"TOPOLOGY" : A phase II study to evaluate the efficacy and toxicities of PLX038, in patients with locally advanced or metastatic triple-negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Curie, Institut Curie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Apr 2024 → 15 May 2025

Decision date (initial)

2023-10-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

PROLYNX

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Safety, Pharmacokinetic

Efficacy of PLX038 on response rate

Secondary objectives 6

1. Efficacy of PLX038 on TTR, DoR, PFS, OS;
2. Tolerability and safety of PLX038
3. Efficacy of PLX038 in pre-defined biomarker subgroups (BRCAness, SLFN11 expression, RB1 loss);
4. Pharmacokinetics and pharmacodynamics effect of PLX038.
5. Exploratory: To explore biomarkers of response of PLX038 (exploratory)
6. Exploratory: Efficacy according to central radiological review

Conditions and MedDRA coding

Advanced or metastatic triple-negative breast cancer

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Willing and able to comply with the protocol and provide written informed consent prior to study-specific screening procedures
2. Age ≥ 18 years
3. Females and males with cytologically or histologically confirmed breast carcinoma (either the primary or metastatic lesions)
4. Locally advanced or metastatic disease that is not amenable to curative treatment
5. Triple negative breast cancer (both ER and PR <10%, HER2-negative or HER2-low)
6. Measurable disease (per RECIST version 1.1)
7. Prior therapy (administered in the neoadjuvant, adjuvant and/or metastatic setting) with an anthracycline, taxane and sacituzumab-govitecan (unless not medically appropriate or contraindicated for the patient)
8. Received a minimum of two prior cytotoxic chemotherapy regimens for locally advanced or metastatic breast cancer
9. Patients with known gBRCA mutations must have received a PARP inhibitor in the metastatic setting.
10. Patients whose cancer has a CPS score ≥10 must have received prior pembrolizumab unless (i) contra-indicated (ii) CPS score or pembrolizumab not available at time of first line treatment start
11. Resolution of chemotherapy and radiation therapy related toxicities to NCI-CTCAE version 5.0 Grade 1 or lower severity, except for stable sensory neuropathy (≤ Grade 2), alopecia (any grade), presence of clinically managed chronic autoimmune AEs from prior immune therapy
12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
13. Adequate organ function (obtained within 14 days prior to treatment start) as evidenced by: i. Absolute neutrophil count (ANC) ≥ 1.5 X 109/L; ii. Hemoglobin (Hgb) ≥ 9 g/dL; iii. Platelet count ≥ 100 X 109/L; iv. Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with a documented history of Gilbert’s disease (≤ 2 X ULN); v. Alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤ 2.5 X ULN (for patients with liver metastases ≤ 5 X ULN); vi. Alkaline phosphatase (AP) ≤ 3 X ULN (for patients with liver metastases, ≤ 5 X ULN); vii. Serum creatinine ≤ 1.5 mg/dL (133 μmol/L) or calculated creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula); viii. Women of childbearing potential (WCBP): negative serum pregnancy test
14. Patients covered by social security or health insurance in compliance with the national legislation relating to biomedical research

Exclusion criteria 13

1. Patients who had a last dose of IV chemotherapy within 21 days, last dose of oral cytotoxic chemotherapy, radiotherapy, biological therapy, or investigational therapy within 14 days prior to treatment start
2. Patients who had any major surgery within 28 days prior to inclusion
3. Patients with chronic inflammatory bowel disease and/or bowel obstruction
4. Concomitant use of other agents for the treatment of cancer or any investigational agent(s)
5. Brain metastases, unless local therapy was completed and use of corticosteroids for this indication discontinued for at least 3 weeks prior to inclusion. Signs or symptoms of brain metastases must be stable for at least 28 days prior to inclusion. No known progression of brain metastases (by imaging as assessed by RECIST) can have occurred. Patients with leptomeningeal disease or meningeal carcinomatosis are excluded
6. Women who are either pregnant, lactating, planning to get pregnant
7. Patients receiving pharmacotherapy for hepatitis B or C, tuberculosis, or HIV
8. Patients with known liver disease diagnosed with Child-Pugh A or higher cirrhosis
9. Prior stage III or IV malignancy (other than breast cancer)
10. Severe/uncontrolled intercurrent illness within the previous 28 days prior to inclusion
11. Significant known cardiovascular impairment (NYHA CHF > grade 2, unstable angina, myocardial infarction within the previous 6 months prior to inclusion, or existing unstable cardiac arrhythmia)
12. Any other significant medical, psychological, social or geographic conditions that in the opinion of the Investigator would impair study participation or cooperation
13. Patients deprived of their liberty or under guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria)

Secondary endpoints 6

1. Time to response (TTR), Duration of Response (DoR), Progression free survival (PFS) and Overall Survival (OS)
2. AEs and SAEs (all grade, per NCI-CTCAE v5.0)
3. Association between PLX038 efficacy and homologous recombination (HR) defect (assessed by HR genes mutational status and BCRAness phenotype), replication stress-related biomarkers such as SFLN11 expression, RB1 loss
4. PK/PD analysis
5. Exploratory: Association between PLX038 efficacy and tumor or blood biomarkers.
6. Exploratory: Centrally determined ORR and PFS.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Public contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Public contact point

Organisation

Institut Curie

Contact name

François-Clément BIDARD

Sponsor responsibilities

Article 77 compliance

Institut Curie

Contact point sponsor

Institut Curie

Article 77 implementation

Institut Curie

Locations

1 EU/EEA country · 2 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

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

Application history

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