Therapy Detail
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| Therapy Name | hALK.CAR T cells + Lorlatinib |
| Synonyms | |
| Therapy Description | |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Lorlatinib | Lorbrena | PF-06463922|Lorviqua | ALK Inhibitor 33 ROS1 Inhibitor 22 | Lorbrena (lorlatinib) is a small molecule inhibitor of Alk and Ros1 fusion proteins, which may result in suppression of Alk and Ros1-mediated signaling thereby inhibiting cell growth and causing tumor regression (PMID: 26144315). Lorbrena (lorlatinib) is FDA approved for use in patients with ALK-positive non-small cell lung cancer (FDA.gov). |
| hALK.CAR T cells | hALK.CAR T cells are T-lymphocytes engineered to express a chimeric antigen receptor (CAR) targeting ALK linked to the CD8 alpha hinge and transmembrane domain, CD28 costimulatory domain, and CD3zeta signaling domain, which potentially induces cytoxicity against tumor cells with high Alk expression (PMID: 38039964). |
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| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK F1174L | neuroblastoma | sensitive | hALK.CAR T cells + Lorlatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment resulted in increased death of neuroblastoma cells harboring ALK F1174L when co-cultured with hALK.CAR T cells compared to control CAR-T cells in culture and the combination inhibited tumor growth and increased survival in a cell line xenograft model (PMID: 38039964). | 38039964 |
| ALK R1275Q | neuroblastoma | sensitive | hALK.CAR T cells + Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment resulted in increased death of neuroblastoma cells harboring ALK R1275Q when co-cultured with hALK.CAR T cells compared to control CAR-T cells in culture (PMID: 38039964). | 38039964 |
| ALK F1245C | neuroblastoma | sensitive | hALK.CAR T cells + Lorlatinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment resulted in increased death of cells derived from a patient-derived xenograft model of neuroblastoma harboring ALK F1245C when co-cultured with hALK.CAR T cells compared to control CAR-T cells in culture and the combination inhibited tumor growth and increased survival in a patient-derived xenograft (PDX) model (PMID: 38039964). | 38039964 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
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