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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 350
- Locations
- 16
- Primary Endpoint
- 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
Study Overview
Brief Summary
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 140-350 patients will be enrolled in the study.
Approximately 60-100 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
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
- •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.
- •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.
Exclusion Criteria
- •Patients with active or untreated known CNS metastases and/or carcinomatous meningitis should be excluded.
- •Patients with serious acute or chronic infections.
- •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 IMP
- •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.
- •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.
- •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.
- •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.
Arms & Interventions
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.
Intervention: IMP7068 (Drug)
Outcomes
Primary Outcomes
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
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
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
Part 1 Dose Escalation: Recommended Phase 2 Dose (RP2D) of IMP7068 monotherapy
Time Frame: 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)
Time Frame: 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 Outcomes
- 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: 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 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 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 ))
- Plasma Concentration of IMP7068(Day -7 to repeat dose Day 1; postdose at multiple time points from Day 1 to Day 21 in Cycle 1 (Cycle 1 = 21 days), Day 1 on Cycle 2 (Cycle 2 onwards = 21 day-cycles) and subsequent cycles (Up to 26 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 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: 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)