Evaluation of EIK1004 Bis-Tartrate Monotherapy in Advanced Solid Tumors: A Phase 1/2 Dose-Escalation and Dose-Optimization Study

Trial ID: 2024-520395-99-00
Protocol: EIK1004-001
Sponsor: Eikon Therapeutics Inc.

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Diseases & Conditions

Neoplasm

Objectives

The primary objective of this study is to evaluate the **safety** and **tolerability** of EIK1004 as monotherapy in participants with advanced solid tumors. This evaluation aims to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended dose for expansion (RDE) in Part 1, as well as to assess safety and tolerability in Part 2. Understanding the safety profile is crucial for ensuring patient safety and optimizing therapeutic dosing in clinical practice.

Secondary objectives include:

Characterizing the plasma **pharmacokinetic** profile of single and multiple doses of EIK1004 in both Part 1 and Part 2, which is essential for understanding the drug's absorption, distribution, metabolism, and excretion.
Assessing the preliminary **antitumor** activity of EIK1004 as monotherapy in Part 1 and Part 2, which provides early insights into the potential efficacy of the treatment in reducing tumor burden.

Participants

The clinical trial involves a total of **9 participants** diagnosed with **advanced solid tumors**. The study population includes both male and female subjects, aged **18 years and older**, with a focus on individuals who have a confirmed diagnosis of advanced, recurrent, or metastatic cancers such as endometrioid epithelial ovarian cancer, fallopian tube or primary peritoneal cancer, HER2-negative adenocarcinoma of the breast, metastatic castration-resistant prostate cancer, and advanced pancreatic ductal adenocarcinoma. Participants are required to have deleterious or suspected deleterious germline or somatic mutations in specific genes, including BRCA1, BRCA2, PALB2, RAD51B, RAD51C, or RAD51D. The trial population was selected based on their ability to comply with study procedures, adequate organ function, and an **ECOG Performance Status** of 0 to 1, indicating a relatively stable general health status. Participants must have a life expectancy of at least 12 weeks and documented radiological progressive cancer before study entry. Lifestyle considerations such as diet and physical activity are not specified, but participants must not be in lactation and should use highly effective contraceptive methods if of childbearing potential. The trial includes a vulnerable population, ensuring comprehensive safety and ethical considerations are in place.

Plans and Procedures

The clinical trial is designed as a **Phase 1/2**, open-label, multicenter study to evaluate the safety, tolerability, and activity of **EIK1004** as monotherapy in participants with advanced solid tumors. The trial employs a dose-escalation and dose-optimization approach to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended dose for expansion (RDE). The study is not randomized or blinded, allowing for direct observation of the effects of the investigational product. The trial is expected to commence recruitment on July 15, 2025, and conclude by July 30, 2027, with the overall duration spanning approximately two years.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, medical history, and organ function. The screening process ensures that participants have advanced solid tumors and meet other inclusion criteria, such as having deleterious mutations in specific genes. Following successful screening, participants will enter the treatment phase, where they will receive **EIK1004** tablets orally. The study includes multiple follow-up visits to monitor safety, tolerability, and pharmacokinetic parameters, as well as to assess primary endpoints such as dose-limiting toxicities and adverse events. Secondary endpoints include objective response, disease control, and clinical benefit.

The expected length of participant involvement varies depending on individual response and tolerance to the treatment, but it generally extends throughout the trial duration. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or disease progression that necessitates alternative treatment. The end-of-study visit will involve a comprehensive evaluation of the participant's health status and the collection of final data to contribute to the overall analysis of the trial outcomes.

Treatment

The clinical trial involves the administration of **EIK1004** as the experimental medication. **EIK1004** is provided in two dosage forms: 20 mg and 5 mg tablets. The active substance in both formulations is **EIK1004 BIS-TARTRATE**, a chemical compound developed by EIKON THERAPEUTICS, INC. The pharmaceutical form of the medication is a tablet, and it is administered orally. The trial is designed to evaluate the safety, tolerability, and activity of **EIK1004** as a monotherapy in participants with advanced solid tumors. The dosing schedule involves dose-escalation and dose-optimization phases to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and the recommended dose for expansion (RDE).

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of **EIK1004**. Participant compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol. The trial does not include any pediatric formulations, and the medication is not classified as an orphan drug. The study aims to gather comprehensive data on the effects of **EIK1004** in the specified patient population, contributing to the understanding of its potential therapeutic benefits and safety profile.

Efficacy

Efficacy in the clinical trial evaluating EIK1004 as monotherapy for participants with advanced solid tumors will be assessed using several parameters. Primary endpoints include **dose-limiting toxicities (DLTs)** and adverse events (AEs), which will be monitored to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended dose for expansion (RDE). Secondary endpoints will focus on pharmacokinetic (PK) parameters derived from plasma concentration data of EIK1004 and/or its metabolites following both single and multiple oral doses. Additionally, objective response (OR), disease control (DC), duration of response (DOR), time to response (TTR), percentage change from baseline in the sum of target lesions, clinical benefit (CB), and time to central nervous system (CNS) progression will be evaluated.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Participants must voluntarily participate and comply with study procedures
Participants must be ≥ 18 years of age
Participants must have 1 of the following: a. Confirmed advanced/recurrent/metastatic, endometrioid EOC, fallopian tube or primary peritoneal cancer (Cohorts-1A/C, Pt2/3), and: i. Must received ≥ 1 prior chemotherapy for advanced disease ii. Should have evaluable disease as defined: a. ≥ 1 measurable lesion per RECIST v1.1 and/or b. CA125 evaluable b. Confirmed advanced/recurrent/metastatic HER2-neg adenocarcinoma of the breast and (Pt 1 and 2): i. Must have received ≥ 1 prior chemotherapy ii. Participants with HR+ must have received hormonal therapy iii. Should have evaluable disease defined as ≥ 1 measurable lesion c. Confirmed adenocarcinoma of mCRPC (Pt1): i. mCRPC: With ongoing ADT within 28 days before study start. Participants receiving ADT should continue treatment during the study ii. Prior therapies: a. Must have received a novel hormonal agent b. Must have received up to 1 prior taxane based chemotherapy/ineligible for chemotherapy iv. Should have evaluable disease defined as: a) ≥ 1 measurable lesion per RECIST v1.1, AND/OR b) ≥ 1 evaluable lesion documented by positive bone scan c) PSA evaluable defined as a serum PSA ≥ 1 ng/mL during screening based on prostate working group 3 criteria. d) Histologically/cytologically confirmed advanced/recurrent/ mPDAC (Part 1) i. Must have received an appropriate prior regimen per Investigator ii. Should have evaluable disease defined as ≥ 1 measurable lesion per RECIST v1.1
Participants are required to have deleterious or suspected deleterious germline or somatic mutations of one of the following genes: BRCA1, BRCA2, PALB2, RAD51B, RAD51C or RAD51D.
Participants with evaluable disease must have documented radiological progressive cancer before study entry.
For prostate cancer, PSA progression per PCWG3 is acceptable (Part 1)
ECOG Performance Status of 0 to 1
Life expectancy must be ≥ 12 weeks
Have adequate organ function
Female Participants should meet ≥ 1 of the following criteria: a. Lack of childbearing potential b. Post-menopausal c. For those with childbearing potential, have a negative pregnancy test at screening, not be in lactation, and willing to take highly effective contraceptive
Male participants had a vasectomy or use highly effective methods of (from day-0 to 6 months after last dose of IMP)
For PARPi-treated participants, up to 1 prior nonselective PARPi-containing treatment (treatment or maintenance) is allowed (Part 1 only).
CNS Inclusion (Backfill Cohort): Participants must have one of the following:
Untreated CNS Metastases.
Previously treated CNS Metastases: a. Screening MRI must show no lesion increase >10 mm in 4 weeks b. Participants with new CNS lesions treated during Screening may enroll if: • WBRT >28 days, SRS >14 days, or surgery >28 days before first treatment dose. • Non-CNS sites of evaluable disease are present.

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Exclusion Criteria

Any participants treated with anti-cancer therapies
Participants that received prior PARP1-selective inhibitors
Participants who have undergone: major surgery, extensive field radiotherapy, palliative radiotherapy OR used a radioactive drug
Participants with other malignancies requiring treatment within 2 years before 1st dose of IMP
Participants previous treatment-related toxicities that have not recovered, i.e., to ≤ Grade 1, as evaluated by NCI-CTCAE or baseline (Grade 2 and other non clinically significant toxicities can be enrolled)
Participants with any of the following cardiac criteria: a. mean resting QTcF > 470 ms b. any factors that increase the risk of QT prolongation, or use of concomitant drugs that may prolong/shorten QT and at risk of Torsades de Pointes; c. any clinically important abnormalities of resting ECG
Participants with other cardiovascular diseases as defined by any of the following: a. symptomatic heart failure b. uncontrolled hypertension c. hypertensive heart disease d. acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure e. cardiomyopathy f. presence of clinically significant valvular heart disease g. history of arrhythmia requiring treatment; Participants with atrial fibrillation and optimally controlled ventricular rate are permitted h. transient ischemic attack or stroke within 6 months prior to Screening i.participants with symptomatic hypotension at Screening
Participants with infections, including: a. An uncontrolled acute infection, an active infection requiring systemic treatment, prophylactic use of systemic antibiotics is allowed b. HIV-infected participants must have well-controlled HIV and be on ART defined as: i. must have a CD4+ T-cell count ≥ 350 cells/mm3 at screening, ii. must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 copies/mL or the LLOQ iii. must not have had any AIDS-defining opportunistic infections within the past 12 months, iv. must have been on a stable regimen for at least 4 weeks before study entry and agree to continue ART throughout the study, v. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates c. A known active Hep B/C infection d. Active tuberculosis
Any major illness that will substantially increase the risk associated with the patient’s participation in this study
Participants with a diagnosis of MDS or AML or have received transplantation.
11.Participants with any known predisposition to bleeding.
Live/attenuated vaccine within 28 days prior to the 1st dose of IMP
COVID-19 vaccine within 72 hours prior to 1st dose of IMP
Participants with administration of any strong inhibitors/inducers of CYP3A4 or P-gp inhibitors within 28 days or 5 half-lives (whichever is shorter) prior to the 1st dose of the IMP
Participants who may need continuous treatment with PPIs or P-CABs or H2-blockers during the study period
Participants with a known history of hypersensitivity to the study drug or any of its excipients.
Participants who are unable to swallow oral medications,
Female participants who are pregnant or lactating/breastfeeding.
Participants known to have a history of alcoholism or drug abuse
Participants who have participated in another clinical study with an investigational product administered in the last 28 days
21.Have used an investigational device within 28 days prior to the first dose of study drug.
22.Participants with active or untreated CNS metastases and/or carcinomatous meningitis based on Screening brain MRI (Pt1 & 2)
CNS Exclusion (Backfill):
Any untreated brain lesions > 2.0 cm in size.
Ongoing use of systemic corticosteroids to control symptoms of CNS metastases.
Any Brain lesion requiring immediate local therapy
26.Known symptomatic leptomeningeal disease.
Have poorly controlled seizures.