A randomized, double-blinded, placebo-controlled, multicenter, phase II/III efficacy and safety study of oral TherO2-01S22 as add-on therapy on top of first line anti-HER2 targeted treatment of patients with Metastatic Breast Cancer TherO2-01S22 in HER2-positive breast cancer: TherO2-MBC Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Regional Lutte Contre Le Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-10-03

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516576-15-00

ClinicalTrials.gov

NCT05698186

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

(Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of Objective response rate (ORR).

Secondary objectives 7

1. (Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of Progression-Free Survival (PFS)
2. (Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of Overall Survival (OS)
3. (Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of safety
4. (Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of cardiotoxicity
5. (Phase III) To compare the effects of anti-HER2 targeted containing regimen with and without oral TherO2-01S22 in terms of quality of life
6. (Phase III) To characterize exposure of oral TherO2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer
7. (Phase III) To characterize modification of trastuzumab/pertuzumab pharmacokinetics parameters during exposure to oral TherO2-01S22 when administered as add-on therapy on top of first line anti-HER2 targeted treatment of patients with metastatic breast cancer

Conditions and MedDRA coding

metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Women or men aged more than or equal to 18 years old
2. Metastatic setting of a histologically confirmed adenocarcinoma of the breast
3. Overexpression of HER2 in the primary tumor or a metastatic lesion (3+ by ICH or 2+ with confirmation of positivity by FISH or SISH)
4. Performance status = 0, 1 or 2
5. Metastatic disease requiring the initiation of an anti HER2 containing regimen
6. First line treatment for metastatic disease
7. Patients for whom a minimum of 3-month life expectancy is anticipated
8. Baseline LVEF value > 50%, measured by cardiac MRI, by echocardiography (Simpson’s method) or by MUGA scan within 7 days before randomization. According to trastuzumab and pertuzumab Summary of Product Characteristics
9. Informed consent form signed
10. Initial serum calcium and fasting blood glucose levels must be normal

Exclusion criteria 12

1. Patients not eligible for anti-HER2 therapy
2. Persons receiving psychiatric medical care
3. Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice)
4. Patients previously treated at the metastatic setting by systemic treatment
5. Serious cardiac illness or medical conditions disallowing administration of anti-HER2 therapy. According to trastuzumab and pertuzumab SPCs
6. Known hypersensitivity to trastuzumab, pertuzumab, TherO2-01S22, murine proteins or to any of the excipients
7. Spinal cord compression and/or symptomatic or progressive brain metastases (Brain metastasis are not acceptable unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug).
8. Patients who, for social, geographic or psychological reasons, cannot be adequately followed up and/or are incapable of undergoing regular controls
9. Pregnant or breastfeeding women
10. People with diabetes
11. Persons deprived of liberty by judicial or administrative decision
12. Persons not affiliated to a social security system or equivalent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR): Percentage of patients whose disease decreased (Partial Response, PR) and / or disappears (Complete Response, CR) after treatment, according to RECIST V1.1 criteria20 and according to the adapted EORTC criteria for 18F-FDG PET-scan : Time Frame: at D43

Secondary endpoints 7

1. Progression-Free Survival (PFS): defined as the time interval from the date of randomization to the date of progression. Events considered as progression include local or distant progression, appearance of a second cancer or death (all causes) whichever occurs first. Time Frame: every 3 months up to 24 months from randomization
2. Overall Survival (OS): defined as the time interval from the date of randomization to the date of death, regardless of disease progression. Time Frame: every 3 months up to 24 months from randomization
3. Safety: Incidence of treatment-related adverse events (AEs) and serious adverse events (SAEs) classified according to the CTCAE v5.0 criteria. Record of all AEs (regardless of imputability) until the safety visit. Time Frame: from randomization to D64
4. Cardiotoxicity: defined by decrease in Left Ventricular Ejection Fraction (LVEF) value according to the modality performed (cardiac MRI, MUGA scan or echocardiography) and any other cardiac toxicities revealed by physical examination or any other adequate exam (CTCAE v5.0 criteria). Time Frame: every 3 months up to 24 months from randomization
5. Quality of life: QLQ-C30 and BR23 auto-questionnaire Time Frame: at baseline and D43
6. Summary of oral TherO2-01S22 pharmacokinetics parameters. PK samples to be collected before IMP or placebo intake, and at 15, 30, 45, 60, 120, 240, 300 min after the intake as detailed in section 10.1. Time Frame: at D-1 of cycle 1 and cycle 2
7. Summary of trastuzumab/pertuzumab pharmacokinetics parameters. PK samples to be collected prior to trastuzumab/pertuzumab administration as detailed in section 10.2. Time Frame: at D1 of cycle 2 and at D43 (corresponding to the day 1 of cycle 3 of trastuzumab/pertuzumab

Investigational products

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

Test 1

Comparator 5

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Regional Lutte Contre Le Cancer

Sponsor organisation

Centre Regional Lutte Contre Le Cancer

Address

3 Rue De La Porte De L Hopital

City

Strasbourg

Postcode

67000

Country

France

Scientific contact point

Organisation

Centre Regional Lutte Contre Le Cancer

Contact name

BENDER-SOMME

Public contact point

Organisation

Centre Regional Lutte Contre Le Cancer

Contact name

BENDER-SOMME

Locations

1 EU/EEA country · 3 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 29 files

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

Application history

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