CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers

A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of CRTE7A2-01 TCR-T Cell for HPV16 Positive Advanced Cervical, Anal, or Head and Neck Cancers

A single center, open, single arm dose escalation phase I study to evaluate the safety, tolerability, and efficacy of CRTE7A2-01 TCR-T cell for HPV16 positive advanced cervical, anal, or head and neck cancers. The study will determine MTD of CRTE7A2-01 TCR-T cell injection, as well as investigate RP2D.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Anal Cancer; Head and Neck Cancers
• Intervention / Treatment: Drug: Fludarabine + Cyclophosphamide; Drug: Interleukin-2; Biological: CRTE7A2-01 TCR-T Cell

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Wang, Master; Phone Number: 8610-86464526-840; Email: wangsa@corregene.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Principal Investigator: Yi Zhang, Doctor
      • Contact: Yi Zhang, Doctor; Phone Number: 0371-66295320; Email: yizhang@zzu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥18 years and ≤65 years.
2. Histologically-confirmed cervical cancer, anal cancer, head and neck cancers with confirmed HPV16 infection and HLA-A*02:01 allele
3. Failure on or intolerance to systemic therapy for unresectable advanced cancer.
4. ECOG performance status of 0-1.
5. Estimated life expectancy ≥ 3 months.
6. Patients must have at least one measurable lesion defined by RECIST 1.1.
7. Female patients of childbearing age must undergo a serum pregnancy test within 7 days prior to study treatment and the results must be negative, and are willing to use a very effective and reliable method of contraception from screening through 6 months after the last dose of study treatment.
8. The patient must be willing to sign the informed consent form and have a good anticipation of compliance with study procedure.

Exclusion Criteria：

1. The proportion of T cell immune-related gene deletion mutations>5%.
2. Patient received any genetically modified T cell therapy.
3. Patient who is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist.
4. Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis.

5. Patients with any organ dysfuntion as defined below:

   • leukocytes<3.0 x 109/L
   • absolute neutrophil count >1.5 x 109/L
   • hemoglobin<90g/L
   • platelets <100 x 1010/L
   • lymphocytes<0.8 x 109/L
   • percentage of lymphocytes<15%
   • creatinine>1.5×ULN or creatinine clearance <50mL/min
   • total bilirubin>3×ULN; ALT/AST>3×ULN (patients with liver metastasis,>5×ULN)
   • INR>1.5×ULN; APTT>1.5×ULN
   • SpO2≤90%
6. Patients with serious medical conditions, disorders, and / or comorbidities, including, but are not limited to: severe heart disease, cerebrovascular disease, epileptic seizures, uncontrolled diabetes (CTCAE 5.0: FBG ≥ 2 grade), active infection, active digestive tract Ulcer, gastrointestinal bleeding, intestinal obstruction, pulmonary fibrosis, renal failure, respiratory failure.
7. Patient with a severe cardiovascular disease with 6 months before screening, including, but are not limited to, myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass grafting, Heart failure NYHA grade Ⅲ or Ⅳ.
8. Left Ventricular Ejection Fractions (LVEF) <50%.
9. Patient with a known active brain metastases.
10. Patient with a known myelodysplastic syndrome (MDS) or lymphoma.
11. Patient with a known active autoimmune disease, including , but are not limited to, acquired or congenital immunodeficiency disease, allogeneic organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease.
12. Patient with a known active Hepatitis B or Hepatitis C.
13. Patient with a history of Human Immunodeficiency Virus (HIV) .
14. Patient with a history of syphilis.
15. Pregnant or lactating women.
16. Patient with a known active mental and neurological diseases.
17. The principal investigator judged that it is not suitable to participate in this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CRTE7A2-01 TCR-T cell therapy; Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2

Drug: Fludarabine + Cyclophosphamide; Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days; Drug: Interleukin-2; Interleukin-2 20,000,000 IU/time infused within 15 minutes approximately every 8 hours (according to the subject's tolerance, the interval between medications can be extended to 24 hours) for a maximum usage time up to 14 days.; Biological: CRTE7A2-01 TCR-T Cell; On day 0, the TCR-T cells will be administered one time, each bag of cell intravenously within 20 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum Tolerated Dose	28 days
DLT	Dose-limiting toxicity	28 days
RP2D	Recommended Phase II Dose	28 days
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).	grade 1-5 (CTCAE)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	Assessed by RECIST 1.1	2 years
Disease Control Rate（DCR）	Assessed by RECIST 1.1	2 years
Duration of Response（DOR）	Assessed by RECIST 1.1	2 years
Progression-Free Survival（PFS）	Assessed by RECIST 1.1	2 years

Other Outcome Measures

Outcome Measure	Time Frame
Peripheral blood TCR-T cell copy number	2 years
Negative conversion rate among HPV-16 positive patients detected by tissue biopsy	2 years

Collaborators and Investigators

• Sponsor: Corregene Biotechnology Co., Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): July 17, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 5, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 22, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: 3+3 dose escalation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Head and Neck Neoplasms; Anus Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Interleukin-2
• Other Study ID Numbers: CRTE7A2-2107C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No