CRTE7A2-01 TCR-T Cells for HPV-16 Positive Advanced Cancers

A Phase I Study to Evaluate the Safety, Tolerance and Efficacy of CRTE7A2-01 TCR-T Cells in HLA-A*02:01+ Subjects With HPV16 Positive Advanced Cervical, Anal, or Head and Neck Cancers and Other Solid Tumors

A single center, open, single arm dose escalation and dose expansion phase I study to evaluate the safety, tolerability, and efficacy of CRTE7A2-01 TCR-T cells in HLA-A*02:01+ Subjects HPV16 positive advanced cervical, anal, or head and neck cancers. The study will determine RP2D of CRTE7A2-01 TCR-T cell injection.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Anal Cancer; Head and Neck Cancers; Other Solid Tumors
• Intervention / Treatment: Drug: CRTE7A2-01 TCR-T cell therapy

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Wang, Master; Phone Number: 010-86464526; Email: wangsa@corregene.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age >18 years and 65 years. 2. Patients with advanced solid tumors (such as cervical cancer, head and neck tumors, anal cancer, and other malignancies) who have failed standard treatment confirmed by histology and/or cytology, or who are intolerant to such treatment, and for whom there is no effective therapy available after standard treatment failure are considered as end-stage patients. Specifically for:

1. Cervical cancer: a) Patients who have previously failed at least second-line systemic therapy (including at least one platinum-based regimen or anti-angiogenic therapy) and have shown disease progression or intolerance confirmed by pathological or radiological examination during or after the most recent treatment course, and are not amenable to treatment with surgery or radiotherapy, with no standard treatment options currently available for recurrent or metastatic cervical cancer.
2. Nasopharyngeal cancer: a) Patients who have previously failed at least third-line systemic therapy or are intolerant, not amenable to treatment with surgery or radiotherapy, with no standard treatment options currently available for recurrent or metastatic nasopharyngeal cancer; b) EB virus negative.
3. Head and neck squamous cell carcinoma: a) Patients who have previously failed at least second-line systemic therapy or are intolerant, with no standard treatment options currently available for recurrent or metastatic head and neck squamous cell carcinoma (non-nasal).

3. Confirmation of HPV16 positive and HLA-A*02:01 allele. 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. Patient received any genetically modified T cell therapy.
2. Patient is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist.
3. Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis.

4. Patients have any organ system function impairment 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<0.5 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. Patinets has 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 has 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 has a known active brain metastases. 10. Patient has a known myelodysplastic syndrome (MDS) or lymphoma. 11. Patient has 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 has a known active Hepatitis B or Hepatitis C. 13. Patient has a history of Human Immunodeficiency Virus (HIV) . 14. Patient has a history of syphilis. 15. Pregnant or lactating women. 16. Patient has 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; This study is a single-arm Phase I study, encompassing both dose escalation and dose expansion phases. Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2	Drug: CRTE7A2-01 TCR-T cell therapy; Drug 1: Fludarabine + Cyclophosphamide Drug 2: Interleukin-2 Drug 3: CRTE7A2-01 TCR-T Cell; Other Names: CRTE7A2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	Dose-limiting toxicity	28 days
RP2D	Recommended Phase 2 Dose	2 years
cevents (SAEs).	Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).	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
Overall Survival(OS)	Assessed by RECIST 1.1	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral blood TCR-T cell copy number	Peripheral blood TCR-T cell copy number	2 years

Collaborators and Investigators

• Sponsor: Corregene Biotechnology Co., Ltd
• Investigators: Principal Investigator: Yang Xiang, Doctor, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 6, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; TCR; HPV; T cell; Adoptive cell therapy; T cell receptor; E7
• 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
• Other Study ID Numbers: CRTE7A2-2302C

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