NCT03932565

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2019

Typical duration for phase_1

Geographic Reach
1 country

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 13, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

April 27, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 30, 2019

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2021

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2021

Completed
Last Updated

November 18, 2020

Status Verified

November 1, 2020

Enrollment Period

2.4 years

First QC Date

April 27, 2019

Last Update Submit

November 16, 2020

Conditions

Nectin4-positive Advanced Malignant Solid Tumor

Outcome Measures

Primary Outcomes (1)

  • Adverse events that are related to treatment

    Safety and tolerability measured by occurrence of study related adverse effects defined by NCI-CTCAE v4.03

    2 years

Secondary Outcomes (2)

  • 2 year overall survival(OS)

    2 years

  • 3 year progression free survival (PFS)

    3 years

Study Arms (1)

The fourth-generation CAR-T therapy

EXPERIMENTAL

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 .

Biological: CAR-T therapy for nectin4-positive malignant solid tumor

Interventions

CAR-T therapy for nectin4-positive malignant solid tumorBIOLOGICAL

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.

The fourth-generation CAR-T therapy

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
  • Age is 18 to 75 years old, gender is not limited; the Eastern Cancer Cooperative Group (ECOG) scores 0 to 3
  • Pathological diagnosis of malignant solid tumors.
  • Advanced malignant solid tumors meet the CSCO malignant tumor diagnosis and treatment guidelines (2018 version). (Flow or pathology shows that tumor cells express Nectin4 antigen and tumor-associated fibroblasts express FAP antigen)
  • Head magnetic resonance or CT examination showed no central invasion of malignant tumors.
  • Collection of peripheral blood mononuclear cells must be more than 2 weeks from radiotherapy and chemotherapy.
  • Peripheral blood neutrophils number ≥ 1000 / μl, platelets ≥ 50,000 / μl.
  • Heart, liver and kidney function: creatinine \<2.5mg/dl; ALT (alanine aminotransferase) / AST (aspartate aminotransferase) \<3 times lower than the upper limit of normal; total bilirubin \<2.0mg/dl.
  • Cardiac ejection fraction (EF) ≥ 50%, echocardiography without pericardial effusion.
  • Have fertility must be willing to use contraceptive methods.
  • The expected survival period is more than 12 weeks.
  • No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.

You may not qualify if:

  • Pregnant or lactating women.
  • Patients with uncontrollable active infections.
  • Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
  • Previously involved CAR-T cell therapies produced any uncontrolled disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

The Sixth Affiliated Hospital of Wenzhou Medical University

Lishui, Zhejiang, 323000, China

RECRUITING

Zhejiang QiXin Biotech

Wenzhou, Zhejiang, 325035, China

RECRUITING

Related Publications (11)

  • Wang LC, Lo A, Scholler J, Sun J, Majumdar RS, Kapoor V, Antzis M, Cotner CE, Johnson LA, Durham AC, Solomides CC, June CH, Pure E, Albelda SM. Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity. Cancer Immunol Res. 2014 Feb;2(2):154-66. doi: 10.1158/2326-6066.CIR-13-0027. Epub 2013 Nov 12.

    PMID: 24778279BACKGROUND

  • Lo A, Wang LS, Scholler J, Monslow J, Avery D, Newick K, O'Brien S, Evans RA, Bajor DJ, Clendenin C, Durham AC, Buza EL, Vonderheide RH, June CH, Albelda SM, Pure E. Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells. Cancer Res. 2015 Jul 15;75(14):2800-2810. doi: 10.1158/0008-5472.CAN-14-3041. Epub 2015 May 15.

    PMID: 25979873BACKGROUND

  • Joyce JA, Fearon DT. T cell exclusion, immune privilege, and the tumor microenvironment. Science. 2015 Apr 3;348(6230):74-80. doi: 10.1126/science.aaa6204.

    PMID: 25838376BACKGROUND

  • Challita-Eid PM, Satpayev D, Yang P, An Z, Morrison K, Shostak Y, Raitano A, Nadell R, Liu W, Lortie DR, Capo L, Verlinsky A, Leavitt M, Malik F, Avina H, Guevara CI, Dinh N, Karki S, Anand BS, Pereira DS, Joseph IB, Donate F, Morrison K, Stover DR. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res. 2016 May 15;76(10):3003-13. doi: 10.1158/0008-5472.CAN-15-1313. Epub 2016 Mar 24.

    PMID: 27013195BACKGROUND

  • Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010 Nov 5;330(6005):827-30. doi: 10.1126/science.1195300.

    PMID: 21051638BACKGROUND

  • Lopez M, Ghidouche A, Rochas C, Godelaine D, Carrasco J, Colau D, Hames G, Montero-Julian FA, Coulie PG, Olive D. Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4. Cancer Immunol Immunother. 2016 Oct;65(10):1177-88. doi: 10.1007/s00262-016-1877-7. Epub 2016 Aug 11.

    PMID: 27514672BACKGROUND

  • Targeting Nectin-4 in Bladder Cancer. Cancer Discov. 2017 Aug;7(8):OF3. doi: 10.1158/2159-8290.CD-NB2017-095. Epub 2017 Jun 20.

    PMID: 28634245BACKGROUND

  • Tsiatas M, Grivas P. Immunobiology and immunotherapy in genitourinary malignancies. Ann Transl Med. 2016 Jul;4(14):270. doi: 10.21037/atm.2016.06.29.

    PMID: 27563657BACKGROUND

  • Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: Challenges to Bench-to-Bedside Efficacy. J Immunol. 2018 Jan 15;200(2):459-468. doi: 10.4049/jimmunol.1701155.

    PMID: 29311388BACKGROUND

  • Mirzaei HR, Rodriguez A, Shepphird J, Brown CE, Badie B. Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications. Front Immunol. 2017 Dec 22;8:1850. doi: 10.3389/fimmu.2017.01850. eCollection 2017.

    PMID: 29312333BACKGROUND

  • Adachi K, Kano Y, Nagai T, Okuyama N, Sakoda Y, Tamada K. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346-351. doi: 10.1038/nbt.4086. Epub 2018 Mar 5.

    PMID: 29505028BACKGROUND

MeSH Terms

Interventions

Immunotherapy, Adoptive

Intervention Hierarchy (Ancestors)

Adoptive TransferImmunization, PassiveImmunizationImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • Bingmu Fang, M.D

    Lishui Country People's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Bingmu Fang, M.D

CONTACT

0578-2780108fbm636@163.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 27, 2019

First Posted

April 30, 2019

Study Start

February 13, 2019

Primary Completion

June 30, 2021

Study Completion

December 31, 2021

Last Updated

November 18, 2020

Record last verified: 2020-11

Locations

CN(2)