Description:
A Phase 1 Dose Escalation and Expansion Study of IMP7068 Monotherapy in Advanced Solid Tumors
Title
- Brief Title: The Safety and Pharmacokinetics Preliminary Efficacy of IMP7068 in Patients With Advanced Solid Tumors
- Official Title: A Phase 1, Open-Label, Multi-Center, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of the WEE1 Inhibitor IMP7068 Monotherapy in Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
IMP7068 - 101
- NCT ID:
NCT04768868
Conditions
Interventions
Drug | Synonyms | Arms |
---|
IMP7068 | | IMP7068 |
Purpose
A Phase 1 Dose Escalation and Expansion Study of IMP7068 Monotherapy in Advanced Solid Tumors
Detailed Description
This is A Phase 1, Open-Label, Multi-Center, Dose Escalation and Expansion Study to Evaluate
Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of the WEE1 Inhibitor IMP7068
Monotherapy in Patients with Advanced Solid Tumors
The study will include a dose-escalation stage and a dose-expansion stage. The
dose-escalation stage is designed to determine the maximum tolerated dose (MTD) and select
recommended Phase 2 dose (RP2D) of IMP7068 monotherapy. The dose-expansion stage will be
conducted with RP2D to further evaluate the preliminary anti-tumor activity, safety and
tolerability.
A total of approximately 150 patients will be enrolled in the study.
Approximately 50 patients will be enrolled into Part 1 dose escalation of IMP7068
monotherapy. A total of 100 patients each with advanced solid tumor will be evaluated in Part
2 dose-expansion of IMP7068 monotherapy.
Trial Arms
Name | Type | Description | Interventions |
---|
IMP7068 | Other | Part 1: Dose Escalation
The study will begin with open-label dose escalation in IMP7068 monotherapy treatment to determine the Maximum tolerated dose (MTD)
Part 2: Dose Expansion The dose-expansion stage will commence after the Recommended Phase 2 Dose (RP2D) is determined during the dose-escalation stage. A total of 100 patients each with advanced solid tumor who has exhausted available treatment options will be evaluated. | |
Eligibility Criteria
Key Inclusion Criteria:
1. The patient must voluntarily participate in this clinical study. Be willing and able
to provide written informed consent form (ICF) prior to any study activity.
2. Age ≥18 years on the day of signing the ICF (either from screening period for dose
escalation stage or from pre-screening period for dose expansion stage), males or
females.
3. The enrolled patients must have histologically or cytologically confirmed advanced
solid tumor that is refractory to standard treatment or for which no standard
treatment exists. The patients with known microsatellite-instability high (MSI- H) or
deficient in mismatch repair (dMMR) disease are required to have received prior PD
1/PD-L1 therapy; those with known NTRK fusion are required to have received an
approved TRK-inhibitor. The patients who are suitable for resection or other localized
therapy that is potentially curative are not eligible.
Key Exclusion Criteria:
1. Patients with active or untreated known CNS metastases and/or carcinomatous meningitis
should be excluded.
2. Patients with serious acute or chronic infections.
3. Patients who have received prescription or non-prescription drugs or other products
known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow
therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which
cannot be discontinued 7 days prior to Day 1 of dosing and withheld throughout the
study until 2 weeks after the last dose of IMP7068.
4. Patients who are participating in or have participated in a study of an
investigational agent and received study therapy or used an investigational device
within 28 days of the first dose of treatment.
5. Patients have not recovered (i.e., to Grade ≤1 or to baseline, as evaluated by
NCI-CTCAE Version 5.0) from prior anti-cancer therapy-induced AEs, except for
alopecia.
6. Patients who have undergone a major surgery or have undergone a radical radiotherapy
within 28 days prior to the study treatment, or have undergone a palliative
radiotherapy within 14 days prior to the study treatment, or have used a radioactive
drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.
7. Patients who are unable to swallow oral medications. Patients have gastrointestinal
illnesses that may clinically significantly affect the absorption of oral medication
IMP7068 at discretion of investigators.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part 1 Dose Escalation: Incidence of treatment emergent adverse events (TEAEs) |
Time Frame: | Day 1 through to 30 days after last dose (approximately 4 cycles (84 days plus 30 day follow-up )); Each cycle is 21 days |
Safety Issue: | |
Description: | Recommended Phase 2 Dose (RP2D) of IMP7068 monotherapy (selected by the safety monitoring committee (SMC) based on pharmacokinetics, target saturation at steady state, pharmacodynamics, safety, tolerability and preliminary anti-tumor effects of the dose range studied) |
Secondary Outcome Measures
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for maximum observed plasma drug concentration (Cmax) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for time to reach Cmax (Tmax) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for area under the plasma concentration-time curve from time zero to time tau (AUC0-tau) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses dose-normalized Cmax (Cmax [dn]) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for dose-normalized AUC0-tau (AUC0-tau [dn]) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses area under the plasma concentration time curve from time zero to infinity (AUC0-inf) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses terminal elimination half life (t1/2) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses apparent clearance (CL/F) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses apparent volume of distribution (Vz/F) |
Time Frame: | Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for Cmax |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for Tmax |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameters derived from plasma IMP7068 concentration following repeated oral doses for AUC0-last |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for AUC0-tau |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for minimum plasma concentration during the dosing interval (Cmin) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for Cmax (Rac_Cmax) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for AUC0-tau (Rac_AUC0-tau) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for Cmax (dn) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for AUC0-tau (dn) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses terminal elimination half life (t1/2) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses apparent clearance (CL/F) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses apparent volume of distribution (Vz/F) |
Time Frame: | Repeat-Dose Schedule 1 and Schedule 2: Each Cycle = 21 Days; Cycle 1 Day 1,2, 3, 4, 5, 6 and 8, Cycle 2 Day 1 and Cycle 3 Day 1; Repeat Dose Schedule 3: Cycle 1 Day 1, 2, 3, 4, 5 and 8, Cycle 2 Day 1 and Cycle 3 Day 1 |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Objective response rate (ORR): percentage of patients who had a best response |
Time Frame: | Within the first year: every 6 weeks, thereafter every 12 weeks to end of treatment (EOT) visit (approximately 84 days), documented disease progression, withdrawal of consent, loss to follow-up, death or termination of the study (whichever occurs first) |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Progression-free survival (PFS): duration of time from date of first dose to date of disease progression (according to RECIST v1.1) or death due to any cause, whichever comes first) |
Time Frame: | Within the first year: every 6 weeks (±7 days); thereafter: every 12 weeks (±7 days); or when clinically indicated (Approximately 1 year ) |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Overall survival (OS): time from date of first dose to death due to any cause |
Time Frame: | Every 12 weeks±14 days after the last dose, until up to 2 years, withdrawal of consent, loss to follow-up, death, or termination of the study, whichever occurs first |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Duration of response (DOR): duration of time a patient is evaluated as either complete response (CR) or partial response (PR) as best response until the first date that the criteria for progression are met, or death. |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 1 Dose Escalation: Disease control rate (DCR): proportion of patients who had a best response rating of complete response (CR) or partial response (PR), or stable disease (SD), which was maintained ≥6 weeks from Day 1 of Cycle 1 |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Progression-free survival (PFS) duration of time from date of first dose to date of disease progression (according to RECIST v1.1) or death due to any cause, whichever comes first) |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Duration of response (DOR) duration of time a patient is evaluated as either CR or PR as best response until the first date that the criteria for progression are met, or death |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Incidence of Treatment emergent adverse events (TEAE) |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Severity of Treatment emergent adverse events (TEAE) according to the NCI-CTCAE, version 5.0 |
Time Frame: | Day 1 through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Number of patients with changes in Vital Signs |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Part 2 Dose Expansion: Number of patients with changes in Physical Examination |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Number of patients with changes in single and triplicate 12-lead Electrocardiogram (ECG) |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Number of patients with changes in Laboratory Test - Serum chemistry |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Number of patients with changes in Laboratory Test - Hematology |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Number of patients with changes in Laboratory Test - Coagulation parameters |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Measure: | Number of patients with changes in Laboratory Test - Urinalysis |
Time Frame: | Screening (Day -28) through 30 days after last dose, estimated to be 5 months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Impact Therapeutics, Inc. |
Trial Keywords
- Breast Cancer
- Ovarian Cancer
- Prostate Cancer
- Pancreatic Cancers
Last Updated
July 27, 2021