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, EIK1003 (IMP1734), as monotherapy and in combination in participants with advanced solid tumors.
Date de révision : 28/04/2026
15 participants
Homme Femme
A partir de 18 ans
Date de début de recrutement : 27/07/2025
Critères :
Critères d'inclusion :
- Participants must voluntarily participate and comply with study procedures
- 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)
- Both PARPi-treated and PARPi-naïve participants are eligible. For PARPi-treated participants, up to 1 prior PARPi containing treatment is allowed (Pt 1 only)
- Participants with EOC, fallopian tube, or primary peritoneal cancer must have received 1 and only 1 prior PARPi containing treatment (Pt2 only)
- Participants with EOC, fallopian tube, or primary peritoneal cancer should be platinum sensitive (Pt3 only)
- Breast cancer participants are eligible provided no evidence of progression. Participants who previously received platinum-based chemotherapy as neo-adjuvant/adjuvant are eligible provided at least 12 months, between this treatment, and 1st dose of IMP (Pt3 only)
- No prior therapy with a PARPi (Pt3 Cohort 3A only)
- Received 1 and only 1 prior PARPi (Pt3 Cohort 3B only)
- 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. Must be platinum resistant (Cohort-1C only) iii. 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 (Cohort-1A/C and Pt3): 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 mPC (Cohort-1A/1B and Pt3): i. mCRPC: With ongoing ADT within 28 days before study start. Participants receiving ADT should continue treatment during the study ii. mCSPC (Cohort-1B only) Candidates for ADT and/or started ADT but no longer than 12 weeks before study start or with bilateral orchiectomy iii. Prior therapies: a. Must have received a novel hormonal agent (Cohort-1A and Pt3:mCRPC) b. Must have received up to 1 prior taxane based chemotherapy/ineligible for chemotherapy (Cohort1A, Pt3; mCRPC) c. May have received up to one prior therapy with an NHA and/or PARPi or taxane treatment (Cohort1B; mCRPC) iv. Should have evaluable disease defined as (Cohort1A/1B and Pt3): 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 d) Histologically/cytologically confirmed advanced/recurrent/ mPDAC (Cohort-1A) 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 (Cohort-1A/1B and Pt3)
- Participants with RECIST v1.1-evaluable disease must have documented radiological progressive cancer before study entry. Prostate cancer participants whose is limited to regional pelvic lymph nodes/local recurrence, not eligible
- For prostate cancer, PSA progression per PCWG3 is acceptable (Cohort-1A/1B and Pt3)
- ECOG Performance Status of 0 to 1
- Life expectancy must be ≥ 12 weeks
- Have adequate organ function
Critères d'exclusion :
- Any participants treated with anti-cancer therapies
- 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
- 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
- Receiving continuous prednisone or equivalent
- Participants with a known history of hypersensitivity to the IMP or its ingredients.
- Participants unable to swallow oral medications OR have malabsorption syndrome/uncontrolled GI condition
- Participants that received prior PARP1-selective inhibitors
- Female Participants who are pregnant or lactating/breastfeeding
- Participants with known history of alcoholism/drug abuse
- Participants who have participated in another clinical study with an IMP administered in the last 28 days or five half-lives (whichever is shorter)
- Have used an investigational device within 28 days prior to the first dose of IMP
- Cohort 1B only (mCSPC): Must not received prior treatment with 2nd generation or investigational AR, or CYP17 enzyme inhibitors
- Cohort 1C only: Participants with ≥ Grade 2 peripheral neuropathy at time of screening
- 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 active CNS metastases and/or carcinomatous meningitis.
- Participants with any of the following cardiac criteria: a. mean resting QTcF > 470 ms or QTcF < 340 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. 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
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Pour participer à cet essai clinique, veuillez contacter la personne responsable de l'étude. Vous trouverez ses coordonnées dans la section "Lieux et contacts", puis "Contacts".