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A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer (TOPOLOGY)

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ClinicalTrials.gov Identifier: NCT06162351
Recruitment Status : Recruiting
First Posted : December 8, 2023
Last Update Posted : May 20, 2024
Sponsor:
Collaborator:
ProLynx LLC
Information provided by (Responsible Party):
Institut Curie

Brief Summary:
Single arm phase II study for with primary objective to evaluate the efficacy of PLX038 on response rate for patients with pretreated, metastatic or locally advanced triple negative breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: PLX038 Phase 2

Detailed Description:

This is an open label, multi-centric phase II study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of PLX038 in locally-advanced or metastatic TNBC. Patient must have received 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) and Received a minimum of two prior cytotoxic chemotherapy regimens for locally advanced or metastatic breast cancer.

Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for > 5 days or ANC < 100 109/L for more than 1 day, or other non-hematological toxicities of Grade > 2 [NCI-CTCAE, Version 5].

All included patients will receive PLX038 as single agent as long as study is ongoing or until progression of disease, unacceptable toxicity, patient withdrawal of consent, Investigator decision, lost to follow-up, death, patient non-compliance, or study termination by Sponsor.

Tumor assessments must be performed according to the RECIST V1.1 criteria at inclusion and every 8 weeks (± 7 days) from inclusion until documented disease progression, withdrawal of consent, or death. Radiographic measurements must be performed to the RECIST specifications.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm phase II study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer
Actual Study Start Date : April 17, 2024
Estimated Primary Completion Date : August 19, 2025
Estimated Study Completion Date : March 19, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Single arm: treatment with PLX038
Patients will be treated at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2. At the discretion of the treating physician, the PLX038 dose will be increased to 1730 mg/m2 for patients who tolerate at least 1 cycle without any of the following toxicities: febrile neutropenia, grade 4 neutropenia for > 5 days or ANC < 100 109/L for more than 1 day, or other non-hematological toxicities of Grade > 2 [NCI-CTCAE, Version 5].
Drug: PLX038

Study treatment will be at a dose of 1730mg/m2 IV infusion on Day 1 of each cycle Q3W (every 21 days, 1 cycle = 1 injection) after at least a first cycle at 1300mg/m2.

Patients with a clinical benefit could be treated as long as study is ongoing. Patients are followed from inclusion until documented disease progression, withdrawal of consent, or death.





Primary Outcome Measures :
  1. Best tumor response [ Time Frame: 24 weeks ]
    Best tumor response (defined as PR or CR in the first 6 months of treatment, assessed by investigators per RECIST v1.1 criteria).


Secondary Outcome Measures :
  1. Time to response (TTR) [ Time Frame: Until 24 months ]
    Time to response is defined as the time from inclusion to the first objective tumor response and will be estimated using Kaplan-Meier method

  2. SAEs (all grade, per NCI-CTCAE v5.0) [ Time Frame: Until 30 days after the last dose of IMP (24 months + 30 days) ]
    Serious adverse events (SAEs)according to NCI CTCAE v5.0, by grade and their relationship to PLX038

  3. Correlation between PLX038 efficacy and homologous recombination (HR) defect (assessed by HR genes mutational status and BCRAness phenotype) [ Time Frame: Until 24 months ]
    Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (BRCAness)

  4. PK analysis [ Time Frame: Until 24 months ]
    Maximum Plasma Concentration effect of PLX038

  5. Duration of Response (DoR) [ Time Frame: Until 24 months ]
    DoR is defined as the time from the first documented PR or CR until the date of disease progression or the date of death. DoR will be computed using Kaplan-Meier

  6. Progression free survival (PFS) [ Time Frame: Until 24 months ]
    PFS is defined as the time from inclusion to progression (per RECIST 1.1) or death, among included patients

  7. Overall Survival (OS) [ Time Frame: Until 24 months ]
    PFS is defined as the time from inclusion to the first event among progression and death. OS is defined in the same way but only death is taken into account.

  8. AEs [ Time Frame: Until 30 days after the last dose of IMP (24 months + 30 days) ]
    Adverse events (AEs) according to NCI CTCAE v5.0, by grade and their relationship to PLX038

  9. Correlation between PLX038 efficacy and homologous recombination (HR) defect, replication stress-related biomarkers such as SFLN11 expression [ Time Frame: Until 24 months ]
    Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (SLFN11 expression)

  10. Correlation between PLX038 efficacy and homologous recombination (HR) defect replication stress-related biomarkers such as RB1 loss [ Time Frame: Until 24 months ]
    Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (RB1 loss)

  11. PD analysis [ Time Frame: Until 24 months ]
    Maximum Plasma Concentration of effect of PLX038



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing and able to comply with the protocol and provide written informed consent prior to study-specific screening procedures.
  • Age ≥ 18 years.
  • Females and males with cytologically or histologically confirmed breast carcinoma (either the primary or metastatic lesions).
  • Locally advanced or metastatic disease that is not amenable to curative treatment.
  • Triple negative breast cancer (both ER and PR <10%, HER2-negative or HER2-low).
  • Measurable disease (per RECIST version 1.1).
  • 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).
  • Received a minimum of two prior cytotoxic chemotherapy regimens for locally advanced or metastatic breast cancer.
  • Patients with known gBRCA mutations must have received a PARP inhibitor in the metastatic setting.
  • 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.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • 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.

  • Patients covered by social security or health insurance in compliance with the national legislation relating to biomedical research.

Exclusion Criteria:

  • 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.
  • Patients who had any major surgery within 28 days prior to inclusion.
  • Patients with chronic inflammatory bowel disease and/or bowel obstruction.
  • Concomitant use of other agents for the treatment of cancer or any investigational agent(s).
  • 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.
  • Women who are either pregnant, lactating, planning to get pregnant.
  • Patients receiving pharmacotherapy for hepatitis B or C, tuberculosis, or HIV.
  • Patients with known liver disease diagnosed with Child-Pugh A or higher cirrhosis.
  • Prior stage III or IV malignancy (other than breast cancer).
  • Severe/uncontrolled intercurrent illness within the previous 28 days prior to inclusion.
  • 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).
  • Any other significant medical, psychological, social or geographic conditions that in the opinion of the Investigator would impair study participation or cooperation.
  • Patients deprived of their liberty or under guardianship.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06162351


Contacts
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Contact: Fouzia Azzouz 0147112366 fouzia.azzouz@curie.fr
Contact: François-Clément Bidard, Study Principal Investigator

Locations
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France
Institut Curie Recruiting
Paris, France, 75248 Cedex
Contact: François-Clément Bidard       francois-clement.bidard@curie.fr   
Principal Investigator: François-Clément Bidard         
Institut Curie Recruiting
Saint Cloud, France, 92210
Contact: François-Clément Bidard       francois-clement.bidard@curie.fr   
Principal Investigator: François-Clément Bidard         
Sponsors and Collaborators
Institut Curie
ProLynx LLC
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Responsible Party: Institut Curie
ClinicalTrials.gov Identifier: NCT06162351    
Other Study ID Numbers: IC 2020-16
First Posted: December 8, 2023    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Institut Curie:
Pretreated
Metastatic
Locally
Advanced triple negative
Additional relevant MeSH terms:
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Triple Negative Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases