Journal article
A phase 1, first-in-human (FIH) study of the anti-HER2 CAR macrophage CT-0508 in subjects with HER2 overexpressing solid tumors
Journal of clinical oncology, v 40(16_suppl), pp 2533-2533
01 Jun 2022
Abstract
2533 Background: Most solid tumors are resistant to immunotherapy. In pre-clinical studies, CAR-M infiltrate tumors, phagocytose tumor cells, activate the tumor micro environment (TME), recruit T cells, and present tumor antigens to T cells leading to robust anti-tumor immunity. CT-0508 is a first in class CAR-M, comprised of autologous monocyte derived macrophages expressing an anti-HER2 CAR. Here we present preliminary clinical results from the CT-0508 Phase 1 FIH study. Methods: This multi-center, open-label study is evaluating CT-0508’s safety, tolerability, and manufacturing feasibility in 18 participants (pts) with advanced solid tumors overexpressing HER2 who have progressed on prior therapies. Monocytes are isolated from mobilized apheresis products, differentiated into macrophages and engineered with an anti-HER2 CAR. Group 1 pts (n = 9) receive a fractionated dose (D1, D3, D5) and Group 2 pts (n = 9) receive the full dose on D1. CT-0508 is administered without preparative chemotherapy (bridging is permitted). Serial blood samples, 1 pre and 2 post-treatment biopsies are collected to investigate safety, pharmacokinetics and mechanism of action. Results: Seven pts (4F/3M), median age 64 (49-73), have been treated [breast (2), esophageal (2), cholangiocarcinoma, ovarian and parotid gland cancers]. A median of 3 (2-10) prior lines of therapy have been administered, most pts (85.7%) received prior anti HER2 therapy. CT-0508 was successfully manufactured with high viability, purity and CAR expression, and was well tolerated with no dose limiting toxicities or AEs leading to discontinuation or dose modification. Two related SAEs were reported in the same pt (Grade 1 CRS, hospitalized for monitoring and Grade 2 infusion reaction, resolved within 1h). Three other pts had Grade 1-2 CRS; resolved within 4d with no use of tocilizumab needed. There were no major organ toxicities and no on-target off-tumor toxicities. Post-infusion cytokines were transiently elevated in most pts and were self-limiting. Among the 4 pts who reached week 8, the best overall response was stable disease (n = 3) and 1 pt progressed, with a median follow up of 8w. CT-0508 rapidly egressed from peripheral blood. CT-0508 CAR mRNA was detected in all tumor biopsies of the first 2 pts. CT-0508 activated the TME, with increased myeloid cell activation, T cell infiltration, activation and proliferation. TCR sequencing demonstrated peripherally expanding T cells enriched for tumor infiltrating lymphocyte clones, suggesting expansion of tumor reactive T cells. Correlative data from additional pts will be presented. Conclusions: In 7 pts, CT-0508 was safe and feasible to manufacture. Early correlative data demonstrate trafficking, TME modulation, and potential induction of anti-tumor T cell immunity. The study is actively enrolling. Clinical trial information: NCT04660929.
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Details
- Title
- A phase 1, first-in-human (FIH) study of the anti-HER2 CAR macrophage CT-0508 in subjects with HER2 overexpressing solid tumors
- Creators
- Kim Anna Reiss - University of PennsylvaniaYuan Yuan - City Of Hope National Medical CenterNaoto T. Ueno - The University of Texas MD Anderson Cancer CenterMelissa Lynne Johnson - Sarah Cannon Research InstituteSaar Gill - University of PennsylvaniaElizabeth Claire Dees - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC;Joseph Chao - City of Hope Comprehensive Cancer Center, Duarte, CA;Mathew Angelos - University of PennsylvaniaOlga Shestova - University of Pennsylvanya, Philadelphia, PA;Jonathan Stuart Serody - University of North Carolina at Chapel HillSaul Priceman - City of HopeDebora Barton - Carisma TherapeuticsRamona F. Swaby - Carisma TherapeuticsAmy Ronczka - Carisma TherapeuticsThomas Condamine - Carisma TherapeuticsDaniel Cushing - Carisma TherapeuticsRehman Qureshi - Carisma TherapeuticsMadison Kemp - Carisma TherapeuticsMichael Klichinsky - Carisma TherapeuticsYara Abdou - University of North Carolina at Chapel Hill
- Publication Details
- Journal of clinical oncology, v 40(16_suppl), pp 2533-2533
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Other Identifier
- 991019350357004721