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

Cervical Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05122221
• Other study ID #: CRTE7A2-2107C
• Status: Recruiting
• Phase: Phase 1
• Start date: July 17, 2022
• Est. completion date: December 2024

Study information

• Verified date: November 2021
• Source: Corregene Biotechnology Co., Ltd
• Contact: Sa Wang, Master
• Phone: 8610-86464526-840
• Email: wangsa[@]corregene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 2024
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ? or ?.

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.

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms
• Cervical Cancer
• Head and Neck Cancers
• Head and Neck Neoplasms

Intervention

Drug:
• Fludarabine + Cyclophosphamide
Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 500mg/m²/day×3 days
• 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.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Corregene Biotechnology Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peripheral blood TCR-T cell copy number		2 years
Other	Negative conversion rate among HPV-16 positive patients detected by tissue biopsy		2 years
Primary	MTD	Maximum Tolerated Dose	28 days
Primary	DLT	Dose-limiting toxicity	28 days
Primary	RP2D	Recommended Phase II Dose	28 days
Primary	Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).	grade 1-5 (CTCAE)	2 years
Secondary	Objective Response Rate(ORR)	Assessed by RECIST 1.1	2 years
Secondary	Disease Control Rate(DCR)	Assessed by RECIST 1.1	2 years
Secondary	Duration of Response(DOR)	Assessed by RECIST 1.1	2 years
Secondary	Progression-Free Survival(PFS)	Assessed by RECIST 1.1	2 years