A Phase I, Open-Label, Multicenter, Dose-Escalation And Cohort-Expansion Study Of IMM47 In Subjects With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- IMM47
- Conditions
- Oncology
- Sponsor
- ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
- Enrollment
- 48
- Locations
- 4
- Primary Endpoint
- DLTs
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a first-in-human (FIH), open-label, multi-center, phase I study to evaluate the safety, tolerance, pharmacokinetics (PK), immunogenicity, preliminary anti-tumor activity, pharmacodynamics, and biomarker activity of IMM47 monotherapy in subjects with advanced solid tumors.
Detailed Description
In phase Ia phase, approximately 17-48 eligible subjects with advanced solid tumors will be enrolled, and an accelerated titration method and the traditional "3+3" design method will be adopted to explore the safety, tolerability, PK, immunogenicity, and anti-tumor activity of 6 dose levels of IMM47: 5 μg/kg, 50 μg/kg, 250 μg/kg, 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg or higher, to determine the MTD and RP2D. Accelerated dose cohorts: At the dose cohorts of 5 μg/kg and 50 μg/kg, one subject will be enrolled at first, and the conventional "3+3" design will be altered and the additional 2 or 5 subjects would be enrolled if any ≥ Grade 2 drug related toxicities are observed during the first 28-day cycle (DLT observational period). "3+3" dose cohorts: Thereafter, at least three subjects will be enrolled in each dose cohort at the 250 μg/kg, 1.0 mg/kg, 3.0 mg/kg and 5.0 mg/kg dose levels sequentially. There will be a minimum interval of 48 hours between the 1st and 2nd subjects being dosed in each "3+3" dose cohort. If no DLTs occur in a dose cohort of 3 subjects during the first cycle (DLT observational period), 3 subjects will be enrolled at the next higher dose level. If 1 of 3 subjects in a cohort experiences a DLT, an additional 3 subjects will be enrolled at that dose level. If only 1 of 6 subjects experiences a DLT, then 3 subjects will be enrolled at the next higher dose level. If 2 or more subjects experienced DLTs within a cohort, dose escalation will be halted and 3 more subjects will be enrolled at the previous lower (tolerated) dose level until that cohort has 6 evaluable subjects. Depending on toxicity, the dose deescalation to an intermediate dose may occur. Higher doses than 5.0 mg/kg may be explored under the decision of Safety Review Committee (SRC). A total of 6 subjects must be enrolled at the MTD (or the highest dose studied where no more than 1 of 6 subjects experiences a DLT if the MTD is not identified) and evaluated at the end of Cycle 1 before any subject is dosed in the expansion cohorts. Continued dosing with IMM47 beyond the second cycle will be offered to subjects who do not experience disease progression or significant toxicity. Subjects who are benefiting from IMM47 will receive the treatment up to 12 cycles, at investigator's discretion. Subjects discontinuing the study treatment early for any reason will complete an end-of-treatment (EOT) visit within 30 (+7) days after the last dose, and a safety follow-up visit within 90 (±7) days after the last dose. If the subjects who achieve complete response (CR), partial response (PR), or stable disease (SD) with clinical benefit discontinue the investigational product, the follow-up visits will be completed every 12 weeks until disease progression, informed consent withdrawn by subject, death, or loss to follow-up, or end of study (whichever occurs first). Survival follow-up will be performed for a maximum of 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the time of signing the ICF.
- •With an expected life expectancy of ≥ 12 weeks.
- •With an ECOG performance status score of 0-
- •For phase Ia, subjects diagnosed histologically or cytologically with advanced solidtumors (preferred but not limited to ovarian, esophageal, breast, lung, colorectal, hepatocellular, pancreatic, urothelial, prostate, and head and neck cancers) that have failed previous standard treatments or no standard treatment is available.
- •The intervals for discontinuing the last anti-tumor therapy prior to the first dose of the investigational product are required as follows Subjects who previously received chemotherapeutic agents must have discontinued the drug for more than 3 weeks.
- •Subjects who previously received small-molecule targeted therapy must have discontinued treatment for more than 2 weeks or 5 half-lives of the drug (whichever is longer).
- •Subjects who previously received monoclonal antibodies (eg. CD20 antibody, PD-1/PD-L1 antibody) must have discontinued the treatment for more than 4 weeks.
- •Subjects who previously underwent palliative radiation therapy must have discontinued the treatment for more than 2 weeks.
- •With suitable organ and hematopoietic functions:
- •Neutrophil count ≥1.5 × 109/L. (no growth factor therapy within 4 weeks prior to Screening).
Exclusion Criteria
- •Subjects who previously received CD24 targeted therapy.
- •Prior allogeneic hematopoietic stem cell transplant or other organ transplants.
- •Subjects with known active central nervous system (CNS) metastases or primary CNS Lymphoma. Stable previously treated CNS metastases in subjects who are asymptomatic and have not been on corticosteroid therapy within 3 weeks prior to screening are not considered to be active.
- •Subjects in need of immediate cytoreduction therapy.
- •Significant medical disease or conditions, as assessed by the Investigators and Sponsor that would substantially increase the risk-benefit ratio of participating in the study. This includes but is not limited to:
- •Uncontrolled hypertension (systolic BP \> 160 mmHg or diastolic BP \> 90 mmHg), pulmonary hypertension, or unstable angina.
- •New York Heart Association (NYHA) Grade II or higher congestive heart failure. History of myocardial infarction, or bypass surgery or stent placement within 6 months prior to the first dose of the investigational product.
- •Severe arrhythmia requiring treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia that, according to the judgment of the investigators, do not affect the study).
- •QTc interval \> 450 ms for males and \> 470 ms for females (Fridericia's Formula).
- •History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to the first dose of investigational product.
Arms & Interventions
Dose escalation
It's a dose escalation to identify the Maximum Tolerated dose (MTD) , recommended Phase II dose (RP2D) of IMM47, an accelerated titration method and the traditional "3+3" design method will be adopted. IMM47 will be sequentially escalated at the dose of 5 μg/kg，50 μg/kg, 250 μg/kg，1.0 mg/kg，3.0 mg/kg and 5.0 mg/kg or higher dose levels, administered via intravenous infusion every 2 weeks in 28-day treatment cycles. The duration of the infusion is 120 min (± 10 min) for the 1st infusion and 60 min (± 5 min) for subsequent infusions.
Intervention: IMM47
Outcomes
Primary Outcomes
DLTs
Time Frame: Baseline up to 28 days after the first dose
Dose Limiting Toxicities
MTD(maximum tolerated dose)
Time Frame: From start of treatment to treatment termination visit, up to 48 weeks
To determine the maximum tolerated dose (MTD) of IMM47 in subjects with advanced solid tumors
adverse events (AEs)
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 48 weeks
Incidence and characteristics of adverse events (AEs)
RP2D (recommended Phase 2 dose)
Time Frame: From start of treatment to treatment termination visit, up to 48 weeks
To determine the recommended Phase 2 dose (RP2D) of IMM47 in in subjects with advanced solid tumors
serious adverse events (SAEs)
Time Frame: Baseline up to 30 days after the last dose of study drug, up to 48 weeks
Incidence and characteristics of serious adverse events (SAEs)
Secondary Outcomes
- Maximum Plasma Concentration (Cmax)(48 weeks of treatment cycles)
- Time to maximum concentration (Tmax)(48 weeks of treatment cycles)
- Elimination half-life (t1/2)(48 weeks of treatment cycles)
- Immunogenicity(48 weeks of treatment cycles)
- Overall Rate Response (ORR)(When the last subject enrolled completes approximately 48 weeks of treatment)
- Disease control rate (DCR)(When the last subject enrolled completes approximately 48 weeks of treatment)
- Duration of response (DoR)(When the last subject enrolled completes approximately 48 weeks of treatment)
- Progression-free Survival (PFS)(When the last subject enrolled completes approximately 48 weeks of treatment)
- AUC(0-tlast)(48 weeks of treatment cycles)
- AUC0-inf(48 weeks of treatment cycles)