Study of Zelenectide Pevedotin in Participants with Advanced Breast Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bicycletx Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Jun 2025 → ongoing

Decision date (initial)

2025-06-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BicycleTx Limited

External identifiers

EU CT number

2024-517868-33-00

WHO UTN

U1111-1316-8548

ClinicalTrials.gov

NCT06840483

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Efficacy, Safety, Pharmacokinetic

To assess the clinical activity of zelenectide pevedotin in participants with NECTIN4 amplified tumors by the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 assessed by the Investigator.

Secondary objectives 3

1. To evaluate the safety and tolerability of zelenectide pevedotin in participants with NECTIN4 amplified tumors.
2. To assess clinical activity in participants with NECTIN4 amplified tumors by duration of response (DoR), disease control rate (DCR), clinical benefit rate (CBR), progression free survival (PFS), overall survival (OS), and by time to progression (TTP), per RECIST v1.1 assessed by the Investigator.
3. Please refer to the clinical study protocol for all Objectives.

Conditions and MedDRA coding

NECTIN4 Amplified Advanced Breast Cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. ≥ 18 years of age on day of signing informed consent
2. 2. Histologically or cytologically confirmed recurrent unresectable or metastatic TNBC or HR+/HER2-negative breast cancer as defined in cohort specific criteria.
3. 3. Confirmed NECTIN4 gene amplification by an analytically validated clinical trial assay (CTA).
4. 4. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. a. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions post irradiation.
5. 5. Archival or fresh tumor tissue comprised TNBC or HR+/HER2-negative invasive breast cancer should be available for submission to central laboratory if not provided during pre-screening
6. 6. Life expectancy ≥ 12 weeks.
7. 7. ECOG PS of ≤ 1
8. 8. Oxygen saturation of ≥93% on room air.
9. 9. Adequate organ function: a. Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for participants with Gilbert disease b. Serum albumin ≥ 2.5 g/dL c. Aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver metastases d. Alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver metastases e. Alkaline phosphatase (ALP) ≤ 2.5 × ULN or ≤ 5 × ULN in the presence of liver or bone metastases f. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation and individualized by the participant's BSA)
10. 10. International normalized ratio (INR)/prothrombin time (PT) ≤ 1.5 × ULN unless participant is receiving a stable dose of anticoagulant therapy and PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of the appropriate anticoagulants.
11. 11. Adequate bone marrow function including the following: a. Hemoglobin ≥ 9 g/dL b. Absolute neutrophil count (ANC) ≥ 1500 cells/ mm3 c. Platelet count ≥ 100,000 cells/mm3.
12. 12. Negative pregnancy test for women of childbearing potential (WOCBP) (negative serum test at Screening and negative urine or serum test within 72 hours prior to the first dose).
13. 13. WOCBP and male participants must be willing to follow highly effective contraception at least as conservative as Clinical Trial Facilitation Group (CTFG) recommendations of < 1% failure rate starting at Screening, throughout the study period, and for at least 6.5 months following the last dose of zelenectide pevedotin
14. 14. Fertile male participants must agree to refrain from sperm donation from first dose until at least 6.5 months following the last dose of zelenectide pevedotin. Women must not breastfeed or donate eggs from first dose until 6.5 months following the last dose of zelenectide pevedotin.
15. 15. Able to understand the study procedures and agree to participate in the study by providing written informed consent.
16. 16. Please refer to the study protocol for additional cohort specific criteria that may apply.

Exclusion criteria 26

1. 1. Prior treatment with any ADC containing an MMAE (vedotin) payload or other MMAE-based therapy.
2. 10. Uncontrolled hypertension (systolic blood pressure (BP) ≥ 150 mm mercury (Hg) or diastolic BP ≥ 95 mm Hg) prior to first dose.
3. 11. Active interstitial lung disease or pneumonitis requiring ongoing treatment with steroids (>10 mg per day of prednisone or equivalent) or other immunosuppressive medications.
4. 12. Ongoing clinically significant toxicity (Grade ≥ 2) associated with prior treatment for breast cancer (including radiotherapy or surgery) with the exception of well controlled immuno-oncology related endocrine disorders on supportive therapy and alopecia.
5. 13. Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS). a. Well controlled HIV will be allowed if the participant meets all the following criteria at inclusion: i. Cluster of differentiation (CD4+) counts ≥ 350 cells/μL; ii. HIV viral load < 400 copies/mL; iii. Without a history of opportunistic infection within the last 12 months; iv. On established antiretroviral therapy (ART) for at least 4 weeks.
6. 14. Known active hepatitis B, defined as positive surface antigen and/or anti-hepatitis B core antibody or positive hepatitis B polymerase chain reaction assay (a detectable hepatitis B viral load).
7. 15. Known active hepatitis C infection with positive viral load if hepatitis C virus is antibody positive (if antibody is negative then viral load is not applicable). Participants who have been treated for hepatitis C infection can be included if they have documented sustained virologic response of ≥ 12 weeks.
8. 16. Active systemic infection or fever not attributable to underlying malignancy requiring therapeutic oral or IV antibiotics within 14 days prior to first dose of study treatment. Participants receiving prophylactic antibiotics are eligible.
9. 17. Suspicion of relevant and recent systemic viral syndrome or need for quarantine/isolation that is not resolved prior to first dose of study treatment in the opinion of the Investigator.
10. 18. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s ability to take part in the full duration of the study, or is not in the best interest of the participant to take part, in the opinion of the Investigator.
11. 19. Participants with any of the following: a. A history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, congestive heart failure or symptoms of New York Heart Association (NYHA) Class III or IV documented within 6 months prior to first dose of study treatment b. Mean resting corrected QT interval (QTc) ≥ 450 msec for males, and ≥ 470 msec for females by Fridericia QT correction, except in cases of right bundle branch block or when prolongation is caused by implanted pacemaker function. c. Any factors that increase the risk of QTc prolongation such as congenital long QT syndrome, or family history of long QT syndrome. d. Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs (eg, complete left bundle branch block, third degree heart block).
12. 2. Previously tested HER2-positive (IHC 3+ or ISH+) on prior pathology testing (per ASCO-CAP guidelines)
13. 20. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
14. 21. Prior Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN)/drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), erythema multiforme, symmetric drug-related intertriginous and flexural exanthema (SDRIFE), or Baboon syndrome.
15. 22. History or another active malignancy that would interfere with the safety or efficacy evaluation of the clinical study.
16. 23. Requirement, while on study, for treatment with strong inhibitors or strong inducers of human cytochrome P450 3A (CYP3A) or inhibitors of P-glycoprotein (P-gp) including herbal- or food-based inhibitors.
17. 24. Receipt of live or attenuated vaccine within 30 days of first dose
18. 25. Prior treatment with any systemic anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to first dose of study treatment; the following exceptions are permitted: a. Palliative radiotherapy for bone or soft tissue metastasis completed > 7 days prior to baseline imaging.
19. 3. Active keratitis or corneal ulcerations.
20. 4. Known hypersensitivity or allergy to any of the ingredients of any of the study interventions, or to MMAE.
21. 5. Has not adequately recovered from recent major surgery (excluding placement of vascular access).
22. 6. Known active carcinomatous meningitis or untreated central nervous system (CNS) metastases. a. Participants with treated brain metastases may participate in the study if they are stable for at least 4 weeks prior to the first dose, either without the use of steroids or on stable or decreasing dose of ≤ 10 mg daily prednisone or equivalent and are without any symptoms that would confound the evaluation of neurologic or other adverse events (AEs).
23. 7. Uncontrolled diabetes, defined as hemoglobin A1C (HbA1c) ≥ 8%.
24. 8. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade ≥ 2 peripheral neuropathy.
25. 9. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
26. 26. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days or 5 half-lives, whichever is shorter, prior to first dose of study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR measured by the percentage of participants who have achieved either a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 assessed by the investigator.

Secondary endpoints 8

1. Incidence, severity, seriousness, relationship, and type of adverse events (AEs) and abnormalities in laboratory, electrocardiogram (ECG), vital signs, and treatment modifications.
2. DoR measured by the time from first documentation of objective response (that is subsequently confirmed) per RECIST v1.1 assessed by the Investigator to the first documentation of disease progression (per RECIST v1.1), assessed by the Investigator, or to death (due to any cause), whichever occurs first.
3. DCR measured by the percentage of participants who experience a confirmed CR, PR, or stable disease (SD) per RECIST v1.1 assessed by the Investigator.
4. CBR, defined as the proportion of participants with CR, PR or SD ≥16 weeks per RECIST v1.1 assessed by the Investigator
5. PFS measured by the time from the first day of study drug administration (Day 1) to the first documentation of disease progression (per RECIST v1.1), assessed by the Investigator, or to death (due to any cause), whichever occurs first.
6. OS measured by length of time from the first day of study drug administration (Day 1) to death (due to any cause).
7. TTP defined as the time from first dose of zelenectide pevedotin until first documentation of disease progression per RECIST v.1.1 assessed by the Investigator
8. Please refer to the clinical study protocol for all End Points.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bicycletx Limited

Sponsor organisation

Bicycletx Limited

Address

Portway Building, Granta Park, Great Abington Granta Park Great Abington

City

Cambridge

Postcode

CB21 6GS

Country

United Kingdom

Scientific contact point

Organisation

Bicycletx Limited

Contact name

BicycleTx Limited Medical Affairs

Public contact point

Organisation

Bicycletx Limited

Contact name

BicycleTx Limited Medical Affairs

Third parties 18

Locations

4 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 42 files

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

Application history

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