WEE1: The Safety and Pharmacokinetics Preliminary Efficacy of IMP7068 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
A Phase 1 Dose Escalation and Expansion Study of IMP7068 Monotherapy in Advanced Solid Tumors
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: IMP7068 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. |
Drug: IMP7068
To evaluate the safety tolerability, pharmacokinetics, and anti-tumor activity of the WEE1 inhibitor IMP7068 monotherapy in patients with advanced solid tumors
|
Outcome Measures
Primary Outcome Measures
- Part 1 Dose Escalation: Incidence of treatment emergent adverse events (TEAEs) [Day 1 through to 30 days after last dose (approximately 4 cycles (84 days plus 30 day follow-up )); Each cycle is 21 days]
- Part 1 Dose Escalation: Severity of treatment emergent adverse events (TEAEs), according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0 [Day 1 through to 30 days after last dose (approximately 4 cycles (84 days plus 30 day follow-up )); Each cycle is 21 days]
- Part 1 Dose Escalation: Number of patients with changes in Vital Signs [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in Physical Examination [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in single and triplicate 12-lead Electrocardiogram (ECG) [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in Laboratory Test - Serum chemistry [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in Laboratory Test - Hematology [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in Laboratory Test - Coagulation parameters [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Number of patients with changes in Laboratory Test - Urinalysis [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 1 Dose Escalation: Recommended Phase 2 Dose (RP2D) of IMP7068 monotherapy [Day 1 through to start of dose expansion phase (approximately 1 year)]
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)
- Part 2 Dose Expansion: Overall Response Rate (ORR) [Day 1 through 30 days after last dose, estimated to be 5 months]
Overall Response Rate (ORR) for all cohorts (percentage of patients who had a best response rating of complete response (CR) and partial response (PR), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, which was maintained ≥4 weeks)
Secondary Outcome Measures
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for maximum observed plasma drug concentration (Cmax) [Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses for time to reach Cmax (Tmax) [Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following single oral doses dose-normalized Cmax (Cmax [dn]) [Time Frame: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- 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: Single-Dose Phase: Day 1, 2, 3 and 4]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for Cmax [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for Tmax [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]
- Part 1 Dose Escalation: Pharmacokinetic parameters derived from plasma IMP7068 concentration following repeated oral doses for AUC0-last [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for AUC0-tau [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for minimum plasma concentration during the dosing interval (Cmin) [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for Cmax (Rac_Cmax) [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]
- 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) [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for Cmax (dn) [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]
- Part 1 Dose Escalation: Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses for observed accumulation ratio for AUC0-tau (dn) [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]
- 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) [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]
- Part 1 Dose Escalation: If the data are available, Pharmacokinetic parameter derived from plasma IMP7068 concentration following repeated oral doses apparent clearance (CL/F) [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]
- 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) [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]
- Part 1 Dose Escalation: Objective response rate (ORR): percentage of patients who had a best response [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)]
- 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) [Within the first year: every 6 weeks (±7 days); thereafter: every 12 weeks (±7 days); or when clinically indicated (Approximately 1 year )]
- Part 1 Dose Escalation: Overall survival (OS): time from date of first dose to death due to any cause [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]
- 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. [Day 1 through 30 days after last dose, estimated to be 5 months]
- 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 [Day 1 through 30 days after last dose, estimated to be 5 months]
- 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) [Day 1 through 30 days after last dose, estimated to be 5 months]
- 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 [Day 1 through 30 days after last dose, estimated to be 5 months]
- Part 2 Dose Expansion: Incidence of Treatment emergent adverse events (TEAE) [Day 1 through 30 days after last dose, estimated to be 5 months]
- Part 2 Dose Expansion: Severity of Treatment emergent adverse events (TEAE) according to the NCI-CTCAE, version 5.0 [Day 1 through 30 days after last dose, estimated to be 5 months]
- Part 2 Dose Expansion: Number of patients with changes in Vital Signs [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Part 2 Dose Expansion: Number of patients with changes in Physical Examination [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Number of patients with changes in single and triplicate 12-lead Electrocardiogram (ECG) [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Number of patients with changes in Laboratory Test - Serum chemistry [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Number of patients with changes in Laboratory Test - Hematology [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Number of patients with changes in Laboratory Test - Coagulation parameters [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
- Number of patients with changes in Laboratory Test - Urinalysis [Screening (Day -28) through 30 days after last dose, estimated to be 5 months]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
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.
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Age ≥18 years on the day of signing the ICF, males or females. Only for Korea, Age ≥19 years on the day of signing the ICF.
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The enrolled patients must have histologically or cytologically confirmed advanced solid tumor that is refractory/intolerant 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:
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Patients with active or untreated known CNS metastases and/or carcinomatous meningitis should be excluded.
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Patients with serious acute or chronic infections.
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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.
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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.
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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, anorexia or CTCAE grade 2 peripheral neuropathy.
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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.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emory University Hospital | Atlanta | Georgia | United States | 30322 |
| 2 | University of Kansas Clinical Research Center | Fairway | Kansas | United States | 66205 |
| 3 | Norton Cancer Institute | Louisville | Kentucky | United States | 40202 |
| 4 | Comprehensive Cancer Centers of Nevada | Las Vegas | Nevada | United States | 89169 |
| 5 | Mary Crowley Cancer Research | Dallas | Texas | United States | 75230 |
| 6 | Next Oncology | San Antonio | Texas | United States | 78229 |
| 7 | Wuhan Union Hospital | Wuhan | HB | China | 430030 |
| 8 | West China 2nd University Hospital | Chengdu | Sichuan | China | 610066 |
| 9 | Beijing Cancer Hospital | Beijing | China | 100142 | |
| 10 | Fudan University Shanghai Cancer Center | Shanghai | China | 201321 | |
| 11 | Chang Gung Medical Foundation - Linkou Branch | Taoyuan | TW | Taiwan | |
| 12 | China Medical University Hospital | Taichung | Taiwan | 40447 | |
| 13 | National Cheng Kung University Hospital | Tainan | Taiwan | 704 | |
| 14 | Chi Mei Hospital, Liouying | Tainan | Taiwan | 73657 | |
| 15 | National Taiwan University Hospital | Taipei | Taiwan |
Sponsors and Collaborators
- Impact Therapeutics, Inc.
- Covance
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMP7068 - 101