Safety and efficacy analysis of an antibody associated with a chemotherapy for patients with a triple negative metastatic 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]

Trial duration

2 Oct 2023 → ongoing

Decision date (initial)

2023-02-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences

External identifiers

EU CT number

2022-502369-10-00

ClinicalTrials.gov

NCT05552001

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Safety

To evaluate the efficacy of sacituzumab govitecan via investigator-assessed objective response rate (ORR) according to RECIST v1.1, in patients with mTNBC or inoperable locally ABC whose disease has progressed on (neo)adjuvant chemotherapy for early TNBC or within 6 months after the end of curative treatments (any systemic or local treatment with curative intent, whatever comes last).

Secondary objectives 3

1. Efficacy: To evaluate the efficacy of sacituzumab govitecan in terms of: • Progression-free survival (PFS); • Duration of response (DOR); • Clinical benefit rate (CBR); • Overall survival (OS). And to study all the efficacy endpoints in subgroups defined by previous treatment lines.
2. Safety: To evaluate the safety of sacituzumab govitecan: • in the overall population; • in patients homozygous for the UGT1A1*28 allele and other polymorphisms affecting the expression of UGT1A1.
3. Exploratory objectives: • To describe TROP-2 expression levels and gene-expression profiling during treatment with sacituzumab govitecan (by IHC, multiplexed immune-fluorescence and HTG EdgeSeq) by assessing TROP-2 expression at baseline/on-treatment and at progression in the whole cohort and by matching samples of the same patients • To identify biomarkers associated to treatment response/resistance (including TACSTD2 and TOP-I mutations) • To assess sacituzumab govitecan modulation on circulating tumor cells (CTCs) • To explore immune effects associated with SG

Conditions and MedDRA coding

Triple negative metastatic breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patient must have signed a written informed consent prior to any trial specific procedures; Note; When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
2. Male or female ≥ 18 years of age;
3. Patients with pathologically documented locally advanced inoperable or metastatic triple negative breast cancer (mTNBC) whose disease has progressed on (neo)adjuvant chemotherapy+/-immunotherapy for early TNBC or within 6 months after the end of any systemic therapy, surgery or radiotherapy with curative intent, whatever comes last.
4. Prior exposure to a taxane in localized or advanced/metastatic setting; Note: If indicated, prior therapy with ICI for patients with PD1 positive tumor and prior treatment with PARP inhibitor for patients with gBRCAm is required
5. Measurable disease, as defined by RECIST v1.1
6. Patient must have accepted to perform on-treatment biopsie. If the physician considers doing the biopsy on the primary tumor site because accessibility, it can be performed only if the primary tumor site has not been previously irradiated;
7. Have metastatic site easily accessible to biopsy (with exception of bone metastasis) Note 1 : Patients with only bone metastasis will be eligible if the primary tumor is accessible for on treatment biopsy. Note 2 : If the patient has a single measurable lesion and it is the only one that can be biopsied, the patient cannot be included because the disease is no longer measurable according to RECIST v1.1
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
9. Life expectancy ≥12 weeks;
10. Adequate haematologic and organ function: Hematologic counts : Hemoglobin ≥9 g/dL, Absolute neutrophil count ≥1500/mm3 or ≥1.5 x 109/L Platelets ≥100,000/μL (without transfusional or growth factor support within 2 weeks of study drug initiation) Serum creatinine (SCr) ; Creatinine clearance (CrCl) ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl; Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) : AST and ALT ≤ 2.5 ULN or ≤ 5 ULN if known liver metastases; Total bilirubin : ≤1.5 × upper limit of normal (ULN) if no liver metastases (<3 × ULN in the presence of documented Gilbert’s Syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline); Serum albumin : >3 g/dL
11. Negative hepatitis B surface antigen (HBsAg) test at screening (patients with a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test at screening are eligible), negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening;
12. Evidence of post-menopausal status or negative pregnancy urinary test within 72 hours or serum pregnancy test within 14 days of before study treatment and confirmed prior to treatment on Cycle 1 Day 1 for female pre-menopausal patients;
13. Woman of childbearing potential and male patient must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment for women and up to 3 months for men;
14. Patient affiliated to a social security system (or equivalent);
15. Patient is 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 20

1. Participation in another therapeutic trial within the 30 days prior to C1D1;
2. Patients with unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved according to the common terminology criteria for adverse events of the National Cancer Institute (NCI-CTCAE) v5.0 grade >2
3. Treatment with systemic corticosteroids dosed at >20 mg prednisone or equivalent or other systemic immunosuppressive medications within 2 weeks prior to C1D1;
4. Known history of testing positive for HIV or known acquired immunodeficiency syndrome;
5. Known COVID-19 infection at screening;
6. Evidence of significant uncontrolled concomitant disease;
7. Individuals with physical or psychological conditions considered not to be compatible with the trial;
8. Persons deprived of their liberty or under protective custody or guardianship;
9. Pregnant or breastfeeding women;
10. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
11. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases or evidence of leptomeningeal disease or clinically active spinal cord compression. Patients with stable and asymptomatic brain metastases will be eligible, yet the number will be capped to 15% of the overall population;
12. Previous history of cancer other than mTNBC within 5 years prior to C1D1, except of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and treated with curative intent (e.g. carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer);
13. Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrolment. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c) NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%.
14. Severe uncontrolled infection requiring oral or IV antibiotics within 4 weeks prior to C1D1;
15. Major surgical procedure within 4 weeks prior to C1D1;
16. History of severe allergic, anaphylactic, or other hypersensitivity reactions to humanized antibodies;
17. Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
18. Patients receiving concomitant anti-cancer treatments such as chemotherapy, immunotherapy, endocrine therapy and radiotherapy;
19. Prior treatment with topoisomerase-1 inhibitor or with ADC containing topoisomerase-1 inhibitor
20. Requirement for ongoing therapy with medications that are prohibited or to be used with caution

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is anti-tumor activity of sacituzumab govitecan (SG) measured by the objective response rate (ORR) based on investigator assessment. ORR is defined as the number of patients with at least a confirmed complete response (CR) or partial response (PR), based on the best objective response values while not having started a new anticancer therapy. Treatment objective response will be radiologically assessed every 6 weeks using RECIST v1.1.

Secondary endpoints 9

1. Efficacy: • PFS is defined as the time from date of first dose until the date of the first objective documentation of disease progression (PD) or death from any cause, whichever occurs first. For patients without documented radiological progression, follow-up will be censored at the date of last radiological assessment without progression, unless death occurs within 12 weeks following the date last known progression-free, in which case the death will be counted as a PFS event.
2. Efficacy: • DOR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of PD or death due to any cause.
3. Efficacy: • CBR is defined as the presence of at least a PR or CR, or a stable disease (SD) while not having started a new anticancer therapy.
4. Efficacy: • OS is defined as the time from date of first dose until death. Patients alive at last follow-up will be censored at this date.
5. Safety: Safety and tolerability of sacituzumab govitecan will be evaluated through: frequency and severity of any adverse events (AEs), serious adverse events (SAEs) graded by NCI-CTCAE v5.0; proportion of treatment discontinuation, interruptions and dose reductions due to any AEs;
6. Exploratory endpoints: • Evaluation of TROP-2 dynamics and correlation with payload delivery and efficacy using biopsies at baseline, on-treatment and at progression
7. Exploratory endpoints: • Genomic alterations of interest through whole exome sequencing (WES) and HTG-Edge Seq on tumor and ctDNA samples collected pretreatment and upon progression
8. Exploratory endpoints: • Determination of CTCs levels at baseline and tumor CTCs phenotype to assess tumor heterogeneity and to evaluate the predictive value of CTCs on the objective response and survival
9. Exploratory endpoints: • Determination of SG impact on tissue-resident memory T (TRM) cells, myeloid cells, and other immune cells; immunogenic cell death (ICD) associated to SG treatment

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris Cedex 13

Postcode

75654

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Public contact point

Organisation

Unicancer

Contact name

Director of regulatory Affairs and Pharmacovigilance

Locations

2 EU/EEA countries · 20 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

Documents 15 files

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

Application history

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