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DRUG:

CTX130

i
Other names: CTX130 , Anti-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells, CTX-130, CTX 130
Associations
Trials
Company:
CRISPR Therap
Drug class:
CD70-targeted CAR-T immunotherapy
Associations
Trials
20d
Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. (PubMed, Lancet Oncol)
In patients with heavily pretreated T-cell lymphoma, CTX130 showed manageable safety and a promising objective response rate. This study shows that allogeneic, readily available CAR T cells can be safely given to patients with relapsed or refractory T-cell lymphoma. A next-generation CAR T-cell therapy containing additional potency gene edits (CTX131) is in clinical development.
P1 data • Journal • CAR T-Cell Therapy
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CD70 (CD70 Molecule)
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cyclophosphamide • fludarabine IV • CTX130 • CTX131
9ms
CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma. (PubMed, Cancer Discov)
Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.
Journal • CAR T-Cell Therapy • Metastases
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CD70 (CD70 Molecule)
|
CTX130 • CTX131
9ms
A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies (COBALT-LYM) (clinicaltrials.gov)
P1, N=45, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting
Enrollment closed
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CTX130
over1year
A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory Renal Cell Carcinoma (COBALT-RCC) (clinicaltrials.gov)
P1, N=107, Active, not recruiting, CRISPR Therapeutics AG | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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CTX130
2years
Going after CD70 with CAR T, NK Cells. (PubMed, Cancer Discov)
CD70 has emerged as a promising solid tumor target for chimeric antigen receptor (CAR)-bearing T or natural killer (NK) cells, with one allogeneic CAR T-cell therapy, CTX130, showing preliminary efficacy in renal cell carcinoma. Further, assessments of a cord blood-derived CAR-NK alternative have started; the trial will be the first to use cryopreserved NK cells.
Journal
|
CD70 (CD70 Molecule)
|
CTX130
over2years
THE COBALT-LYM STUDY OF CTX130: A PHASE 1 DOSE ESCALATION STUDY OF CD70-TARGETED ALLOGENEIC CRISPR-CAS9–ENGINEERED CAR T CELLS IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) T-CELL MALIGNANCIES (EHA 2022)
Pts received lymphodepleting chemotherapy (LDC) with fludarabine 30mg/m 2 and cyclophosphamide 500mg/m 2 for 3 days, followed by CTX130. Conclusion We have observed clinically meaningful responses, including CRs with CTX130, the first CAR T directed against the novel target, CD70. CTX130 has an acceptable safety profile in pts with heavily pretreated R/R TCL and will be investigated further in an expansion phase of the study.
Clinical • P1 data • CAR T-Cell Therapy • IO biomarker
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B2M (Beta-2-microglobulin) • CD70 (CD70 Molecule)
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CD70 expression
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cyclophosphamide • fludarabine IV • CTX130
almost4years
[VIRTUAL] CD70 knockout: A novel approach to augment CAR-T cell function (AACR 2021)
In summary, KO of CD70 confers benefit to CAR-T cells that far exceeds KO of other checkpoint related genes, and this benefit was present regardless of the antigen being targeted. CD70 KO is included in the CTX130 investigational allogeneic CAR-T therapy currently in clinical trials.
CAR T-Cell Therapy • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • LAG3 (Lymphocyte Activating 3) • B2M (Beta-2-microglobulin) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
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CD70 expression
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CTX130
over4years
[VIRTUAL] Targeting T cell lymphomas with CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells (AACR-II 2020)
CD70 (CD27 ligand) is a candidate target antigen for T cell lymphomas and has been is the subject of clinical trials using an enhanced ADCC antibody (ARGX-110). Consistent with these prior observations, CTX130 exhibited high potency in vitro and in vivo against T cell lymphoma cells across a range of CD70 antigen density and representing different types of T cell lymphomas such as Sezary syndrome and cutaneous T cell lymphoma (CTCL). CTX130 may thus be a valid therapeutic to evaluate in T cell lymphoma patients.
CAR T-Cell Therapy • IO biomarker
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CD70 (CD70 Molecule) • CD27 (CD27 Molecule)
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cusatuzumab (ARGX-110) • CTX130