A Clinical Trial Targeting CEA Chimeric Antigen Receptor T (CAR-T) for CEA Positive Advanced Malignant Solid Tumors

NCT06043466 | Recruiting Phase 1

• 1 other identifier: PB06
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-arm, open, dose-increasing phase I clinical study to explore the safety, tolerability and pharmacokinetic characteristics of the drug C-13-60 cells, and preliminarily observe the efficacy of the drug in CEA positive late malignant solid tumors, and explore the applicable dose regimen for phase II clinical trials.

Conditions

Colorectal Cancer; Esophagus Cancer; Gastric Cancer; Pancreas Cancer; Non-small Cell Lung Cancer; Breast Cancer; Bile Duct Cancer

Keywords

CAR-T; CEA; CEA-positive advanced/metastatic solid tumors

Outcome Measures

Primary Outcomes (2)

• To determine the dose range and DLT of C-13-60 cells for CEA positive advanced malignant solid tumors [Safety and Tolerability]

  The incidence of adverse events (TEAE) after treatment; Incidence of treatment-related adverse events; Adverse evens of Special Interest (AESI);

  1 month

• To obtain the maximum tolerable dose of C-13-60 cells [Safety and Tolerability]

  Incidence and number of dose-limiting toxicity (DLT) cases，Dose-limiting toxicity after CAR-T cell infusion

  1month

Secondary Outcomes (5)

• Disease control rate (DCR) within 3 months after infusion of C-13-60 cell preparation[Effectiveness]

  3 months

• Area under the curve (AUCS) of C-13-60 cell [Cell dynamics]

  3 months

• Maximum concentration (CMAX) of C-13-60 cell [Cell dynamics]

  3 months

• Maximum time (TMAX) of C-13-60 cell[Cell dynamics]

  3 months

• The content of CEA in peripheral blood after infusion of C-13-60 cell [Cell dynamics]

  3 months

Other Outcomes (4)

• Objective response rate (ORR) of C-13-60 cell treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  2 years

• Duration of Response (DOR) of C-13-60 cell treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  2 years

• Progress-free survival(PFS) of C-13-60 cell treatment in patients with CEA-positive advanced malignancies[Effectiveness]

  2 years

Study Arms (1)

Intravenous of CEA-targeted CAR-T

EXPERIMENTAL

Infusion of CEA-targeted CAR-T cells by dose of 2-10x10\^6 cells/kg

Biological: CEA-targeted CAR-T cells

Interventions

CEA-targeted CAR-T cells BIOLOGICAL

Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.

Intravenous of CEA-targeted CAR-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, male or female;
• Patients with advanced malignant solid tumors confirmed by histology or pathology, including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer, non-small cell lung cancer, breast cancer, and cholangiocarcinoma;
• Progression or intolerance occurs after receiving systematic standard therapy according to guidelines,(systemic therapy including but not limited to systemic chemotherapy, molecular targeting, etc.) and is not suitable for surgery or local therapy (including ablative therapy, interventional therapy, and radiation therapy), among which colorectal cancer needs to receive at least third-line therapy failure or intolerance or inapplicability. Esophageal, gastric, non-small cell lung, breast, and cholangiocarcinoma require at least second-line treatment failure or intolerance or inadequacy, and pancreatic cancer require at least first-line treatment failure or intolerance or inadequacy:
• Advanced colorectal cancer: progression or intolerance or inadequacy after third-line standard therapy including cetuximab ± Irinotecan/regorafenib /fruquintinib/trifluridine；
• Advanced or metastatic esophageal cancer/esophagogastric junction cancer: patients with esophageal cancer who progress or are intolerant or inapplicable after second-line therapy including PD-1 MAB /PD-L1 mab; Patients with esophagogastric junction cancer progressed or were intolerant or inapplicable after second-line therapy including taxane or irinotecan or PD-1 /PD-L1 monoclonal antibody; For HER-2 positive patients, trastuzumab containing system therapy should fail or be intolerable or not applicable;
• Advanced/metastatic gastric cancer: the combination of PD-1 MAB /PD-L1 MAB and chemotherapy has been developed or is not tolerated or suitable; For HER-2 positive patients, systemic treatment containing trastuzumab should fail or be intolerable or inapplicable.
• Patients with advanced, metastatic, or recurrent non-small cell lung cancer who have received systemic treatment progression or intolerance, including: Patients with positive driver genes (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET) should receive targeted therapy failure or drug resistance (squamous cell carcinoma does not require driver gene testing). In addition, patients with EGFR-positive driver gene who are resistant to first-line EGFR-Tkis and who are positive for EGFR T790M mutations need to be treated with third-generation EGFR-TKI (such as Osimertinib, almonertinib, or furmonertinib) after failure or resistance. For patients with positive ALK fusion and drug resistance after first-line crizotinib treatment, second-line treatment with ceritinib or alectinib should fail or be resistant; Patients with PD-L1 expression (PD-L1 TPS≥1%) should undergo immune checkpoint inhibitor treatment failure or intolerance; In patients with negative driver genes, the disease progresses or becomes intolerable after chemotherapy with platinum-containing regiments-such as Camrelizumab, Pembrolizumab, Tislelizumab, Sintilimab or Atezolizumab combined with pemetrexed
• Advanced, metastatic breast cancer: HER-2 positive patients need to have received anti-HER-2 therapy, hormone receptor positive patients need to receive endocrine therapy and other standard treatments have failed or are intolerable or not applicable, and rescue chemotherapy for those who have failed/are intolerable or triple-negative breast cancer (including: Gemcitabine + cisplatin/carboplatin, albumin paclitaxel/other taxoid drugs + cisplatin/carboplatin) fail or are not tolerated or suitable;
• Locally advanced or metastatic pancreatic cancer: advanced or intolerant or inappropriate after at least first-line treatment, including: Gemcitabine + albumin-bound paclitaxel/cisplatin/erlotinib/capecitabine/tegafur/Nimotuzumab, or FOLFIRINOX (oxaliplatin + irinotecan +LV+5-FU), or mFOLFIRINOX (oxaliplatin + irinotecan + calcium folinate +5-FU);
• Subjects with positive CEA (IHC score 3+) in tumor tissue samples (paraffin sections or fresh tissue specimens or puncture biopsy samples) within 3 months before screening; If the immunohistochemical results of the tumor samples are more than 3 months from the time of screening, the patient needs to re-biopsy; If the tumor specimens are not available or the amount is too small for immunohistochemical detection of CEA, the CEA positive can be confirmed by re-staining of previous tissue specimens, and the peripheral blood serum CEA≥2.0×ULN can be included in the group.
• Have at least one evaluable target lesion according to RECIST 1.1 criteria;
• Colorectal cancer, esophageal cancer, non-small cell lung cancer, breast cancer, stomach cancer, cholangiocarcinoma ECOG 0 \~ 1 score, pancreatic cancer ECOG 0 \~ 2 score;
• Expected survival time is more than 12 weeks;
• No serious mental disorders;
• Unless otherwise stated, the subject's vital organ functions shall meet the following conditions:

You may not qualify if:

• People who have received CAR-T therapy or other gene-modified cell therapy;
• Patients with BMS with clinical symptoms or lesions located in key parts of the brain at the time of screening, patients with BMS without clinical symptoms or lesions located in non-critical parts of the brain should be evaluated by researchers or specialists to gain more than the risk.
• Received any of the following medications or treatments before screening:
• Received other investigational drugs or treatments that are not on the market within 4 weeks prior to screening;
• Received live attenuated vaccine within 4 weeks prior to screening;
• Received radioactive iodine-125 particle implantation within 8 weeks prior to screening;
• Received the following drugs or treatments before apheresis:
• received the equivalent of \&gt within 2 weeks prior to apheresis; 10mg/ day of prednisone for systemic steroids, except inhaled steroids;
• Received anti-PD-1 / PD-L1 monoclonal antibody treatment within 4 weeks before apheresis; Received chemotherapy, targeted therapy, or other investigational agents within 2 weeks of preapheresis or at least 5 drug half-lives (whichever is shorter);
• There is an active or uncontrolled infection that requires systemic treatment within 1 week prior to screening;
• Subjects with intestinal obstruction, active gastrointestinal bleeding, history of massive gastrointestinal bleeding within 3 months, severe gastroduodenal ulcer, severe ulcerative colitis and other severe intestinal inflammation;
• History of severe respiratory disease;
• There are a large number of serous effusions that cannot be controlled by treatment (such as pleural effusions, abdominal effusions and pericardial effusions);
• Have any of the following heart conditions:
• New York Heart Association (NYHA) Stage III or IV congestive heart failure;

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead
• Zhejiang University: collaborator

Study Sites (2)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Stomach Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Bile Duct Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases

Study Officials

• Ying Yuan, M.D

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

• Weijia Fang, M.D

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Yuan, M.D

CONTACT

13858193601; yuanying1999@tom.com

Weijia Fang, M.D

CONTACT

13758211655; weijiafang@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2023
• First Posted: September 21, 2023
• Study Start: August 11, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 21, 2023

Record last verified: 2023-09

Locations

CN (2)