A study to investigate WEF-001 in patients with Advanced KRAS-Mutant Solid Tumours.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Auricula Biosciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-08-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Auricula Biosciences Inc., United States of America

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others

Primary Objective: Phase 1
1. To characterize the safety and tolerability profiles of WEF-001 administered as monotherapy.
2. To establish the MTD and RP2Ds.

Primary Objective: Phase 2a
1. To evaluate the antitumour activity following WEF-001 administration as monotherapy.

Secondary objectives 2

1. Secondary Objectives - Phase 1: 1. To characterize the PK of WEF-001, as well as total and free MMAE following WEF-001 administration as monotherapy. 2. To evaluate the preliminary evidence of anti-tumour activity following WEF-001 administration as monotherapy.
2. Secondary Objectives - Phase 2a: 1. To evaluate other response-related outcomes to assess anti-tumour activity following WEF-001 administration as monotherapy. 2. To characterize the safety and tolerability profile of WEF-001 administered as monotherapy to participants. 3. To characterize the PK of WEF-001, as well as total and free MMAE following WEF-001 administration as monotherapy.

Conditions and MedDRA coding

Advanced KRAS- Mutant Solid Tumours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Participant must be 18 years old or older, at the time of signing the informed consent.
2. 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.
3. 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.
4. 4. Measurable disease as defined by RECIST v1.1 (Section 10.6).
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status <1 (Section 10.5).
6. 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.
7. 7. Have adequate venous access to allow for blood sampling and IV doses.
8. 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 12

1. 1. Any active systemic infection requiring anti-infective therapy within 28 days prior to first dose of IMP.
2. 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
3. 3. Have a second active primary malignancy, requiring systemic administration of any cancer-related therapy, with the exception of luteinizing hormone-releasing hormone analogs.
4. 4. Have a clinical diagnosis of child-Pugh B or C liver disease.
5. 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.
6. 6. Have a diagnosis of inflammatory bowel disease.
7. 7. Have active and untreated hyperthyroidism.
8. 8. Have a history (within the past 5 years) of, or presence of, systemic lupus erythematosus.
9. 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.
10. 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.
11. 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.
12. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. Primary Endpoints - Phase 2a: 1. ORR according to RECIST v 1.1.

Secondary endpoints 2

1. 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.
2. 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.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Auricula Biosciences Inc.

Sponsor organisation

Auricula Biosciences Inc.

Address

200 Continental Drive Suite 401

City

Newark

Postcode

19713-4337

Country

United States

Scientific contact point

Organisation

Auricula Biosciences Inc.

Contact name

Cynthia Cardinal

Public contact point

Organisation

Auricula Biosciences Inc.

Contact name

Cynthia Cardinal

Third parties 6

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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