A First-in-human Study of PARP1 Selective Inhibitor, IMP1734, in Participants With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06253130
• Other study ID #: EIK1003-001 (IMP1734-101)
• Secondary ID: 2023-509230-19
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 11, 2023
• Est. completion date: December 1, 2026

Study information

• Verified date: January 2024
• Source: Eikon Therapeutics
• Contact: Caroline Taromino
• Phone: (341) 777-0566
• Email: parpitrial[@]eikontx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: December 1, 2026
• Est. primary completion date: February 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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 HHR 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• IMP1734
PARP1 selective inhibitor

Locations

Country	Name	City	State
Australia	Peninsula and south eastern haematology and oncology group	Frankston	Victoria
Australia	Scientia Clinical Research Ltd	Randwick	New South Wales
Australia	Mater Cancer Care Centre, Mater Misericordiae Limited	South Brisbane	Queensland
Australia	Gold Coast Private Hospital	Southport	Queensland
Australia	Macquarie University	Sydney	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
United States	Advent Health Research Institute	Celebration	Florida
United States	Sarah Cannon Research Institute Health One	Denver	Colorado
United States	Sarah Cannon Research Institue Oncology	Nashville	Tennessee
United States	START - South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	START Mountain Region	West Valley City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Eikon Therapeutics	Impact Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Characterization of the pharmacodynamic changes due to IMP1734	Evaluation of serial pharmacodynamic changes across multiple doses of IMP1734	Through study completion, up to 3 years
Primary	Number of subjects with adverse events, treatment emergent adverse events or serious adverse events	Number of subjects reporting adverse events or serious adverse events which include any abnormal clinical events, laboratory assessments outside of normal clinical range, abnormal vital signs observed, and any abnormal ECG parameters	Consent to 30 + 7 days post last dose of IMP1734
Primary	Maxim Tolerated Dose or Recommended Dose for Expansion	Number of patients that experience a DLT or any toxicity which occurs from the time of the first dose of study drug until the end of cycle 1, which is deemed unrelated to the disease.	DLT period is from the first dose of the study drug until the last day of the first cycle
Secondary	Pharmacokinetic parameters of IMP1734	Peak plasma concentration (Cmax)	Through study completion, up to 3 years
Secondary	Pharmacokinetic parameters of IMP1734	Time to peak drug concentration (Tmax)	Through study completion, up to 3 years
Secondary	Pharmacokinetic parameters of IMP1734	Area under the curve (AUC) will be defined	Through study completion, up to 3 years
Secondary	Overall Response Rate	Percentage of participants who have CR/PR per RECIST v1.1,and/or CA125 response per GCIG criteria (ovarian cancer), and/or PSA response per PCWG3 criteria	Through study completion, up to 3 years