Clinical trial NCT06253130: A First-in-human Study of PARP1 Selective Inhibitor, IMP1734, in Participants With Advanced Solid Tumors
Official title: A First-in-human, Phase 1/2, Open-label, Multi-center, Dose-escalation, Dose-optimization, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of PARP1 Selective Inhibitor, IMP1734, as Monotherapy in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Keywords: EIK1003
EIK1003-001
IMP1734
Lead sponsor: Eikon Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Impact Therapeutics, Inc.
First posted: 2024-02-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the preliminary efficacy of IMP1734 in patients with recurrent advanced/metastatic breast cancer, ovarian cancer and metastatic castrate resistant prostate cancer (mCRPC) with deleterious/suspected deleterious mutations of select homologous recombination repair (HRR) genes.

Detailed description: This study will evaluate the safety, tolerability and preliminary efficacy of IMP1734 as monotherapy in patients with recurrent, advanced/metastatic solid tumors. The study consists of 3 parts: Dose escalation, Dose Optimization and Dose expansion.

In dose escalation (Part1), the study will identify the maximum tolerated dose (MTD) or maximum achievable dose (MAD) in solid tumor.

In dose optimization (Part 2), the study will further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of select doses of IMP1734.

In dose expansion (Part 3) the recommended dose escalation (RDE) of IMP1734 monotherapy will be evaluated in patients with recurrent, advanced/metastatic breast cancer, ovarian cancer and mCRPC with deleterious/suspected deleterious mutations of select homologous recombination repair (HRR) gene mutations.

Eligibility criteria: Key Inclusion Criteria

* Breast cancer; must have received at least one prior chemotherapy in neoadjuvant/adjuvant/metastatic setting, must have received hormonal therapy if HR+,
* HGSOC or high grade endometrioid EOC, fallopian tube or primary peritoneal cancer; must have received at least one prior platinum-based chemotherapy for advanced disease
* mCRPC with ongoing ADT, must have received NHA and up to 1 prior line of taxane chemotherapy
* Age ≥ 18 years at the time of informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Adequate organ function
* Life expectancy ≥ 12 weeks
* Should have evaluable disease as defined by RECIST1.1 and/or CA125 or PSA
* Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception from study entry up to 6 months after the last dose of IMP1734
* deleterious or suspected deleterious germline or somatic mutations of select HRR genes
* up to 1 prior line of PARP inhibitor containing treatment

Key Exclusion Criteria:

* Any investigational or approved anti-cancer therapies administered within 28 days/ before the first dose of IMP1734
* Have received prior PARP1 selective inhibitors
* Mean resting QTcF \> 470 ms or QTcF \< 340 ms
* Active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Infections

  - An active hepatitis B/C infection
* Any known predisposition to bleeding
* Unable to swallow oral medications OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition that might impair the bioavailability

Primary outcomes:
measure: Number of subjects with adverse events, treatment emergent adverse events or serious adverse events
timeFrame: Consent to 30 + 7 days post last dose of IMP1734
measure: Maxim Tolerated Dose or Recommended Dose for Expansion
timeFrame: DLT period is from the first dose of the study drug until the last day of the first cycle
Secondary outcomes:
measure: Pharmacokinetic parameters of IMP1734
timeFrame: Through study completion, up to 3 years
measure: Pharmacokinetic parameters of IMP1734
timeFrame: Through study completion, up to 3 years
measure: Pharmacokinetic parameters of IMP1734
timeFrame: Through study completion, up to 3 years
measure: Overall Response Rate
timeFrame: Through study completion, up to 3 years
Other outcomes:
measure: Characterization of the pharmacodynamic changes due to IMP1734
timeFrame: Through study completion, up to 3 years
Locations:
city: Irvine
country: United States
facility: University California Irvine
state: California
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute Health One
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Celebration
country: United States
facility: Advent Health Research Institute
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University - Siteman Cancer Center
state: Missouri
city: Ithaca
country: United States
facility: Cayuga Medical Center
state: New York
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC) - Hollings CC
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institue Oncology
state: Tennessee
city: San Antonio
country: United States
facility: START - South Texas Accelerated Research Therapeutics
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Cancer Care Centre, Mater Misericordiae Limited
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Private Hospital
state: Queensland
city: Sydney
country: Australia
facility: Macquarie University
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Frankston
country: Australia
facility: Peninsula and south eastern haematology and oncology group
state: Victoria
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Seongnam-si
country: Korea, Republic of
facility: CHA Bundang Medical Center, CHA University
state: Gyeonggi-Do
city: Incheon
country: Korea, Republic of
facility: Gachon University - Gil Medical Center
state: Namdong-gu
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
Study officials:
affiliation: Eikon Therapeutics
name: Viola Chen, MD
role: STUDY_DIRECTOR
References: