This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors and with ES-SCLC who develops disease progression after 1L platinum-based regimen.
This study will be conducted in two parts. Part I of the study will be dose escalation evaluation to determine the MTD and/or recommended phase 2 dose(RP2D) of IMP4297 in combination with temozolomide. Part II of the study will be conducted in two expansion cohorts (sensitive ES-SCLC cohort and resistant ES-SCLC cohort) to further evaluate the anti-tumor activity, safety and tolerability of this regimen in ES-SCLC patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
59
The dose levels will be escalated following a modified 3+3 dose escalation scheme.
GenHarp Clinical Solutions
Evergreen Park, Illinois, United States
Gabrail Cancer Researh Center
Part I: Dose Escalation safety and tolerability
TEAEs, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests (including serum chemistry, hematology, and urinalysis, coagulation), etc.
Time frame: From signing ICF until safety follow-up
Part I: Dose Escalation MTD
the maximum tolerated dose:the highest dose level at which \<1/3 patients experience DLT
Time frame: from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)
Part I: Dose Escalation RP2D
the recommended phase 2 dose
Time frame: from the initiation of study drugs until the end of dose escalation phase(approximately 1 year)
Part II: Dose Expansion Overall Response Rate (ORR)
the percentage of patients who had a best response rating of CR and PR which was maintained ≥4 weeks from the first manifestation of that rating.
Time frame: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study, which occurs first.
Part I: Dose Escalation plasma PK profile of IMP4297 and temozolomide
To characterize the plasma PK profile of IMP4297 and temozolomide via population PK (popPK) modeling
Time frame: Cycle 1 Day 1, Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit
Part I: Dose Escalation anti-tumor activity
Progression-free survival (PFS),Duration of response (DoR),Disease control rate (DCR)
Time frame: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study
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Canton, Ohio, United States
Mark H. Zangmeister Center
Columbus, Ohio, United States
Sarah Cannon Research Institute - Tennessee Oncology
Tennessee City, Tennessee, United States
Border Medical Oncology
Albury, New South Wales, Australia
Blacktown Hospital
Blacktown, New South Wales, Australia
Orange Hospital
Orange, New South Wales, Australia
Peninsula Health Frankston Hospital
Frankston, Victoria, Australia
Beijing Cancer Hospital
Beijing, China
Jilin Cancer Hospital
Jilin City, China
...and 11 more locations
Part I: Dose Escalation,effect of IMP4297 on QT interval
Correlation between IMP4297 plasma concentration and QT interval
Time frame: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit
Part II: Dose Expansion safety and tolerability
TEAE, vital signs, physical examinations, ECG, laboratory tests (including serum chemistry, hematology, urinalysis and coagulation), etc.
Time frame: From signing ICF until safety follow-up
Part II: Dose Expansion anti-tumor activity
progression-free survival (PFS ),duration of response (DoR),Disease control rate (DCR),overall survival (OS)
Time frame: from the initiation of study drugs until documented disease progression, withdrawal of consent, loss to follow-up, death, initiation of new anti-cancer treatment or termination of study
Part II: Dose Expansion PK profile of IMP4297 and temozolomide
PK parameters derived from IMP4297 and temozolomide plasma concentration data
Time frame: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,Any cycle after cycle 2,unscheduled visit
Part II: Dose Expansion effect of IMP4297 on QT interval
Correlation between IMP4297 plasma concentration and QT interval
Time frame: Cycle 1 Day 1,Cycle 1 Day 15,Cycle 2 Day 1,CnD1,EOT, unscheduled visit