ETX-19477 for Advanced solid malignancies | Ovarian epithelial cancer | Castration-resistant prostate cancer | Breast cancer

Inclusion criteria

• {"criterion_text":"- 1.) Males and females of age ≥18 years at the time of signing the informed consent document.\n- 10.) All toxicity resulting from prior cancer therapies must have resolved to NCI CTCAE v5.0 Grade ≤1 or pre-therapy baseline with the exception of alopecia or ≤ Grade 2 neuropathy (except for laboratory parameters outlined below).\n- 11.)\tAdequate hematological, renal, and hepatic function: a)\tANC ≥1.5×109/L (no GCSF within 14 days of study enrollment) b)\tPlatelet count ≥ 100×109/L (no platelet transfusions within 7 days of study enrollment) c)\tHemoglobin ≥10.0 g/dL (no RBC transfusions within 14 days of study enrollment) d)\tAlbumin >3.0 g/dL e)\tALT ≤3×ULN (if liver metastases are present, ≤5.0×ULN) f)\tAST ≤3×ULN (if liver metastases are present, ≤5.0×ULN) g)\tTotal bilirubin ≤1.5×ULN (patients with known Gilbert’s Syndrome may enroll with 2.5×ULN provided the direct bilirubin is ≤1.5 mg/dL) h)\tCalculated estimated glomerular filtration rate of ≥50 mL/minute/1.73m2 by CKD-EPI equation (see Section 14.11) i)\tPT and/or INR and PTT or aPTT ≤1.5×ULN\n- 12.) No investigational agent within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug\n- 13.) Female patients of childbearing potential must agree to use highly effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment. Male patients must be surgically sterile or abstinent or both the male and their female partners of childbearing potential must agree to use highly effective contraception with supplementary barrier method (male condom) during the period of therapy and in the following 90 days after discontinuation of study treatment.\n- 14.) Able to swallow an oral medication.\n- 15.) Willing and able to adhere to the study visit schedule and other protocol requirements.\n- 2.) Able to understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.\n- 3.) Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary CNS tumors.\n- 4.) Progression on or after or intolerance to most recent systemic therapy. Prior treatment in the recurrent/metastatic setting; patients must have received approved standard therapy that is available to the patient that is known to confer clinical benefit, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient. The reason for treatment decline must be clearly documented in the medical record and Sponsor Medical Monitor approval obtained.\n- 5.) The following tumor profiles are eligible: a)\tPhase 1: Any solid tumor malignancy, excluding primary CNS tumors, with progression on or after or intolerance to most recent systemic therapy. b)\tPhase 2: i)\tEpithelial ovarian cancer: No more than 4 prior regimens for locally advanced/metastatic disease including at least 1 line of platinum-based chemotherapy. ii)\tER+ Breast cancer: No more than 4 prior regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies). iii)\tCastration-Resistant Prostate Cancer: No more than 4 prior regimens. Previous taxane chemotherapy is allowed. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or orchiectomy (ie, surgical or medical castration) is mandatory. Serum testosterone levels of ≤50 ng/dL (≤1.75 nmol/L) within (≤) 28 days prior to first dose of study drug. iv)\tAdvanced non-breast, non-ovarian, and non-prostate tumor types: No more than 4 prior regimens.\n- 6.) Measurable disease per RECIST v1.1. Additionally, patients with breast, prostate, or ovarian cancer with non-measurable, evaluable disease are eligible.\n- 7.) ECOG performance status 0–1.\n- 8.) Life expectancy of at least 3 months.\n- 9.) Willing to provide a pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy [preferably from a progressing lesion and preferably obtained during or after disease progression on last regimen received]). Patients without available archival tissue and/or where biopsy is not considered safe and/or medically feasible may be enrolled with approval of the Sponsor Medical Monitor."}

Exclusion criteria

• {"criterion_text":"- 1.)  Receiving continuous corticosteroids at prednisone-equivalent dose of >10 mg/day. Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg/day of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted.\n- 10.) Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert’s Syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per Investigator assessment).\n- 11.) Known other previous/current malignancy requiring treatment within ≤2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma.\n- 12.) Pregnant or breastfeeding. Patients with elevated human chorionic gonadotropin due to underlying malignancy may be eligible if confirmed not to be pregnant.\n- 13.) Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants\n- 14.) Any other prior or ongoing significant medical condition, physical finding, laboratory abnormality, psychiatric illness, or social situation that, in the opinion of the Investigator or Medical Monitor, could impact safety or compliance with study requirements or confounds the ability to interpret data.\n- 2.) Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug. If previously irradiated, lesions must have demonstrated clear-cut progression prior to being eligible for evaluation as target lesions.\n- 3.) Major surgery (excluding placement of vascular access) ≤28 days of the first dose of study drug.\n- 4.) Symptomatic untreated or progressing brain metastases. Stable, treated brain metastases are allowed if no evidence of radiologic or clinical progression or corticosteroid use for at least 4 weeks.\n- 5.) Impairment of GI function or GI disease that may significantly alter the absorption of ETX 19477 and no history of bowel obstruction within 6 months prior to enrollment.\n- 6.) Known symptomatic and radiologically progressing or LMD. If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator, the patient must be free of neurological symptoms of LMD.\n- 7.) Resting ECG with QTcF >470 msec on 2 or more timepoints within a 24-hour period, or history or family history of congenital long QT syndrome.\n- 8.) History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, clinically significant uncontrolled arrhythmias, or any history of symptomatic congestive heart failure.\n- 9.) Known active or chronic infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B, hepatitis C, or AIDS-related illness. Controlled infections, including HIV and “cured” hepatitis C (no active fever, no evidence of systemic inflammatory response syndrome) that are stable with undetectable viral load on antiviral treatment are not exclusionary."}

Primary endpoints

• {"endpoint_text":"- Phase 1: - Frequency of dose-limiting toxicities (DLTs) - Frequency and severity of AEs, including abnormal ECG parameters, and serious adverse events (SAEs)\n- Phase 2: Objective response rate","definition_or_measurement_approach":"Phase 1: Frequency of DLTs and frequency/severity of AEs and SAEs as reported by the study (AEs likely graded using NCI CTCAE v5.0 per protocol references). DLTs defined per protocol. Phase 2: Objective response rate measured by RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: -Plasma concentrations of ETX-19477 as a function of time post-dosing -PK parameters for single (first) dose and multiple doses\n- Phase 1: \t - Objective response rate (ORR) - Duration of response (DOR) - Disease control rate (DCR) - Progression-free survival (PFS)\n- Phase 2: - Frequency and severity of AEs and SAEs.\n- Phase 2: - Duration of response (DOR) - Disease control rate (DCR) - Progression-free survival (PFS)","definition_or_measurement_approach":"PK endpoints: plasma concentrations over time and standard PK parameters for single and multiple doses. Tumor response endpoints (ORR, DOR, DCR, PFS) measured using RECIST v1.1 and conventional time-to-event analyses. AEs/SAEs assessed and reported per study safety procedures (AEs likely graded per NCI CTCAE v5.0)."}

France

Earliest CTIS Part Ii Submission Date

18-02-2025

Latest Decision Or Authorization Date

02-04-2025

Processing Time Days

43

Number Of Sites

4

Number Of Participants

10

Italy

Earliest CTIS Part Ii Submission Date

04-03-2025

Latest Decision Or Authorization Date

01-04-2025

Processing Time Days

28

Number Of Sites

4

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

17-03-2025

Latest Decision Or Authorization Date

31-03-2025

Processing Time Days

14

Number Of Sites

5

Number Of Participants

12

Primary sponsor

Full Name

858 Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Contract Negotiations, Investigator Site Payments, Trial Master File maintenance (and multiple sponsor duties codes listed in sponsor record)

Third parties

• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"sponsorDuties codes: [1,10,12,13,14,15,2,3,5,6,7,8,9]; duties (text): Contract Negotiations, Investigator Site Payments, Trial Master File maintenance","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}