EIK1003 for Advanced solid tumors

Inclusion criteria

• {"criterion_text":"- Participants must voluntarily participate and comply with study procedures"}
• {"criterion_text":"- Participants must have 1 of the following: a. Confirmed advanced/recurrent/metastatic, endometrioid EOC, fallopian tube or primary peritoneal cancer (Cohorts-1A and 1C, 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 Pt2): i. Must have received ≥ 1 prior chemotherapy (Part 2 only) ii Must be PARPi-naïve (Part 2 only) iii. Participants with HR+ must have received hormonal therapy iv. Should have evaluable disease defined as ≥ 1 measurable lesion c. Confirmed adenocarcinoma mPC (Cohort-1A/1B): 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:mCRPC) b. Must have received up to 1 prior taxane based chemotherapy/ineligible for chemotherapy (Cohort1A, 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): 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 4. Participants are required to have deleterious or suspected deleterious germline or somatic mutations (Cohort-1A and Pt2) a. Participants with mPC must have deleterious/suspected deleterious germline or somatic mutations (Cohort-1B) 5. 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 6. For prostate cancer, PSA progression per PCWG3 is acceptable (Cohort-1A/1B) 7. ECOG Performance Status of 0 to 1 8. Life expectancy must be ≥ 12 weeks 9. Have adequate organ function 10. 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 11. Male participants had a vasectomy or use highly effective methods of (from day-0 to 6 months after last dose of IMP) 12. 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)"}
• {"criterion_text":"- Participants are required to have deleterious or suspected deleterious germline or somatic mutations (Cohort-1A/1B and Pt3)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Male participants had a vasectomy or use highly effective methods of (from day-0 to 6 months after last dose of IMP)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Participants with EOC, fallopian tube, or primary peritoneal cancer should be platinum sensitive (Pt3 only)"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- No prior therapy with a PARPi (Pt3 Cohort 3A only)"}
• {"criterion_text":"- Received 1 and only 1 prior PARPi (Pt3 Cohort 3B only)"}
• {"criterion_text":"- Participants must be ≥ 18 years of age"}

Exclusion criteria

• {"criterion_text":"- Any participants treated with anti-cancer therapies"}
• {"criterion_text":"- Any major illness that will substantially increase the risk associated with the patient’s participation in this study"}
• {"criterion_text":"- Participants with a diagnosis of MDS or AML or have received transplantation"}
• {"criterion_text":"- Participants with any known predisposition to bleeding"}
• {"criterion_text":"- Live/attenuated vaccine within 28 days prior to the 1st dose of IMP"}
• {"criterion_text":"- COVID-19 vaccine within 72 hours prior to 1st dose of IMP"}
• {"criterion_text":"- Participants with administration of any strong and moderate 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"}
• {"criterion_text":"- Participants who may need continuous treatment with PPIs or P-CABs or H2-blockers during the study period"}
• {"criterion_text":"- Receiving continuous prednisone or equivalent"}
• {"criterion_text":"- Participants with a known history of hypersensitivity to the IMP or its ingredients."}
• {"criterion_text":"- Participants unable to swallow oral medications OR have malabsorption syndrome/uncontrolled GI condition"}
• {"criterion_text":"- Participants that received prior PARP1-selective inhibitors"}
• {"criterion_text":"- Female Participants who are pregnant or lactating/breastfeeding"}
• {"criterion_text":"- Participants with a known history of alcoholism/drug abuse"}
• {"criterion_text":"- Participants who have participated in another clinical study with an IMP administered in the last 28 days or five half-lives (whichever is shorter)"}
• {"criterion_text":"- Have used an investigational device within 28 days prior to the first dose of IMP"}
• {"criterion_text":"- Cohort 1B only (mCSPC): Must not received prior treatment with 2nd generation or investigational AR, or CYP17 enzyme inhibitors"}
• {"criterion_text":"- Cohort 1C only: Participants with ≥ Grade 2 peripheral neuropathy at time of screening"}
• {"criterion_text":"- Participants who have undergone: major surgery, extensive field radiotherapy, palliative radiotherapy OR used a radioactive drug"}
• {"criterion_text":"- Participants with other malignancies requiring treatment within 2 years before 1st dose of IMP"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Participants with active CNS metastases and/or carcinomatous meningitis."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- Part 1 and 2: • TEAEs • DLTs • Laboratory parameters • Vital signs • ECGs","definition_or_measurement_approach":"Safety and tolerability assessments including treatment-emergent adverse events (TEAEs), dose-limiting toxicities (DLTs), laboratory parameters, vital signs and ECGs assessed in Parts 1 and 2."}

Secondary endpoints

• {"endpoint_text":"- PK parameters derived from plasma concentration data of EIK1003 and/or metabolites (if applicable) following single oral dose: • Cmax, Tmax, AUC0-t, AUC0-tau, Cmax(dn), and AUC0-tau(dn) • If data permit, AUC0-inf, CL/F, Vd/F, and t1/2","definition_or_measurement_approach":"Pharmacokinetic parameters measured from plasma concentration data after single oral dose (Cmax, Tmax, AUC measures; if data permit, AUC0-inf, CL/F, Vd/F, t1/2)."}
• {"endpoint_text":"- PK parameters derived from plasma concentration data of EIK1003 and/ormetabolites (if applicable) following multiple oral doses: • Cmax,ss, Ctrough, Tmax,ss, AUC0-t,ss, AUC0-tau,ss, Cmax,ss(dn), AUC0-tau(dn), Rac-Cmax,ss and Rac-AUC0-tau,ss","definition_or_measurement_approach":"Steady-state pharmacokinetic parameters measured from plasma after multiple oral doses (Cmax,ss, Ctrough, Tmax,ss, AUC0-t,ss, AUC0-tau,ss, accumulation ratios)."}
• {"endpoint_text":"- • If data permit, CL/F, Vd/F, and t1/2 • Overall response rate, which is defined as the percentage of participants who have CR/PR per RECIST v1.1, by Investigator and/or CA125 response per GCIG criteria (ovarian cancer), and/or PSA and/or bone scan response per PCWG3 criteria (prostate cancer).","definition_or_measurement_approach":"Pharmacokinetic parameters where available (CL/F, Vd/F, t1/2) and overall response rate assessed by Investigator per RECIST v1.1 and disease-specific criteria (GCIG CA125 for ovarian cancer; PCWG3 PSA/bone scan for prostate cancer)."}
• {"endpoint_text":"- • Efficacy evaluated per RECIST v1.1 by Investigator: o ORR o DCR o DOR o TTR o Percentage change in sum of target lesions o CBR, which is defined as the proportion of participants with BOR of CR, PR or lasting ≥ 18 weeks of SD after the start of the study drug • PFS • OS • For prostate cancer only: o PSA response per PCWG3 criteria o PSA progression o PSA complete response rate","definition_or_measurement_approach":"Investigator-assessed efficacy per RECIST v1.1 (ORR, disease control rate, duration of response, time to response, change in target lesions, clinical benefit rate) and survival endpoints (PFS, OS). Prostate-cancer-specific PSA endpoints per PCWG3."}
• {"endpoint_text":"- • PFS • OS • For prostate cancer only: o PSA response per PCWG3 criteria o PSA progression o PSA complete response rate","definition_or_measurement_approach":"Progression-free survival (PFS) and overall survival (OS); prostate cancer specific PSA response/progression and complete response per PCWG3."}

France

Earliest CTIS Part Ii Submission Date

01-07-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

667

Number Of Sites

3

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

20-05-2024

Latest Decision Or Authorization Date

04-05-2026

Processing Time Days

714

Number Of Sites

12

Number Of Participants

60

Denmark

Earliest CTIS Part Ii Submission Date

16-07-2024

Latest Decision Or Authorization Date

30-04-2026

Processing Time Days

654

Number Of Sites

1

Number Of Participants

12

Primary sponsor

Full Name

Eikon Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

sponsorDuties codes: [{"id":917719,"code":"4"}]

Name

Pharmaceutical Research Associates Group B.V.

Responsibilities

sponsorDuties codes: [{"id":917706,"code":"4"}]

Name

Novotech

Responsibilities

sponsorDuties codes: [{"id":917717,"code":"4"}]

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties: [{"id":917709,"code":"12"}, {"id":917710,"code":"15","value":"Kit production and sample storage"}, {"id":917711,"code":"4"}, {"id":917712,"code":"5"}]

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"sponsorDuties codes: [ {\"id\":917719,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Kayentis","duties_or_roles":"sponsorDuties codes: [ {\"id\":917714,\"code\":\"7\"} ]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"sponsorDuties codes: [ {\"id\":917706,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties: [ {\"id\":917718,\"code\":\"15\",\"value\":\"QP site\"} ]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"sponsorDuties: [ {\"id\":917707,\"code\":\"15\",\"value\":\"Clinical site payments\"} ]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"sponsorDuties codes: [ {\"id\":917713,\"code\":\"4\"} ]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Scisafe Inc.","duties_or_roles":"sponsorDuties: [ {\"id\":917705,\"code\":\"15\",\"value\":\"Sample storage\"} ]","organisation_type":"Pharmaceutical company"}
• {"country":"Taiwan","full_name":"Novotech","duties_or_roles":"sponsorDuties codes: [ {\"id\":917717,\"code\":\"4\"} ]","organisation_type":"Health care"}
• {"country":"Spain","full_name":"Atrys Health S.A.","duties_or_roles":"sponsorDuties codes: [ {\"id\":917716,\"code\":\"4\"} ]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Natera Inc.","duties_or_roles":"sponsorDuties codes: [ {\"id\":917715,\"code\":\"4\"} ]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties: [ {\"id\":917708,\"code\":\"15\",\"value\":\"Patient reimbursement\"} ]","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties: [ {\"id\":917709,\"code\":\"12\"}, {\"id\":917710,\"code\":\"15\",\"value\":\"Kit production and sample storage\"}, {\"id\":917711,\"code\":\"4\"}, {\"id\":917712,\"code\":\"5\"} ]","organisation_type":"Pharmaceutical company"}