A first-in-human study of PARP1 selective inhibitor, IMP1734, in patients with advanced solid tumors.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eikon Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Nov 2024 → ongoing

Decision date (initial)

2024-07-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Eikon Therapeutics, Inc.

External identifiers

EU CT number

2023-509230-19-00

ClinicalTrials.gov

NCT06253130

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Efficacy, Dose response, Pharmacogenetic, Therapy, Pharmacokinetic

Part 1 and 2:
To evaluate the safety and tolerability of EIK1003 as monotherapy and in combination with anti-cancer agents
To evaluate the safety and tolerability of EIK1003 and to determine the optimal dose (Part 2)

Secondary objectives 1

1. To characterize the plasma PK profile of single and multiple doses of EIK1003 (Part 1 and Part 2) To assess preliminary anti-tumor activity of EIK1003 as monotherapy and in combination with anti-cancer agents (Part 1) To evaluate the efficacy of EIK1003 and to determine the optimal dose (Part 2)

Conditions and MedDRA coding

Advance solid tumors

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants must voluntarily participate and comply with study procedures
2. 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
3. Male participants had a vasectomy or use highly effective methods of (from day-0 to 6 months after last dose of IMP)
4. 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)
5. Participants with EOC, fallopian tube, or primary peritoneal cancer should be platinum sensitive (Pt3 only)
6. 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)
7. No prior therapy with a PARPi (Pt3 Cohort 3A only)
8. Received 1 and only 1 prior PARPi (Pt3 Cohort 3B only)
9. Participants must be ≥ 18 years of age
10. 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)
11. Participants are required to have deleterious or suspected deleterious germline or somatic mutations (Cohort-1A/1B and Pt3)
12. 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

Exclusion criteria 25

1. Any participants treated with anti-cancer therapies
2. Participants that received prior PARP1-selective inhibitors
3. Participants who have undergone: major surgery, extensive field radiotherapy, palliative radiotherapy OR used a radioactive drug
4. Participants with other malignancies requiring treatment within 2 years before 1st dose of IMP
5. 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)
6. Participants with active CNS metastases and/or carcinomatous meningitis.
7. 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
8. 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
9. 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
10. Any major illness that will substantially increase the risk associated with the patient’s participation in this study
11. Participants with a diagnosis of MDS or AML or have received transplantation
12. Participants with any known predisposition to bleeding
13. Live/attenuated vaccine within 28 days prior to the 1st dose of IMP
14. COVID-19 vaccine within 72 hours prior to 1st dose of IMP
15. 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
16. Participants who may need continuous treatment with PPIs or P-CABs or H2-blockers during the study period
17. Receiving continuous prednisone or equivalent
18. Participants with a known history of hypersensitivity to the IMP or its ingredients.
19. Participants unable to swallow oral medications OR have malabsorption syndrome/uncontrolled GI condition
20. Female Participants who are pregnant or lactating/breastfeeding
21. Participants with a known history of alcoholism/drug abuse
22. Participants who have participated in another clinical study with an IMP administered in the last 28 days or five half-lives (whichever is shorter)
23. Have used an investigational device within 28 days prior to the first dose of IMP
24. Cohort 1B only (mCSPC): Must not received prior treatment with 2nd generation or investigational AR, or CYP17 enzyme inhibitors
25. Cohort 1C only: Participants with ≥ Grade 2 peripheral neuropathy at time of screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Part 1 and 2: • TEAEs • DLTs • Laboratory parameters • Vital signs • ECGs

Secondary endpoints 5

1. 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
2. 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
3. • 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).
4. • 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
5. • PFS • OS • For prostate cancer only: o PSA response per PCWG3 criteria o PSA progression o PSA complete response rate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eikon Therapeutics Inc.

Sponsor organisation

Eikon Therapeutics Inc.

Address

450 East 29th Street Floor 15th

City

New York

Postcode

10016-8367

Country

United States

Scientific contact point

Organisation

Eikon Therapeutics Inc.

Contact name

Viola Chen

Public contact point

Organisation

Eikon Therapeutics Inc.

Contact name

Leah Gilbert

Third parties 12

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications