmaEssentia: Consultancy; Rigel: Consultancy; Sellas: Consultancy; Abbvie: Consultancy; Amgen: Consultancy.

*signifies non-member of ASH