Testing two different drugs (sacituzumab-govitecan and trastuzumab-deruxtecan) combinations prescribed in an alterning pattern to patients with metastatic or locally advanced triple-negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-10-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

INCA (PHRC-K24-045)

External identifiers

EU CT number

2025-521909-40-00

ClinicalTrials.gov

NCT07151586

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To demonstrate the superiority in terms of overall survival of the SG and T-DXd combinations in an upfront alternating scheme as first line of antibody-drug conjugates in HER2-low mTNBC over SG alone.

Secondary objectives 7

1. Efficacy : To compare the clinical benefit rate (CBR) between the alternating regimen and sacituzumab govitecan monotherapy.
2. Efficacy : To describe PK/PD of ADCs in the alternating scheme.
3. Safety and Quality of life : To evaluate the safety and tolerability of the alternating regimen compared with the control arm (sacituzumab govitecan monotherapy)
4. Safety and Quality of life : To compare the quality of life between the alternating regimen (sacituzumab govitecan and Trastuzumab deruxtecan) and sacituzumab govitecan monotherapy.
5. Efficacy : To compare the objective response rate (ORR) between the alternating regimen and sacituzumab govitecan monotherapy.
6. Efficacy : To compare progression-free survival (PFS) between the alternating regimen and sacituzumab govitecan monotherapy.
7. Efficacy : To compare quality-adjusted progression-free survival (QA-PFS) between the alternating regimen and sacituzumab govitecan monotherapy.

Conditions and MedDRA coding

Patients with metastatic or locally advanced HER2-low triple-negative breast cancer and eligible to receive sacituzumab-govitecan and T-Dxd according to their indication.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patient must have signed a written informed consent prior to any trial specific procedures.
2. Men or women ≥ 18 years of age;
3. Histologically confirmed metastatic or locally advanced and unresectable triple negative breast cancer that meets both of the following criteria by local testing: • HER2-low breast cancer (BC) with documented evidence of HER2-low defined as: [immunohistochemistry (IHC) 2+/in situ hybridization (ISH)- or IHC 1+ (ISH- or untested)] on either the primary or any metastatic site • With Estrogen Receptor expression <10% AND Progesterone Receptor expression <10%,
4. Patient eligible to receive sacituzumab-govitecan and T-Dxd according to their indication
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
6. Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of trial participation and up to 7 months after completing the study treatment for women and up to 4 months for men..
7. Adequate organ and bone marrow functions within 28 days before enrollment. For all parameters listed below, the most recent results available must be used • Hemoglobin ≥ 9 g/dL. Note: Red blood cell transfusion is not allowed within 1 week prior to screening assessment. • Absolute neutrophil count (ANC) ≥ 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment. • Platelet count ≥ 100,000/mm3. Note: Platelet transfusion is not allowed within 1 week prior to registration. • Total bilirubin ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastasis at baseline. • Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3 ×ULN or < 5 × ULN in patients with liver metastasis. • Serum albumin ≥ 2.5 g/dL. • Creatinine clearance (CrCl) ≥ 30 mL/min (calculated using the Cockcroft and Gault equation). Cockcroft-Gault equation: CrCl (mL/min) = [140 - age (years)] × weight (kg) 72 × serum creatinine (mg/dL) {× 0.85 for females}.
8. Adequate cardiac function, defined as a left ventricular ejection fraction ≥ 55% estimated by echocardiogram or multigated acquisition scintigraphy.
9. Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization.
10. Affiliated to the French Social Security System (or equivalent).
11. Patient willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits, and examinations including follow-up.

Exclusion criteria 12

1. Previously treated with any ADC targeting HER2 or TROP2
2. Uncontrolled or significant cardiovascular disease
3. Patients with brain metastases (BM) except for asymptomatic treated BM not requiring ongoing corticosteroid treatment with stable lesions on baseline/screening brain MRI. Patients who require treatment of brain metastases are eligible after 14 days post surgery or radiation, if felt to be clinically stable and not requiring ongoing corticosteroid treatment
4. History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
5. Any medical history or condition that per protocol or in the opinion of the investigator is incompatible with the study.
6. Patients with known allergy or severe hypersensitivity to any of the trial drugs or their excipients
7. Other concurrent medical or psychiatric condition that, in the Investigator's opinion, may cause misleading study interpretation or prevent completion of study procedures and followup examinations.
8. Patients with any other disease or illness which requires hospitalisation or is incompatible with the trial treatment are not eligible.
9. Patients enrolled in another therapeutic trial within 30 days of inclusion
10. Pregnant or breast-feeding women at the time of randomization or intention to become pregnant during the study and up to 7 months after treatment
11. Person deprived of their liberty or under protective custody or guardianship
12. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival estimated by the Kaplan-Meier method will be used as primary efficacy outcome. Overall survival is defined as the interval between the date of randomization and the date of death from any cause. Alive patients will be censored at the date of last follow-up.

Secondary endpoints 6

1. Efficacy : The clinical benefit rate (CBR), defined as the percentage of patients with a complete response (CR, defined as a disappearance of all target lesions), a partial response (PR, defined as at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease for at least 24 weeks
2. Efficacy : Objective response rate (ORR), defined as the percentage of patients with a complete response (CR, defined as a disappearance of all target lesions) or a partial response (PR, defined as at least a 30% decrease in the sum of diameters of target lesions).
3. Efficacy : The progression-free survival (PFS), defined as the interval between the date of randomization and the date of progression or death from any cause, whichever occurs first. A patient alive and without progression will be censored at the date of last follow-up.
4. Efficacy : Quality adjusted PFS (QA-PFS) calculated as the product of the PFS function and the overall health utility index EQ-5D-5L.
5. Safety and Quality of life : Safety and tolerability of sacituzumab govitecan will be evaluated by the frequency and severity of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs) graded according to the NCI-CTCAE v5.0; The proportion of treatment discontinuations, interruptions and dose reductions due to any AEs will also be measured.
6. Safety and Quality of life : Mean changes from Baseline in Global Health Status/Quality of Life (GHS/QoL) will be measured at week 24 via the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30).

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 19 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 10 files

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

Application history

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