WEF-001 for Advanced KRAS‑mutant solid tumours

Inclusion criteria

• {"criterion_text":"- 1. Participant must be 18 years old or older, at the time of signing the informed consent.\n- 2. Have a histologically or cytologically confirmed advanced or metastatic KRAS-mutant tumour. a) Phase 1: KRAS-mutant solid tumours – (PDAC, CRC, NSCLC, platinumresistant serous ovarian cancer, cholangiocarcinoma, or urothelial bladder cancer). b) Phase 2a: One KRAS-mutant solid tumour type to be selected from PDAC, CRC, or NSCLC. Note: See SoA (Section 1.3) for more information on the biopsy sampling.\n- 3. Progressive disease following at least one line of standard of care therapy: a) Patients with Microsatellite instability-high (MSI-H)/ deficient DNA mismatch repair (dMMR) metastatic CRC (mCRC) must have received at least one prior line of therapy with a PD-1 inhibitor. b) Patients with genomic alterations or other biomarkers for which there is approved target therapy for their specific tumor type should have received such therapy.\n- 4. Measurable disease as defined by RECIST v1.1 (Section 10.6).\n- 5. Eastern Cooperative Oncology Group (ECOG) performance status <1 (Section 10.5).\n- 6. Recovered from clinically significant toxicities of prior therapies to Grade ≤1 or baseline, except for alopecia. Participants with ongoing endocrinopathies due to prior treatment that have not resolved but are on appropriate replacement therapy (e.g., thyroid, adrenal or pituitary) are permitted to enroll.\n- 7. Have adequate venous access to allow for blood sampling and IV doses.\n- 8. Adequate organ function, demonstrated by the following laboratory values (Table 5.1). a) If a participant is receiving anticoagulant therapy, an international normalized ratio (INR) >1.5 would be acceptable, if within the expected therapeutic range for the concomitant medication being used, and after discussion with the medical monitor prior to enrollment."}

Exclusion criteria

• {"criterion_text":"- 1. Any active systemic infection requiring anti-infective therapy within 28 days prior to first dose of IMP.\n- 10. Prior/Concurrent Clinical Study Experience: Are currently enrolled in, or discontinued within 30 days prior to first dose from, a clinical trial involving an investigational product, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.\n- 11. Are pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 180 days after the last dose of study medication. Participants who have stopped breastfeeding may be enrolled.\n- 12. Currently employed at Auricula Biosciences, or study-associated Contract Research Organization employees; investigator or site personnel directly affiliated with this study and their immediate families.\n- 2. Have an active cardiovascular disease, including: a. Unstable angina b. Myocardial infarction within 6 months prior to study drug administration c. New York Heart Association (NYHA) Class III or IV heart failure d. Electrocardiogram (ECG) abnormality that, in the opinion of the investigator, increases the risks associated with participating in the study e. Electrocardiogram (ECG) abnormality: QTc (Fredericia) >470ms\n- 3. Have a second active primary malignancy, requiring systemic administration of any cancer-related therapy, with the exception of luteinizing hormone-releasing hormone analogs.\n- 4. Have a clinical diagnosis of child-Pugh B or C liver disease.\n- 5. Participants with untreated brain metastases and/or who are neurologically unstable and/or who are not receiving a stable or decreasing corticosteroid dose may not be included in the study.\n- 6. Have a diagnosis of inflammatory bowel disease.\n- 7. Have active and untreated hyperthyroidism.\n- 8. Have a history (within the past 5 years) of, or presence of, systemic lupus erythematosus.\n- 9. Have any other concurrent severe and/or uncontrolled medical or surgical condition which, in the view of the investigator, could compromise the participant’s involvement in the trial due to safety, compliance concerns or ability to evaluate response."}

Primary endpoints

• {"endpoint_text":"- Primary Endpoints - Phase 1: 1. Type, incidence and severity of TEAEs, SAEs and abnormal laboratory values per CTCAE v5.0. 2. Frequency of dose interruptions, reductions, and discontinuations. 3. Proportion of participants with DLTs at each dose level.\n- Primary Endpoints - Phase 2a: 1. ORR according to RECIST v 1.1.","definition_or_measurement_approach":"Phase 1 endpoints: Safety and tolerability measured as type/incidence/severity of TEAEs and SAEs and laboratory abnormalities per CTCAE v5.0; frequency of dose interruptions/reductions/discontinuations; proportion of participants with dose-limiting toxicities (DLTs) at each dose level. Phase 2a endpoint: Objective response rate (ORR) assessed according to RECIST v1.1."}

Secondary endpoints

• {"endpoint_text":"- Secondary Endpoints - Phase 1: 1. PK parameters including, but not limited to a. AUC, b. Cmax, c. Tmax, d. T1/2 e. Clearance, f. Vd. 2. BOR, with calculation of ORR as a sum of CR or PR, and DCR as a sum of CR, PR, or SD, PFS, TTR and DOR according to RECIST v 1.1.\n- Secondary Endpoints - Phase 2a: 1. DCR, DOR, and PFS according to RECIST v 1.1. 2. Type, incidence and severity of TEAEs, SAEs and clinical laboratory abnormalities per CTCAE v5.0. 3. Frequency of dose interruptions, reductions, and discontinuations. 4. PK parameters including, but not limited to a. AUC, b. Cmax, c. Tmax, d. T1/2, e. Clearance, f. Vd.","definition_or_measurement_approach":"Phase 1: Pharmacokinetic parameters (AUC, Cmax, Tmax, T1/2, clearance, Vd) and best overall response (BOR) with ORR (CR+PR), disease control rate (DCR = CR+PR+SD), progression-free survival (PFS), time to response (TTR), and duration of response (DOR) per RECIST v1.1. Phase 2a: DCR, DOR, PFS per RECIST v1.1; safety and laboratory abnormalities per CTCAE v5.0; dose interruption/reduction/discontinuation frequency; PK parameters as listed."}

Spain

Earliest CTIS Part Ii Submission Date

02-07-2025

Latest Decision Or Authorization Date

04-08-2025

Processing Time Days

33

Number Of Sites

2

Number Of Participants

27

Primary sponsor

Full Name

Auricula Biosciences Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States of America

Contract research organisations

Name

Simbec Research Limited

Responsibilities

ClinHUB – Data Collation and Aggregation Hub – Ingest, Aggregate, Standardize and Integrate data from Veeva CTMS and Oracle InForm; BI Tool – Analytic (duties contracted to Thoughtsphere).

Third parties

• {"country":"United Kingdom","full_name":"Simbec Research Limited","duties_or_roles":"ClinHUB – Data Collation and Aggregation Hub – Ingest, Aggregate, Standardize and Integrate data from Veeva CTMS and Oracle InForm; - BI Tool – Analytic. Duties contracted to Thoughtsphere.","organisation_type":"Pharmaceutical company"}
• {"country":"United States of America","full_name":"Eurofins Lancaster Laboratories LLC","duties_or_roles":"Central Analysis of PK, PD, and ctDNA Biomarker samples; Archival of Plasma and stool sample biomarkers for potential future analysis.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Oracle France","duties_or_roles":"InForm eCRF (EDC) and RTSM.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Sharp Clinical Services (UK) Limited","duties_or_roles":"Labelling, Packing, Depot/Storage, and Distribution services of Study IMP.","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Canopy Life Sciences Limited","duties_or_roles":"eCTD Publishing and submissions in accordance with Regulatory guidelines (ICH and Regional) per FDA requirements and other documents as required.","organisation_type":"Pharmaceutical company"}
• {"country":"United States of America","full_name":"Veeva Systems Inc.","duties_or_roles":"eTMF / CTMS Provider.","organisation_type":"Non-Pharmaceutical company"}