This is a open-label, multicenter study to assess the safety, tolerability, and preliminary efficacy of IPM514 in patients with esophageal squamous cell carcinoma. This study consists of dose escalation phase (IPM514 monotherapy) ,dose expansion phase (IPM514 combined with anti-PD-1 antibody) and the neoadjuvant therapy cohort(IPM514 combined with anti-PD-1 antibody, cisplatin and paclitaxel).The dose escalation and dose expansion stages will include patients with unresectable advanced, recurrent or metastatic ESCC who have failed first-line treatment. After confirming the preliminary safety and effectiveness in the dose escalation and dose expansion stages, a neoadjuvant therapy cohort study will be developed, and resectable ESCC subjects will be included.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Drug:IPM514 Intramuscular Injection A total of 7 administrations, including 2 cycles of vaccination with each cycle at QW × 3 doses; there is a 2-weeks interval between the two cycles, then followed by a boost dose 3 weeks after the 2'nd cycle.
Drug:IPM514 Intramuscular Injection Drug:tislelizumab intravenous administration The usage and dosage of the tislelizumab will be based on the drug instructions. IPM514 administration is planned to be concomitant with PD-1 antibody and to be stopped after 9 doses of treatment, while the PD-1 antibody will be continuously administered for a maximum of 1 year.
Drug:IPM514 Intramuscular Injection Drug:tislelizumab intravenous administration Drug:cisplatin intravenous administration Drug:paclitaxel intravenous administration In this stage, subjects will receive the treatment of IPM514 combined with Tislelizumab, cisplatin and paclitaxel. All four drugs will be administered once every 3 weeks (± 1 day). IPM514 will be administered for the first time on D0, and Tislelizumab, cisplatin and paclitaxel will be administered for the first time on D3 (the administration order: Tislelizumab - paclitaxel - cisplatin). IPM514 will be administered a total of 3 times, and PD-1 antibody, cisplatin and paclitaxel will all be administered a total of 2 times (that is, IPM514 is administered on D0/D21/D42, and Tislelizumab, paclitaxel and cisplatin are administered on D3/D24).
Peking University Cancer Hospital
Beijing, China
RECRUITINGSafety and tolerability
Dose escalation \& Dose expansion:(1) Incidence and severity of adverse events (AEs), immune-related adverse events (irAEs), serious adverse events (SAEs) assessed by NCI-CTCAE v5.0. (2) The incidence and titer of anti-drug antibodies (ADA)
Time frame: up to 12 months
The MTD, if any, and RP2D
Dose escalation \& Dose expansion:IPM514 will be determined based on safety, tolerability, PK, preliminary efficacy, and other available data
Time frame: up to 12 months
PK parameter
Dose escalation \& Dose expansion:mRNA quantitation in blood by qPCR
Time frame: up to 12 months
the pCR rate
Neoadjuvant Treatment Cohort:The rate of pathological complete response
Time frame: up to 12 months
Objective response rate (ORR)
Dose escalation \& Dose expansion:Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment
Time frame: up to 12 months
disease control rate (DCR)
Dose escalation \& Dose expansion:disease control rate (DCR) per RECIST 1.1 criteria according to investigators assessment
Time frame: up to 12 months
progression-free survival (PFS)
Dose escalation \& Dose expansion:Progression free survival (PFS) rates
Time frame: up to 12 months
overall survival (OS)
Dose escalation \& Dose expansion:Overall survival (OS) rates
Time frame: up to 12 months
duration of response (DOR)
Dose escalation \& Dose expansion:Duration of response (DOR) per RECIST 1.1 criteria according to investigators assessment
Time frame: up to 12 months
the MPR rate
Neoadjuvant Treatment Cohort:The rate of major pathological response
Time frame: up to 12 months
the rate of R0 resection
Neoadjuvant Treatment Cohort:the rate of R0 resection
Time frame: up to 12 months
AE
Neoadjuvant Treatment Cohort:The incidence and severity of adverse events (AEs), immune-related adverse events (irAEs), and serious adverse events (SAEs) as evaluated according to NCI-CTCAE v5.0;
Time frame: up to 12 months
Surgical safety
Neoadjuvant Treatment Cohort:surgical complications within 30 days after surgery or during the postoperative hospital stay, length of hospital stay, reoperation rate, and 30-day postoperative mortality rate;
Time frame: up to 12 months
Biological responses
Neoadjuvant Treatment Cohort:(1) Lymphocyte subset analysis, including T/B/NK cell count and phenotyping of memory T cell; (2) TAA-specific T cell identification through tetramer and intracellular cytokine production via flow cytometry; (3) Immune responses of CTLs via IFN-γ ELISPOT; (4) Single-cell phenotypic analysis.
Time frame: up to 12 months
Predictive biomarkers
Neoadjuvant Treatment Cohort:including but not limited to tumor tissue antigen expression, minimal residual disease (MRD) and blood-based tumor mutational burden (bTMB)
Time frame: up to 12 months
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