Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

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 \[NCI-CTCAE, Version 5\].

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.

PLX038

Fouzia Azzouz

François-Clément Bidard, Study Principal Investigator

François-Clément Bidard

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.

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.

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

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

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

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

Time to response is defined as the time from inclusion to the first objective tumor response and will be estimated using Kaplan-Meier method

Serious adverse events (SAEs)according to NCI CTCAE v5.0, by grade and their relationship to PLX038

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (BRCAness)

Maximum Plasma Concentration effect of PLX038

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

PFS is defined as the time from inclusion to progression (per RECIST 1.1) or death, among included patients

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.

Adverse events (AEs) according to NCI CTCAE v5.0, by grade and their relationship to PLX038

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (SLFN11 expression)

Incidence of efficacy of PLX038 in pre-defined biomarker subgroups (RB1 loss)

Maximum Plasma Concentration of effect of PLX038

ProLynx LLC

Institut Curie

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Carboplatin

Ixazomib

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Accelerated dose-escalation phase with a single-patient cohort per dose level until defined DLT is observed during cycle 1, or until dose level 4 is reached. At this dose level the cohort is expanded to three patients and dose escalation reverts to a conventional 3+3 escalation design.

Intervention (experimental): Ixazomib; po; 3mg escalated to 4mg; day 1, 8, 15 Intervention (backbone): AUC 1.5 escalated to AUC 2.5; day 1, 8, 15

Cycles will be repeated every four weeks. All subjects will continue on study drug until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

Cycles will be repeated every four weeks. Cycles will be repeated every four weeks. All subjects will continue on study drug until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

Richard Greil, MD

This is an open-label phase I/II study for patients with advanced (locally advanced inoperable or metastatic) triple-negative breast cancer progressing after first-line therapy receiving ixazomib on days 1, 8, and 15 in combination with carboplatin on days 1, 8, and 15. Cycles will be repeated every four weeks.

The phase I part of this study uses an alternate dose escalation accelerated titration design. In the accelerated dose-escalation phase a single-patient cohort per dose level will be enrolled, until one dose limiting toxicity (DLT) or 2 moderate toxicities are observed during cycle 1, or until dose level 4 is reached. At this dose level the cohort is expanded to three patients and dose escalation reverts to a conventional 3+3 escalation design.

DLTs are defined as inability to deliver the drug combination of ixazomib and carboplatin due to drug related toxicity.

The maximum-administered dose (MAD) is defined as the dose at which DLT occur in at least two of six patients treated at that dose level. The dose just below the MAD is considered the maximum-tolerated dose (MTD), providing that DLT is observed in fewer than two of six treated patients (or fewer than one third if more than six patients will be treated) at that dose level. Determination of MAD and MTD is based on DLT observed during the first treatment cycle.

Phase II:

After establishing MTD in phase I, accrual continues to evaluate the efficacy and safety of the combination. A total of 41 patients will be included (patients enrolled in the phase I part within the conventional dose escalation phase at the dose level considered as the MTD may be included).

All subjects will continue on study drugs until disease progression, unacceptable toxicity or treatment discontinuation for any other reason.

Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer

Determination of maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs)

Incidence, type, severity and consequences (e.g. study discontinuation) of an adverse event

Complete remission, partial remission or stable disease for at least 24 weeks

EORTC quality of life questionnaire (QLQ-C30 and QLQ-BR23)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Evaluate the Efficacy and Toxicities of PLX038, in Patients With Locally Advanced or Metastatic Triple-negative Breast Cancer	NCT06162351	Breast Cancer	PLX038	18 Years -	Institut Curie
Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer	NCT02993094	Triple-Negative...	Ixazomib Carboplatin	18 Years -	Arbeitsgemeinschaft medikamentoese Tumortherapie

Spots Global Cancer Trial Database for advanced triple negative