Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
This is a Phase 1, open-label, multicenter study to assess the safety, tolerability, and preliminary efficacy of IPM514 in patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma. IPM514 will be administered by intramuscular injection. Six ascending dose cohorts of IPM514 will be evaluated, with each cohort planned to enroll 3-6 qualified participants after a screening period of up to 28 days, following 3 + 3 study design format, the dose levels are as follows: 50 µg, 100 µg, 200 µg, 300 µg, 450 µg, and 600 µg. It may be adjusted during the dose escalation study based on the emerging data of safety, efficacy, and biological responses upon Safety Monitoring Committee (SMC) approval.
Interventions
BIOLOGICALIPM514
2 primary immunization cycles: IPM514 will be administered once a week (QW) for 3 consecutive doses per cycle, there will be a 2-week interval between the two cycles. Maintenance treatment: 6 doses administered every 3 weeks (Q3W), and 4 doses administered every 6 weeks (Q6W), if treatment continuously benefit the participant.
Sponsors
Beijing Immupeutics Medicine Technology Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* To be eligible to participate in this study, a patient must meet all the following criteria: 1. Male or female, aged ≥ 18 years on the day the patient voluntarily agrees to participate in the study. 2. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments. 3. Histologically confirmed diagnosis of ESCC. 4. Patients' prior systemic therapy must have included at least a PD-1/PD-L1 inhibitor and a platinum-based chemotherapy regimen and have disease progression confirmed by imaging during or after these treatments. NOTE: • Patients with disease progression that occurs during treatment or within 6 months of cessation of neoadjuvant/adjuvant treatment, this neoadjuvant/adjuvant treatment will be regarded as a line of systemic treatment. 5. At least one measurable/evaluable lesion by RECIST v1.1 as determined by local site investigator/radiology assessment within 28 days prior to first dose. NOTE: Lesions that have been previously irradiated may be considered evaluable provided there is evidence of disease progression following the completion of radiation therapy. 6. The HLA typing is HLA-A\*02:01 and/or HLA-A\*11:01. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Life expectancy ≥12 weeks. 9. The organ function level in the screening period must meet the following requirements (Laboratory data will not be valid if the patient has received growth factors or blood transfusion for prophylactic use within 7 days before the laboratory testing): * Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 * Platelet count （PLT）≥ 100,000 cells/mm3 * Hemoglobin（Hb）≥ 90 g/L * Serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) and Creatinine clearance rate (Cockcroft-Gault Formula) ≥ 50 mL/min * Serum total bilirubin ≤1.5 × ULN (or \< 3 × ULN in patients with Gilbert's syndrome or patients with liver metastasis) * Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (or ≤ 5.0 × ULN in patients with liver metastases) * Prothrombin time (PT), International normalized ratio (INR) ≤ 1.5 × ULN unless the patient is receiving anti-coagulant therapy * Urine routine/24-hour urine protein quantification: Urine protein qualitative ≤ 1+ (if urine protein qualitative ≥ 2+, then 24-hour urine protein \< 1 g can be enrolled) * Serum albumin ≥ 28 g/L. 10. Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies used to control cancer, all AEs have either returned to baseline or Grade 0\ 1, and stabilized. 11. Females of childbearing potential (WOCBP) must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening. Patients that are postmenopausal (with spontaneous amenorrhea for at least 24 months) or permanently sterilized can be considered as not having reproductive potential. Female patients of reproductive potential must agree to use highly effective contraception during and for 3 months after the last trial drug administration. 12. Non-sterile males who have female sexual partner(s) of childbearing potential must use highly effective form of birth control for the duration of the study, and for at least 3 months after the last trial drug administration. * A sterile male is defined as one for whom known azoospermia, in a semen sample examination, has been previously demonstrated as definitive evidence of infertility. * Males with known 'low sperm counts' (consistent with 'sub-fertility') are not to be considered sterile for purposes of this study.
Exclusion criteria
* To be eligible to participate in this study, a patient cannot meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events | From the signing of the ICF through 90 days after the last dose | Incidence and severity of adverse events (AEs), immune-related adverse events (irAEs), serious adverse events (SAEs) assessed by NCI-CTCAE v5.0, based on testing results of vital signs, physical examinations, 12-lead ECG and laboratory tests as well as participants reported adverse events. |
| PK parameter | 1 hour prior to the first and the sixth dose of IPM514, and 2h(±5min）、6h (±5min), 24h (±30min), 48h(±2h) hours post the first and the sixth dose of IPM514. | The time to peak (Tmax) will be analyzed by quantitative PCR (qPCR) for mRNA in peripheral blood |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DCR | up to 49 weeks | The DCR was defined as the percentage of participants who achieve CR, PR, and SD based on RECIST v 1.1 and iRECIST. |
| ORR | up to 49 weeks | The ORR was defined as the percentage of participants in the study whose best overall response was either CR or PR as assessed by investigators based on RECIST v 1.1 and iRECIST. |
| Number Of Participants With Anti-drug Antibodies (ADAs) | within 1 hour prior to the 1st, 6th and 8th administration of IPM514 | The immunogenicity will be evaluated via the incidence and titer of anti-drug antibodies (ADAs) |
| DOR | up to 49 weeks | DOR for responders (CR or PR) was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease or death for any cause, whichever occurred earlier. |
| PFS | up to 49 weeks | PFS was defined as the time from the date of first study dose to disease progression or death whichever occurs first. |
Outcome results
None listed