The Safety and Pharmacokinetics Preliminary Efficacy of IMP7068 in Patients With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

— WEE1  

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04768868
• Other study ID #: IMP7068 - 101
• Status: Recruiting
• Phase: Phase 1
• Start date: February 25, 2021
• Est. completion date: August 30, 2023

Study information

• Verified date: February 2023
• Source: Impact Therapeutics, Inc.
• Contact: Jian Wang
• Phone: +86 18613056501
• Email: Jian.wang[@]impacttherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase 1 Dose Escalation and Expansion Study of IMP7068 Monotherapy in Advanced Solid Tumors

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: August 30, 2023
• Est. primary completion date: April 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, males or females. Only for Korea, Age =19 years on the day of signing the ICF.

3. 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:

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, anorexia or CTCAE grade 2 peripheral neuropathy.

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• IMP7068
To evaluate the safety tolerability, pharmacokinetics, and anti-tumor activity of the WEE1 inhibitor IMP7068 monotherapy in patients with advanced solid tumors

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	West China 2nd University Hospital	Chengdu	Sichuan
China	Fudan University Shanghai Cancer Center	Shanghai
China	Wuhan Union Hospital	Wuhan	HB
Taiwan	China Medical University Hospital	Taichung
Taiwan	Chi Mei Hospital, Liouying	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou Branch	Taoyuan	TW
United States	Emory University Hospital	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Next Oncology	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Impact Therapeutics, Inc.	Covance

Countries where clinical trial is conducted

United States,  China,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Part 1 Dose Escalation: Recommended Phase 2 Dose (RP2D) of IMP7068 monotherapy	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)	Day 1 through to start of dose expansion phase (approximately 1 year)
Primary	Part 2 Dose Expansion: Overall Response Rate (ORR)	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)	Day 1 through 30 days after last dose, estimated to be 5 months
Secondary	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)
Secondary	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)
Secondary	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 )
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2 Dose Expansion: Incidence of Treatment emergent adverse events (TEAE)		Day 1 through 30 days after last dose, estimated to be 5 months
Secondary	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