Axatilimab + CAR-T for High-Risk Lymphoma

An Open-label, Phase I Trial, With an Expansion Cohort: Macrophage Conditioning to Synergize With CAR-T in High-risk Lymphoma (MAC-SHIFT)

Axatilimab + CAR-T in High-Risk Lymphoma

Study Overview

• Status: Not yet recruiting
• Conditions: High-Grade B-Cell Lymphoma, Nos; Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma; Diffuse Large B Cell Lymphoma (DLBCL); Follicular Grade 3 Lymphoma; High-grade B-cell Lymphoma (HGBCL); PMBCL
• Intervention / Treatment: Drug: Axatilimab

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Caitlin Guzowski, MBA, MHA, CCRC; Phone Number: 404-851-8523; Email: caitlin.guzowski@northside.com
• Study Contact Backup: Name: Joseph Maakaron, MD; Phone Number: 404-255-1930; Email: jmaakaron@bmtga.com

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
      • Contact: Caitlin Guzowski, MBA, MHA, CCRC; Phone Number: 404-851-8523; Email: caitlin.guzowski@northside.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Histologically confirmed large B-cell lymphoma
• Presence of one or more high-risk features
• Eligible to receive CAR-T according to the FDA label
• Measurable disease by CT or PET
• Adequate organ function unless related to lymphoma involvement:
• Pulse oximetry ≥ 92% on room air
• Ejection Fraction ≥ 40%
• ALT/AST < 5x ULN
• Bilirubin < 3 x ULN
• Calculated or measured creatinine Clearance ≥ 30 mL/min

Exclusion Criteria:

• KPS <60
• Second malignancy with a high metastatic potential within 3 years
• Active CNS involvement. Treated CNS disease is allowed
• Active HBV or HCV infection.
• Active uncontrolled infections
• Known HIV positive status
• Allogeneic transplant within 100 days of enrollment
• Active acute or chronic graft versus host disease
• History of acute or chronic pancreatitis
• History of myositis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Axatilimab + Commercial CAR T cell therapy	Drug: Axatilimab; Dose Level -1: 0.1mg/kg Dose Level +1: 0.3mg/kg Dose Level +2: 1mg/kg Dose Level +3: 3mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the recommended Phase 2 dose (RP2D) of axatilimab	Determine the recommended Phase 2 dose (RP2D) of axatilimab in combination with CAR T cell therapy by following a fast-track dose escalation design and assessing adverse events, using the CTCAE Version 6, related to axatilimab	1 year
Estimate 1 year progression-free survival	Estimate 1 year progression-free survival by assessing disease status at 1 year following CAR T infusion	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate overall response rate	Estimate overall response rate (a combination of complete and partial responders) by assessing disease status at 1 year following CAR T infusion	1 year
Estimate the overall survival of patients	Estimate the overall survival of patients by following survival status and cause of death for 1 year after CAR T infusion	1 year
Evaluate duration of response	Evaluate duration of response by assessing disease status at multiple timepoints (Days +30, 100, 180, and 365) within 1 year after CAR T infusion	1 year
Characterize the safety of axatilimab in combination with CAR T therapy	Characterize the safety of axatilimab in combination with CAR T therapy by assessing the incidence of cytokine release syndrome and immune-effector cell associated neurotoxcity syndrome according to ASTCT consensus criteria	1 year
Characterize the safety of axatilimab in combination with CAR T therapy	Characterize the safety of axatilimab in combination with CAR T therapy by assessing the incidence of grade 3 and 4 adverse events using the CTCAE version 6 criteria	1 year

Collaborators and Investigators

• Sponsor: Northside Hospital, Inc.

Publications and helpful links

General Publications

• Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
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• Carniti C, Caldarelli NM, Agnelli L, Torelli T, Ljevar S, Jonnalagadda S, Zanirato G, Fardella E, Stella F, Lorenzini D, Brich S, Arienti F, Dodero A, Chiappella A, Magni M, Corradini P. Monocytes in leukapheresis products affect the outcome of CD19-targeted CAR T-cell therapy in patients with lymphoma. Blood Adv. 2024 Apr 23;8(8):1968-1980. doi: 10.1182/bloodadvances.2024012563.
• Jain MD, Zhao H, Wang X, Atkins R, Menges M, Reid K, Spitler K, Faramand R, Bachmeier C, Dean EA, Cao B, Chavez JC, Shah B, Lazaryan A, Nishihori T, Hussaini M, Gonzalez RJ, Mullinax JE, Rodriguez PC, Conejo-Garcia JR, Anasetti C, Davila ML, Locke FL. Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma. Blood. 2021 May 13;137(19):2621-2633. doi: 10.1182/blood.2020007445.
• Wang J, Gao K, Lei W, Dong L, Xuan Q, Feng M, Wang J, Ye X, Jin T, Zhang Z, Zhang Q. Lymphocyte-to-monocyte ratio is associated with prognosis of diffuse large B-cell lymphoma: correlation with CD163 positive M2 type tumor-associated macrophages, not PD-1 positive tumor-infiltrating lymphocytes. Oncotarget. 2017 Jan 17;8(3):5414-5425. doi: 10.18632/oncotarget.14289.
• Marchesi F, Cirillo M, Bianchi A, Gately M, Olimpieri OM, Cerchiara E, Renzi D, Micera A, Balzamino BO, Bonini S, Onetti Muda A, Avvisati G. High density of CD68+/CD163+ tumour-associated macrophages (M2-TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B-cell lymphoma. Hematol Oncol. 2015 Jun;33(2):110-2. doi: 10.1002/hon.2142. Epub 2014 Apr 8. No abstract available.
• Li YL, Shi ZH, Wang X, Gu KS, Zhai ZM. Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count. BMC Cancer. 2019 Nov 6;19(1):1049. doi: 10.1186/s12885-019-6208-x.
• Cencini E, Fabbri A, Schiattone L, Sicuranza A, Mecacci B, Granai M, Mancini V, Lazzi S, Bocchia M, Leoncini L. Prognostic impact of tumor-associated macrophages, lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma. Am J Blood Res. 2020 Aug 25;10(4):97-108. eCollection 2020.
• Wang Z, Jiang R, Li Q, Wang H, Tao Q, Zhai Z. Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients. J Clin Med. 2021 Apr 19;10(8):1768. doi: 10.3390/jcm10081768.
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• Benner B, Scarberry L, Suarez-Kelly LP, Duggan MC, Campbell AR, Smith E, Lapurga G, Jiang K, Butchar JP, Tridandapani S, Howard JH, Baiocchi RA, Mace TA, Carson WE 3rd. Generation of monocyte-derived tumor-associated macrophages using tumor-conditioned media provides a novel method to study tumor-associated macrophages in vitro. J Immunother Cancer. 2019 May 28;7(1):140. doi: 10.1186/s40425-019-0622-0.
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• Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014 Jul 17;41(1):49-61. doi: 10.1016/j.immuni.2014.06.010.
• Iacoboni G, Navarro V, Martin-Lopez AA, Rejeski K, Kwon M, Jalowiec KA, Amat P, Reguera-Ortega JL, Gallur L, Blumenberg V, Gutierrez-Herrero S, Roddie C, Benzaquen A, Delgado-Serrano J, Sanchez-Salinas MA, Bailen R, Carpio C, Lopez-Corral L, Hernani R, Bastos M, O'Reilly M, Martin-Martin L, Subklewe M, Barba P. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2024 Jan 10;42(2):205-217. doi: 10.1200/JCO.23.01097. Epub 2023 Oct 24.
• Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, D'Aveni-Piney M, Oberic L, Bodet-Milin C, Bories P, Olivier P, Lafon I, Berriolo-Riedinger A, Galli E, Bernard S, Rubio MT, Bossard C, Meignin V, Merlet P, Feugier P, Le Gouill S, Ysebaert L, Casasnovas O, Meignan M, Chevret S, Thieblemont C. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020 Nov 24;4(22):5607-5615. doi: 10.1182/bloodadvances.2020003001.
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• Dean EA, Mhaskar RS, Lu H, Mousa MS, Krivenko GS, Lazaryan A, Bachmeier CA, Chavez JC, Nishihori T, Davila ML, Khimani F, Liu HD, Pinilla-Ibarz J, Shah BD, Jain MD, Balagurunathan Y, Locke FL. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Jul 28;4(14):3268-3276. doi: 10.1182/bloodadvances.2020001900.
• Beyar Katz O, Perry C, Grisariu-Greenzaid S, Yehudai-Ofir D, Luttwak E, Avni B, Zuckerman T, Sdayoor I, Stepensky P, Ringelstein-Harlev S, Bar-On Y, Libster D, Sharvit L, Amit O, Greenbaum U, Gold R, Herishanu Y, Benyamini N, Avivi I, Ram R. Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study. Eur J Haematol. 2023 Jul;111(1):63-71. doi: 10.1111/ejh.13968. Epub 2023 Apr 10.

Study record dates

Study Major Dates

• Study Start (Estimated): October 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: June 5, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Pyloric Stenosis; Gastric Outlet Obstruction; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Pyloric Stenosis, Hypertrophic; axatilimab
• Other Study ID Numbers: NSH 1445

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No