Phase Ib Trial of CAR-T Hepatic Artery Infusions Followed by Selective Internal Radiation Therapy (SIRT) With Yttrium-90 Sir-Spheres® for CEA-Expressing Liver Metastases

This is an open label fixed dose phase Ib of anti-CEA CAR-T cells hepatic artery infusions and yttrium-90 SIR-Spheres in patients with CEA-expressing liver metastases.

Start Date01 Apr 2015

Sponsor / Collaborator

Roger Williams Realty Corp.

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100 Clinical Results associated with Anti-CEA CAR-T cells(Roger Williams Medical Center)

100 Translational Medicine associated with Anti-CEA CAR-T cells(Roger Williams Medical Center)

100 Patents (Medical) associated with Anti-CEA CAR-T cells(Roger Williams Medical Center)

Literatures (Medical) associated with Anti-CEA CAR-T cells(Roger Williams Medical Center)

01 Jan 2021·OncoImmunologyQ2 · MEDICINE

Tumor regression and immunity in combination therapy with anti-CEA chimeric antigen receptor T cells and anti-CEA-IL2 immunocytokine

Q2 · MEDICINE

ArticleOA

Author: Cha, Seung E. ; Kujawski, Maciej ; J. Yazaki, Paul ; Shively, John E. ; Brown, Christine

Targeted immunotherapy of solid cancers with chimeric antigen receptor (CAR) T cells and immunocytokines are attractive options in that they both rely on the specificity of tumor-targeted antibodies. Since carcinoembryonic antigen (CEA) expression in both colon and breast cancers is correlated with poor prognosis, it was chosen as a model tumor target in immunocompetent CEA transgenic (CEATg) mice. A second-generation anti-CEA CAR derived from CEA-specific antibody T84.66 was used to treat murine MC38 colon or E0771 breast carcinomas transfected with CEA. Anti-CEA CAR vs. mock transduced T cells exhibited a CEA-specific cytotoxic and IFN __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__γ dose response to both CEA transfected cell lines vs. their CEA-negative controls. Anti-CEA CAR vs. mock transduced T cells delayed the median survival of CEA transfected s.c. MC38 or orthotopic E0771 tumor-bearing CEATg mice by 2 days. With the addition of one-day prior cyclophosphamide (CY) lymphodepletion, anti-CEA CAR T cell treatment delayed the median survival of MC38/CEA and E0771/CEA tumor-bearing CEATg mice by ten and 3 days, respectively. Since CAR T cells require IL2 for survival and expansion, anti-CEA-IL2 immunocytokine (ICK) treatment was performed post CAR T cell therapy. Single ICK treatment 1 day after CY plus anti-CEA CAR T cell therapy in the MC38/CEA model, and two ICK treatments every 3 days after CY plus anti-CEA CAR T cell therapy in the E0771/CEA model were ineffective, while four ICK treatments every 3 days after CY plus anti-CEA CAR T cell therapy completely eradicated MC38/CEA tumor growth and induced tumor immunity when the mice were re-challenged with tumor. These studies show the therapeutic potential of anti-CEA CAR T cells combined with ICK to treat CEA-positive tumors. Abbreviations: CAR: Chimeric antigen receptor, CEA: Carcinoembryonic antigen, CEACAM5, ICK: Immunocytokine, CY: Cyclophosphamide, CEATg mouse: transgenic CEA mouse, TDLN: Tumor-draining lymph node.

01 Aug 2020·Journal for ImmunoTherapy of CancerQ2 · MEDICINE

HITM-SURE: Hepatic immunotherapy for metastases phase Ib anti-CEA CAR-T study utilizing pressure enabled drug delivery

Q2 · MEDICINE

ArticleOA

Author: Prince, Ethan ; Moody, Ashley E ; Armenio, Vincent ; Hardaway, John C ; Saied, Abdul ; Junghans, Richard P ; LaPorte, Jason ; Jordan, Kimberly R ; Knight, Robert ; Stancu, Mirela ; Guha, Prajna ; Schulick, Richard D ; Katz, Steven C ; Slansky, Jill E

In recent years, cell therapy technologies have resulted in impressive results in hematologic malignancies. Treatment of solid tumors with chimeric antigen receptor T-cells (CAR-T) has been less successful. Solid tumors present challenges not encountered with hematologic cancers, including high intra-tumoral pressure and ineffective CAR-T trafficking to the site of disease. Novel delivery methods may enable CAR-T therapies for solid tumor malignancies. A patient with liver metastases secondary to pancreatic adenocarcinoma received CAR-T targeting carcinoembryonic antigen (CEA). Previously we reported that Pressure-Enabled Drug Delivery (PEDD) enhanced CAR-T delivery to liver metastases 5.2-fold. Three doses of anti-CEA CAR-T were regionally delivered via hepatic artery infusion (HAI) using PEDD technology to optimize the therapeutic index. Interleukin-2 was systemically delivered by continuous intravenous infusion to support CAR-T in vivo. HAI of anti-CEA CAR-T was not associated with any serious adverse events (SAEs) above grade 3 and there were no on-target/off-tumor SAEs. Following CAR-T treatment, positron emission tomography-CT demonstrated a complete metabolic response within the liver, which was durable and sustained for 13 months. The response was accompanied by normalization of serum tumor markers and an abundance of CAR+ cells found within post-treatment tumor specimens. The findings from this report exhibit biologic activity and safety of regionally infused CAR-T for an indication with limited immune-oncology success to date. Further studies will determine how HAI of CAR-T may be included in multidisciplinary treatment plans for patients with liver metastases. ClinicalTrials.gov number, NCT02850536.

01 May 2020·Cancer Gene TherapyQ2 · MEDICINE

HITM-SIR: phase Ib trial of intraarterial chimeric antigen receptor T-cell therapy and selective internal radiation therapy for CEA+ liver metastases

Q2 · MEDICINE

Article

Author: Prince, Ethan ; Wang, Li Juan ; Katz, Steven C ; Guha, Prajna ; Junghans, Richard P ; Moody, Ashley ; Espat, N Joseph ; Hardaway, John ; Armenio, Vincent ; Cunetta, Marissa

Effective chimeric antigen receptor-modified T-cell (CAR-T) therapy for liver metastases (LM) will require innovative solutions to ensure efficient delivery and minimization of systemic toxicity. We previously demonstrated the safety of CAR-T hepatic artery infusions (HAI). We subsequently conducted the phase 1b HITM-SIR trial, in which six patients (pts) with CEA⁺ LM received anti-CEA CAR-T HAIs and selective internal radiation therapy (SIRT). The primary endpoint was safety with secondary assessments of biologic activity. Enrolled pts had a mean LM size of 6.4 cm, 4 pts had >10 LM, and pts received an average of two lines of prior systemic therapy. No grade 4 or 5 toxicities were observed, and there were no instances of severe cytokine-release syndrome (CRS) or neurotoxicity. The mean transduction efficiency was 60.4%. Following CAR-T HAI, reduced levels of GM-CSF-R, IDO, and PD-L1 were detected in LM, and serum CEA levels were stable or decreased in all subjects. Median survival time was 8 months (mean 11, range 4-31). Anti-CEA CAR-T HAI with subsequent SIRT was well tolerated, and biologic responses were demonstrated following failure of conventional therapy. HAI of CAR-T was once again confirmed not to be associated with severe CRS or neurotoxicity.

100 Deals associated with Anti-CEA CAR-T cells(Roger Williams Medical Center)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Liver metastases	Phase 1	United States	Sirtex Medical Pty Ltd.	01 Apr 2015
Liver metastases	Phase 1	United States	Roger Williams Realty Corp.	01 Apr 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02416466 (HITM-SIR, Pubmed \| Cancer Gene Ther) Manual	Phase 1	Liver metastases CEA Positive	4	Anti-CEA CAR-T+SIR-Spheres	rccwpqcupv(hebtxqagpy) = qymavkojny subcbatabb (jisvrlihiy ) View more	Positive	01 May 2020