Allogeneic Gammadelta T Cells Combined With Interferon-α1b or PD-1 Monoclonal Antibody in Stage III-IV Amenable to Surgical Resection Melanoma

NCT06212388 | Not Yet Recruiting Early Phase 1

• 1 other identifier: GDT-001-08
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of allogeneic γδ T cells combined with recombinant human interferon-α1b (IFN-α1b) or PD-1 monoclonal antibody in neoadjuvant treatment of patients with Stage III-IV resectable melanoma.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (4)

• Rate of Pathological Complete Response (pCR)

  Investigators will measure the rate of pCR after surgery.

  at 12 weeks

• Rate of Major Pathological Response (mPR)

  Investigators will measure the rate of mPR after surgery.

  at 12 weeks

• Rate of Partial Pathological Response (pPR)

  Investigators will measure the rate of pPR after surgery.

  at 12 weeks

• Overall Response Rate(ORR)

  ORR will be measured after neoadjuvant therapy (for participants who have measurable disease per RECIST 1.1 at start of neoadjuvant therapy).

  up to 12 weeks

Secondary Outcomes (4)

• Event Free survival(EFS)

  From randomization up to 3 years after surgery

• Relapse Free Survival (RFS)

  After surgery up to 3 years

• 3 Year Overall Survival (OS)

  After surgery up to 3 years

• Incidence of Adverse Events (AEs)

  After surgery up to 13 months

Study Arms (2)

group A: IFN-α1B+ γδ T cells

EXPERIMENTAL

Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles) Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments. Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks. Recombinant human interferon α1b administered 300μg every other day.

Biological: Ex-vivo expanded allogeneic γδ T cells; Drug: Recombinant human interferon α1b

group B: Palizizumab+ γδ T cells

ACTIVE COMPARATOR

Stage 1: Neoadjuvant stage (Week 1-9, 3 cycles) Stage 2: Surgical period (2 weeks, ±7 days after the last dose of neoadjuvant therapy) After multidisciplinary MDT team evaluation, the primary lesion and metastasis were resected in the corresponding departments. Stage 3: Postoperative adjuvant period (3 weeks ±7 days -45 weeks, 15 cycles) γδ T cells administered intravenously every three weeks.Pembrolizumab administered 200mg intravenously every three weeks.

Biological: Ex-vivo expanded allogeneic γδ T cells; Drug: Pembrolizumab

Interventions

Ex-vivo expanded allogeneic γδ T cells BIOLOGICAL

Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδT cells from donors will be adoptively transfused.

group A: IFN-α1B+ γδ T cells; group B: Palizizumab+ γδ T cells

Recombinant human interferon α1b DRUG

Recombinant human interferon α1b is a protein with potent antiviral, antiproliferative and immunomodulatory properties.

group A: IFN-α1B+ γδ T cells

Pembrolizumab DRUG

Pembrolizumab is a recombinant, humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.

group B: Palizizumab+ γδ T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Aged 18-75. 2. ECOG performance status of 0 or 1 3. Life expectancy ≥ 3 months; 4. Histologically or cytologically confirmed diagnosis of resectable stage III-IV melanoma by the American Joint Committee on Cancer (AJCC) (the 8th Edition). (Note: uveal melanoma cases are excluded) 5. Adequate organ and marrow function (within 4 weeks prior to study treatment initiation): 6. A negative urine or plasma β-HCG test result is required at screening for female patients of childbearing potential.
• \. Contraception is required for patients and their partners throughout the trial and within 1 year after the last dose of study treatment.
• \. Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
• \. Be willing to signed a written informed consent document before enrollment.

You may not qualify if:

• \. History of allergic reactions attributed to compounds of similar chemical or biologic composition to ex-vivo expanded allogeneic γδ T cells, recombinant human interferon-α1b and PD-1 monoclonal antibody.
• \. Patients accepted other anti-tumor clinical trials within 4 weeks prior to study entry.
• \. Patients accepted anti-tumor radiotherapy within 4 weeks prior to study entry.
• \. Disease improved by in response to anti-tumor therapies within 4 weeks including perioperative chemotherapy, molecularly targeted therapy, PD-1/PD-L1/CTLA-4 immune therapy, anti-angiogenesis therapy, interferon, herbal supplements, and other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.
• \. Plan to take other systemic or local anti-tumor therapy during the current study 6. Systemic treatment with either corticosteroid (\> 10 mg /kg prednisone equivalents) or other immunosuppressive medications prior to 2 weeks prior to study dose initiation 7. Known hematologic malignancy, primary brain tumor, sarcoma or any other primary solid tumor unless the disease-free period is over 5 years.
• \. Imaging confirmed of central nervous system (CNS) metastases with or without meningeal carcinomatosis 9. Known severe hypersensitivity reaction of another adoptive immune cell therapy.
• \. Known active autoimmune disease requiring systemic treatment (such as corticosteroids or immunosuppressive medications) or related replacement therapies (such as thyroid hormone for hypothyroidism, insulin for diabetes or physiological glucocorticoid replacement therapy for adrenal or pituitary insufficiency) in the past 2 years.
• \. Surgery history within past 4 weeks, except for melanoma removal or partial removal.
• \. Major organs dysfunction. 13. Acute infections and any condition has potential risk of gastrointestinal bleeding or perforation, such as active gastrointestinal ulcer, known intra luminal metastases,inflammatory bowel disease; known abdominal fistula, gastrointestinal perforation or intraperitoneal abscess 4 weeks prior to entry of the study entry.
• \. Other diseases that may affect compliance or interfere with results interpretation including active opportunistic infections or progressing or severe infections , uncontrolled diabetes or pulmonary diseases including interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm.
• \. Known HIV or AIDS-related illness, or active HBV, HCV and tuberculosis. 16. A history of getting a live vaccine within 4 weeks prior to the first dose; a history of hematopoietic stimulating factor therapy such as colony-stimulating factor (CSF) and erythropoietin (EPO) within 2 weeks prior to the first dose; a history of major surgeon except for diagnosis within 4 weeks prior to the first dose.
• \. Diagnosis of a psychiatric or substance abuse disorder. 18. Individuals who are pregnant or breast-feeding or plan to conceive during the study period 19. Any other illness, laboratory abnormality, or situations that in the opinion of the principal investigator would compromise the patients' ability to tolerate treatment or would limit compliance with study requirements.

Sponsors & Collaborators

• Xijing Hospital: lead
• Beijing GD Initiative Cell Therapy Technology Co., Ltd.: collaborator

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

GuanNan Zhu, M.D.;Ph.D

CONTACT

0086-84775406-8403; to_rain77@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2024
• First Posted: January 18, 2024
• Study Start: January 24, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2028
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share