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

• ClinicalTrials.gov Identifier: NCT05122221
• Recruitment Status: Recruiting
• First Posted: November 16, 2021
• Last Update Posted: June 28, 2022
• Sponsor: Corregene Biotechnology Co., Ltd
• Information provided by (Responsible Party): Corregene Biotechnology Co., Ltd

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer; Anal Cancer; Head and Neck Cancers	Drug: Fludarabine + Cyclophosphamide; Drug: Interleukin-2; Biological: CRTE7A2-01 TCR-T Cell	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: July 17, 2022
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: December 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Objective Response Rate（ORR） [ Time Frame: 2 years ]
   Assessed by RECIST 1.1
2. Disease Control Rate（DCR） [ Time Frame: 2 years ]
   Assessed by RECIST 1.1
3. Duration of Response（DOR） [ Time Frame: 2 years ]
   Assessed by RECIST 1.1
4. Progression-Free Survival（PFS） [ Time Frame: 2 years ]
   Assessed by RECIST 1.1

Other Outcome Measures:

1. Peripheral blood TCR-T cell copy number [ Time Frame: 2 years ]
2. Negative conversion rate among HPV-16 positive patients detected by tissue biopsy [ Time Frame: 2 years ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Sa Wang, Master; 8610-86464526-840; wangsa@corregene.com

Locations

China, Henan

The First Affiliated Hospital of Zhengzhou University; Recruiting

Zhengzhou, Henan, China, 450052

Contact: Yi Zhang, Doctor 0371-66295320 yizhang@zzu.edu.cn

Principal Investigator: Yi Zhang, Doctor

Sponsors and Collaborators

Corregene Biotechnology Co., Ltd

More Information

• Responsible Party: Corregene Biotechnology Co., Ltd
• ClinicalTrials.gov Identifier: NCT05122221
• Other Study ID Numbers: CRTE7A2-2107C
• First Posted: November 16, 2021
• Last Update Posted: June 28, 2022
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Corregene Biotechnology Co., Ltd:

3+3 dose escalation

Additional relevant MeSH terms:

Head and Neck Neoplasms; Anus Neoplasms; Neoplasms by Site; Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Cyclophosphamide; Fludarabine; Interleukin-2; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents