NCT03932565

Interventional Therapy Sequential With the Fourth-generation CAR-T Targeting Nectin4/FAP for Malignant Solid Tumors

Clinical Trial Study of Interventional Therapy Sequential With the Fourth-generation CAR-T Cells (IL7 and CCL19 or / and IL12) Targeting Nectin4/FAP in the Treatment of Advanced Malignant Solid Tumors With Nectin4-positive

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: The Sixth Affiliated Hospital of Wenzhou Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

According to the high expression of tumor cell-associated antigen Nectin4 in patients with solid tumors such as non-small cell lung cancer, breast cancer, ovarian cancer, bladder cancer, and pancreatic cancer, and in order to target FAP-positive CAFs in the tumor-associated stroma, the Intravenous minimally invasive surgery combined with intratumoral injection of Nectin4/FAP-targeted fourth-generation CAR-T cells (expressing IL7 and CCL19, or IL12) are used to treat Nectin4-positive advanced malignant solid tumors, maximally eliminating residual cancer cells and preventing recurrence.

Detailed description

Currently, malignant tumors are the leading cause of death. Surgery, chemotherapy, radiation therapy, and targeted therapy have become the four foundations of cancer treatment for many years. With the development of science and technology, immunotherapy has become the "fifth pillar" of cancer treatment. The most hot topic in immunotherapy is CAR-T therapy. The basic principle of CAR-T therapy (chimeric antigen receptor-T cells) is mainly to use the patient's own immune cells to clear cancer cells. CAR is a core component of CAR-T, conferring T cell a HLA-independent way to recognize tumor antigens, allowing CAR-modified T cells to recognize a broader target than the natural T cell surface receptor TCR. The basic design of CAR includes a tumor associated antigen (TAA) binding region, an extracellular hinge region, a transmembrane region and an intracellular signaling region. The selection of target antigens is a key determinant of the specificity and effectiveness of CAR and the safety of genetically modified T cells themselves. Nectin-4 is a type I transmembrane protein whose extracellular domain is composed of three Ig-like domains (V-C-C type), which together with cadherin participate in the formation and maintenance of adhesion junctions. Nectin-4 is ubiquitously expressed in human embryonic cells but is hardly expressed in normal adult tissues. Nectin-4 is highly expressed on the surface of breast cancer, bladder cancer, non-small cell lung cancer, and pancreatic cancer cells, and plays a key role in the occurrence, invasion and metastasis of these epithelial malignancies. In conclusion, Nectin-4 is one of the important targets for the diagnosis and treatment of many solid tumors. The antibody-conjugated drug Enfortumab Vedotin targeting Nectin-4 was highly effective in Phase I clinical trials in 81 advanced bladder cancers, and was awarded FDA breakthrough therapy in March 2018. Fibroblast activation protein (FAP) belongs to the serine protease family and is highly expressed on the surface of cancer-associat

Conditions

• Nectin4-positive Advanced Malignant Solid Tumor

Interventions

Type	Name	Description
BIOLOGICAL	CAR-T therapy for nectin4-positive malignant solid tumor	The Intravenous minimally invasive surgery combined with intratumoral injection of Nectin4/FAP-targeted the fourth-generation CAR-T cells (expressing IL7 and CCL19, or IL12) are used to treat Nectin4-positive advanced malignant solid tumors, maximally eliminating residual cancer cells and preventing recurrence.

Timeline

• Start date: 2019-02-13
• Primary completion: 2021-06-30
• Completion: 2021-12-31
• First posted: 2019-04-30
• Last updated: 2020-11-18

Locations

2 sites across 1 country: China