A Phase I/II, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetic, Pharmacodynamic Characteristics and Initial Anti-tumor Activity of IPG1094 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- IPG1094
- Conditions
- Solid Tumor
- Sponsor
- Nanjing Immunophage Biotech Co., Ltd
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Primary endpoint
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
Brief Summary
This is a phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics and initial anti-tumor activity of IPG1094 in patients with advanced solid tumors. The study will be conducted in two parts: dose escalation phase (Part A) and expansion phase (Part B).
Detailed Description
Part A: In this phase, dose escalation will start from 200 mg and the present 2 dose cohorts are 200 mg BID and 250 mg BID. Up to 12 subjects are expected to be enrolled in this part. In each cohort, all subjects will receive a single oral dose of IPG1094, followed by a 3-day single-dose PK study period. If no significant toxicity occurs, subjects will receive consecutive daily doses (QD, 28 days/cycle) until disease progression, death, unacceptable toxicity, or withdrawal of informed consent (whichever comes first). The DLT evaluation period includes the single-dose PK study period and the first cycle of treatment (within 31 days after the first dose). The remaining subjects within the same cohort will be dosed if no significant safety signals are identified in the first subject in 3 days. Starting at 200 mg cohort, 3 subjects will be enrolled initially at each subsequent dose cohort in accordance with the 3+3 dose-escalation design. After 3 subjects in each cohort completed DLT evaluation, the Safety Monitoring Committee (SMC) will review all available safety and PK/PD data from all treated subjects (DLT evaluable and non-DLT evaluable subjects), taking into consideration the dose-assignment recommendation based on 3+3 decision rule (as described in the table below), to make the recommendation on the conduct of the study including the dose level and dose schedule for subsequent subjects. Part B: After all subjects in Part A completed DLT evaluations, the SMC will review all available safety, PK/PD and efficacy data from all treated subjects, to recommend 1 dose level for Part B. Phase B is an expansion study to evaluate the anti-tumor efficacy and safety of IPG1094 in patients with several types of solid tumors, including but not limited to small cell lung cancer, triple-negative breast cancer, head and neck cancer, and melanoma (specific tumor types will depend on the results of Part A), with 12 subjects in each cohort. A sparse sampling approach for PK with 3 to 4 time points on Day 1 and 3 to 4 time points on Day 28 of Cycle 1, and pre-dose on Day 1 of Cycle 2 and every other cycle thereafter (for example, C4D1, C6D1, C8D1) to allow for population PK and exposure-response (efficacy and safety endpoints) analyses. Subjects will receive consecutive doses (at the recommended schedule, 28 days/cycle) until disease progression, death, unacceptable toxicity, or withdrawal of informed consent (whichever comes first). The RP2D will be established by taking into consideration of the PK/PD profiles, safety and efficacy data from both Part A and Part B. The anti-tumor activity will be evaluated according to the response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Efficacy assessments will be performed at the screening (within 28 days prior to first administration) and every 2 cycles (8 weeks±7 days) until disease progression, death, withdrawal of informed consent, or study discontinuation. Subjects who discontinue treatment for reasons other than disease progression or death should continue with imaging assessments per protocol-defined schedule until disease progression, death, starting new anti-tumor therapies or withdrawal of informed consent, whichever occurs first. Subjects may be contacted via phone for vital status every 3 months post the last dose until death, withdrawal of informed consent, loss to follow-up or study discontinuation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must meet all of the following criteria to be included in the study:
- •Male or female aged ≥ 18 years.
- •Subjects must have a histological diagnosis of locally advanced or metastatic malignant solid tumors, and that is not amenable to curative surgical and/or locoregional therapies;
- •Subjects must have a histological diagnosis of locally advanced or metastatic malignant solid tumors, and that is not amenable to curative surgical and/or locoregional therapies (tumor types in Part B will include but not limited to small cell lung cancer, triple-negative breast cancer, head and neck cancer, and melanoma).
- •Subjects must have failed or have been intolerant to established standard therapies, or standard therapies did not exist or were no longer effective for a given tumor type, or in the opinion of the investigator have been considered ineligible for a particular form of standard therapy on medical grounds.
- •Subjects must have at least one evaluable lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Life expectancy ≥ 12 weeks.
- •Subjects must have adequate organ and bone marrow function (no hematopoietic growth factor, blood transfusion, or platelet therapy within 2 weeks before the screening and during the screening):
- •Complete blood count (CBC): neutrophils ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L, hemoglobin ≥ 9.0 g/dL.
Exclusion Criteria
- •Subjects who meet any of the following criteria will be excluded from the study:
- •Subjects who received anti-tumor therapy (except for mitomycin, nitrosourea, and fluorouracil oral drugs) within 4 weeks before the first dose, including but not limited to chemotherapy, radiotherapy (palliative radiotherapy is completed at least 2 weeks before the first dose can be enrolled), targeted therapy or immunotherapy.
- •Note: Mitomycin and nitrosourea have been treated within 6 weeks after the last dose; oral fluorouracil such as tegafur and capecitabine has been treated within 2 weeks after the last dose.
- •Subjects who have previous toxicity of anti-tumor therapy that has not been returned to level 0 or
- •(Alopecia, chemotherapy-induced peripheral neurotoxicity and ototoxicity ≤ Grade 2 can be enrolled).
- •Subjects who received CYP3A4 strong inhibitors or CYP3A4 strong inducers (see https://drug-interactions.medicine.iu.edu/MainTable.aspx) within 14 days prior to the first dose and the subjects who need to continue using these drugs throughout the study.
- •Subjects who received clinical intervention for biliary obstruction 14 days prior to the first dose or the investigator judges that the symptoms had not resolved or required anti-infective treatment.
- •Subjects who had clinically uncontrollable pleural effusion, ascites, or pericardial effusion within 2 weeks prior to the first dose.
- •Subjects who have symptomatic brain metastases or spinal cord compression. Subjects who have previously treated for brain metastases, if the clinical condition is stable and imaging evidence does not show disease progression within 4 weeks prior to the first dose and do not need corticosteroid treatment within 2 weeks prior to the first dose, can be enrolled.
- •Subjects who have active bacterial or fungal infections (≥ Grade 2) that required systemic treatment within 14 days prior to the first dose.
Arms & Interventions
Cohort 1 (200 mg BID)
Starting at 200mg BID cohort, 3 subjects will be enrolled. After 3 subjects completed DLT evaluation, the Safety Monitoring Committee (SMC) will review all available safety and PK/PD data from all treated subjects (DLT evaluable and non-DLT evaluable subjects), taking into consideration the dose-assignment recommendation based on 3+3 decision rule , to make the recommendation on the conduct of the study including the dose level and dose schedule for subsequent subjects.
Intervention: IPG1094
Cohort 2 (250 mg BID)
Starting at 250 mg BID cohort, 3 subjects will be enrolled. After 3 subjects completed DLT evaluation, the Safety Monitoring Committee (SMC) will review all available safety and PK/PD data from all treated subjects (DLT evaluable and non-DLT evaluable subjects), taking into consideration the dose-assignment recommendation based on 3+3 decision rule , to make the recommendation on the conduct of the study including the dose level and dose schedule for subsequent subjects.
Intervention: IPG1094
Cohort 3 (NSCLC)
Phase B is an expansion study to evaluate the anti-tumor efficacy and safety of IPG1094 in patients with non small cell lung cancer (specific tumor types will depend on the results of Part A), with 12 subjects enrolled. A sparse sampling approach for PK with 3 to 4 time points on Day 1 and 3 to 4 time points on Day 28 of Cycle 1, and pre-dose on Day 1 of Cycle 2 and every other cycle thereafter (for example, C4D1, C6D1, C8D1) to allow for population PK and exposure-response (efficacy and safety endpoints) analyses.
Intervention: IPG1094
Cohort 4 (TNBC)
Phase B is an expansion study to evaluate the anti-tumor efficacy and safety of IPG1094 in patients with triple-negative breast cancer (specific tumor types will depend on the results of Part A), with 12 subjects enrolled. A sparse sampling approach for PK with 3 to 4 time points on Day 1 and 3 to 4 time points on Day 28 of Cycle 1, and pre-dose on Day 1 of Cycle 2 and every other cycle thereafter (for example, C4D1, C6D1, C8D1) to allow for population PK and exposure-response (efficacy and safety endpoints) analyses.
Intervention: IPG1094
Cohort 5 (head and neck cancer)
Phase B is an expansion study to evaluate the anti-tumor efficacy and safety of IPG1094 in patients with head and neck cancer (specific tumor types will depend on the results of Part A), with 12 subjects enrolled. A sparse sampling approach for PK with 3 to 4 time points on Day 1 and 3 to 4 time points on Day 28 of Cycle 1, and pre-dose on Day 1 of Cycle 2 and every other cycle thereafter (for example, C4D1, C6D1, C8D1) to allow for population PK and exposure-response (efficacy and safety endpoints) analyses.
Intervention: IPG1094
Cohort 6 (brain glioma)
Phase B is an expansion study to evaluate the anti-tumor efficacy and safety of IPG1094 in patients with brain glioma (specific tumor types will depend on the results of Part A), with 12 subjects enrolled. A sparse sampling approach for PK with 3 to 4 time points on Day 1 and 3 to 4 time points on Day 28 of Cycle 1, and pre-dose on Day 1 of Cycle 2 and every other cycle thereafter (for example, C4D1, C6D1, C8D1) to allow for population PK and exposure-response (efficacy and safety endpoints) analyses.
Intervention: IPG1094
Outcomes
Primary Outcomes
Primary endpoint
Time Frame: Up to 8 months
recommended phase 2 dose (RP2D)
Secondary Outcomes
- Secondary endpoint 1(Up to 6-8 months)
- Secondary endpoint 2(Up to 6-8 months)