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.
This is a double-arm, single-center, randomized, open label Phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus recombinant human interferon α1b or PD-1 monoclonal antibody in patients with Stage III-IV resectable melanoma(AJCC 8th). We randomly assigned patients with stage III-IV melanoma that was amenable to surgical resection to three doses of neoadjuvant γδT cells plus IFN-α1b or γδT cells plus pembrolizumab , surgery, and 15 doses of adjuvant γδT cells plus IFN-α1b or γδT cells plus pembrolizumab. The primary endpoints are pathological response rate after 3 cycles of treatment, including: complete pathological response rate (pCR), major pathological response rate (MPR), partial pathological response rate (pPR); preoperative imaging response rate (RECIST v1.1) was evaluated, including complete response (CR), partial response (PR), stable disease (SD), and disease progression (PD); and proportion of patients who do not need surgery due to remission. The second endpoints are event-free survival (EFS), relapse free survival (RFS), and overall survival (OS, 3 years after surgery). The safety profile of the combined γδT cells/IFN-α1b regimen and γδT cells/ pembrolizumab regimen will be monitored, we will evaluate the numbers and severity of toxicity per the Criteria for Adverse Events version 5 (CTCAEv) including but not limited to all adverse events (AE), incidence of surgery-related adverse events, and proportion of inoperable patients (due to disease progression or treatment-related adverse events).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
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.
Recombinant human interferon α1b is a protein with potent antiviral, antiproliferative and immunomodulatory properties.
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.
Rate of Pathological Complete Response (pCR)
Investigators will measure the rate of pCR after surgery.
Time frame: at 12 weeks
Rate of Major Pathological Response (mPR)
Investigators will measure the rate of mPR after surgery.
Time frame: at 12 weeks
Rate of Partial Pathological Response (pPR)
Investigators will measure the rate of pPR after surgery.
Time frame: 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).
Time frame: up to 12 weeks
Event Free survival(EFS)
EFS is defined as time from randomization to melanoma progression (irresectable stage III or stage IV disease), melanoma recurrence, treatment-related death, or melanoma-related death, whichever occurs first. Occurrence of a new primary melanoma during treatment/follow-up is also regarded as an event. Presurgical resectable progression to stage III disease is not defined as an event, even as death to another reason than melanoma or the study treatment.
Time frame: From randomization up to 3 years after surgery
Relapse Free Survival (RFS)
RFS is defined as time from surgery until disease relapse.
Time frame: After surgery up to 3 years
3 Year Overall Survival (OS)
The 3 years after surgery OS rate of patients with γδ T cells plus IFN-α1B or γδ T cells plus pembrolizumab,From date of enrollment until the date of death from any cause.
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Time frame: After surgery up to 3 years
Incidence of Adverse Events (AEs)
Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Time frame: After surgery up to 13 months