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

Overview

This study investigates the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of EIK1003 in participants with advanced solid tumors.

Detailed description

This study will evaluate the safety, tolerability and preliminary efficacy of IMP1734 as monotherapy in patients with recurrent, advanced/metastatic solid tumors. This study includes 2 parts: Part 1 and Part 2. Part 1 includes a monotherapy dose escalation of EIK1003 followed by combination dose escalations in metastatic prostate cancer (mPC), ovarian and breast cancer.

Part 1, dose escalation, the study will identify the maximum tolerated dose (MTD) or maximum achievable dose (MAD) in solid tumor.

Part 2 will explore dose optimization with selection of an optimal dose for future clinical development of EIK1003.

Interventions

• Drug IMP1734
  PARP1 selective inhibitor

Primary outcome measures

• Number of subjects with adverse events, treatment emergent adverse events or serious adverse events [Time frame: Consent to 30 + 7 days post last dose of IMP1734]
• Maxim Tolerated Dose or Recommended Dose for Expansion [Time frame: DLT period is from the first dose of the study drug until the last day of the first cycle]

Secondary outcome measures (4)

• Pharmacokinetic parameters of IMP1734 [Time frame: Through study completion, up to 3 years]
• Pharmacokinetic parameters of IMP1734 [Time frame: Through study completion, up to 3 years]
• Pharmacokinetic parameters of IMP1734 [Time frame: Through study completion, up to 3 years]
• Overall Response Rate [Time frame: Through study completion, up to 3 years]

Eligibility criteria

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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 23 centers

• The University of Arizona Cancer Center — Tucson
• University of Arkansas Winthrop P. Rockefeller Cancer Institute — Little Rock
• Hoag Health Center Irvine — Irvine
• University California Irvine — Irvine
• Sharp Memorial Hospital — San Diego
• University of California San Francisco (UCSF) — San Francisco
• Sarah Cannon Research Institute Health One — Denver
• Smilow Cancer Hospital at Yale New Haven — New Haven
• … and 15 more centers

Spain · 10 centers

• Hospital Universitari Parc Taulí — Sabadell
• Hospital Clinico San Carlos — Madrid
• Clínica Universidad de Navarra - Hospital — Pamplona
• Hospital del Mar — Barcelona
• Vall d'Hebron Institute of Oncology — Barcelona
• Fundacion MD Anderson Cancer Center — Madrid
• START Madrid Fundación Jiménez Díaz — Madrid
• START-CIOCC HM Sanchinarro Hospital — Madrid
• … and 2 more centers

China · 8 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• Shandong Cancer Hospital — Jinan
• Sir Run Run Shaw Hospital Zhejiang University School of Medicine — Hangzhou
• Chongqing University Cancer Hospital — Chongqing
• Fujian Cancer Hospital — Fuzhou
• Zhejiang Cancer Hospital — Hangzhou
• Fudan University Shanghai Cancer Center — Shanghai

Australia · 6 centers

• Scientia Clinical Research Ltd — Randwick
• Mater Cancer Care Centre, Mater Misericordiae Limited — South Brisbane
• Gold Coast Private Hospital — Southport
• Macquarie University — Sydney
• Princess Alexandra Hospital — Woolloongabba
• Peninsula and south eastern haematology and oncology group — Frankston

Canada · 3 centers

• Cross Cancer Institute — Edmonton
• Sunnybrook Research Institute — Toronto
• Princess Margaret Cancer Centre-University Health Network — Toronto

France · 3 centers

• Hospices Civils de Lyon - CHU Lyon Sud — Pierre-Bénite
• CLCC François Baclesse — Caen
• Institut Gustave Roussy — Villejuif

South Korea · 3 centers

• CHA Bundang Medical Center, CHA University — Seongnam-si
• Gachon University - Gil Medical Center — Incheon
• Severance Hospital, Yonsei University Health System — Seoul

Denmark · 1 center

• Righospitalet — Copenhagen

Identifiers

NCT: NCT06253130 · EIK1003-001 (IMP1734-101) · 2023-509230-19

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗