Sacituzumab Govitecan in primary HER2-negative breast cancer (SASCIA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

GBG Forschungs GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Oct 2020 → ongoing

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Gilead Sciences, Inc.

External identifiers

EU CT number

2023-510390-33-00

EudraCT number

2019-004100-35

ClinicalTrials.gov

NCT04595565

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacogenetic, Therapy

To compare invasive disease free survival (iDFS) between patients
treated with sacituzumab govitecan vs. treatment of physician's choice.

Secondary objectives 9

1. To compare overall survival (OS) between both groups.
2. To compare distant disease-free survival (DDFS) between both groups.
3. To compare the invasive breast cancer-free survival (iBCFS) between both groups.
4. To compare locoregional recurrences-free interval (LRRFI) between both groups.
5. To compare iDFS and OS in stratified subgroups: HR-negative vs. HR-positive; ypN+ vs. ypN0
6. To compare iDFS and OS in exploratory subgroups: Prior platinum therapy (TNBC); Prior immune-checkpoint inhibitor therapy (TNBC); Experimental arm vs. active TPC in TNBC, overall and in subgroups of different active TPC; low vs. high TROP2-expression (cut off will be defined in the SAP)
7. To compare safety between both groups.
8. To assess and compare compliance on the treatment between both arms.
9. To assess Patient Reported Outcome (PRO) and Quality of Life (QoL) between both groups.

Conditions and MedDRA coding

HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Women or men with age at diagnosis at least 18 years.
2. Patients with known gBRCA1/2 mutation without indication to adjuvant olaparib therapy are allowed to participate in the trial.
3. An interval of less than 16 weeks since the date of final surgery or less than 10 weeks from completing radiotherapy (whichever occurs last) and the date of randomization is required.
4. Radiotherapy should be delivered before the start of study treatment. Radiotherapy to the breast is indicated in all patients with breast conserving surgery and to the chest wall and lymph nodes according to local guidelines as well as in all patients with cT3/4 or ypN+ disease treated by mastectomy.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
6. Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedure or radiotherapy to NCI CTCAE v 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patients at the investigator´s discretion).
7. Normal cardiac function after neoadjuvant chemotherapy must be confirmed according to local guidelines. Results for LVEF must be above the normal limit of the institution.
8. Laboratory requirements within range as specified in the protocol: hematology (ANC ≥1.5 x 10^9 / L; platelets ≥100 x 10^9 / L; hemoglobin ≥10 g/dL (≥6.2 mmol/L)), hepatic function (total bilirubin <1.25x UNL; AST and ALT ≤1.5x UNL; alkaline phosphatase ≤2.5x UNL), renal function (<1.25x ULN creatinine or creatinine clearance ≥30 ml/min (according to Cockroft-Gault, if creatinine is above UNL)).
9. Negative pregnancy test (urine or serum) within 14 days prior to randomization for all women of childbearing potential.
10. For women of childbearing potential and males with partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for a specified period after the last dose as specified in the protocol.
11. Complete staging work-up prior to the initiation of neoadjuvant chemotherapy. Missing staging investigations must be performed prior to randomization.
12. Formalin fixed paraffin embedded tissue (FFPE) block from surgery after neoadjuvant chemotherapy and from biopsy (excluding excisional biopsy or lumpectomy) preferably of the breast, before start of neoadjuvant chemotherapy. For patients with bilateral carcinoma, FFPE blocks from both sides have to be provided for central testing.
13. Histologically confirmed unilateral or bilateral primary invasive carcinoma of the breast, confirmed histologically by core biopsy. The lead tumor has to be defined by the investigator based on the inclusion criteria for the respective subtype and on the risk status.
14. Centrally confirmed HER2-negative (IHC score 0-1 or FISH negative according to ASCO/CAP guideline) and either: HR-positive (≥1% positive stained cells) disease or HR-negative (<1% positive stained cells), assessed preferably on tissue from postneoadjuvant residual invasive disease of the breast, or if not possible, of residual nodal invasion. If not evaluable, core of diagnostic biopsy will be used. In case of bilateral breast cancer, HER2-negative status has to be confirmed for both sides.
15. Patients with residual invasive disease after neoadjuvant chemotherapy at high risk of recurrence defined as follows: any residual invasive disease > ypT1mi and/or ypN1>1mm (for HR-negative disease) or a CPS+EG score ≥ 3 or CPS+EG score 2 and ypN+ (for HR-positive disease) using local ER and grade assessed on core biopsies taken before start of neoadjuvant treatment.
16. Adequate surgical treatment including resection of clinically evident disease and ipsilateral axillary lymph node dissection. SNB before NACT is discouraged. Axillary dissection before NACT is not permitted. Axillary dissection, including Targeted Axillary Dissection (TAD) should be performed according to guidelines. Histologic complete resection (R0) of all invasive and in situ tumors is required.
17. Patients must have received neoadjuvant taxane-based chemotherapy for 16 weeks (anthracyclines are permitted). This period must include 6 weeks of a taxane containing neoadjuvant chemotherapy (exception: for patients with progressive disease that occurred after at least 6 weeks of taxane-containing neoadjuvant chemotherapy, a total treatment period of less than 16 weeks is also eligible).
18. No clinical evidence for locoregional or distant relapse during or after preoperative chemotherapy. Local progression during chemotherapy is not an exclusion criterion if adequate local control could be obtained. In case of local progression during neoadjuvant therapy, distant metastases must be excluded by adequate imaging (CT/MRI recommend) prior to entering the trial.
19. Immune checkpoint inhibitor / immunotherapy during (neo)adjuvant therapy is allowed until the completion of radiotherapy.
20. Inclusion criterium specific for France due to a request of the French ethics committee
21. Inclusion criterium specific for France due to a request of the French ethics committee

Exclusion criteria 17

1. Known hypersensitivity reaction to one of the compounds or substances used in this protocol.
2. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving chemotherapy.
3. History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent.
4. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
5. Known allergic reactions to irinotecan.
6. Concurrent treatment with chronic corticosteroids prior to study entry with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or equivalent corticosteroid.
7. Patients with definitive clinical or radiologic evidence of stage IV cancer (metastatic disease) are not eligible.
8. Patients with known gBRCA1/2 mutation and indicated or planned adjuvant olaparib therapy if available.
9. Patients with a history of any malignancy are ineligible with the following exceptions: patient has been disease-free for at least 5 years and is at low risk for recurrence of that malignancy; CIS of the cervix, basal cell and squamous cell carcinomas of the skin.
10. Female patients: pregnancy or lactation at the time of randomization or intention to become pregnant during the study and up to 6 months after sacituzumab govitecan and up to 6 months after treatment with capecitabine or carboplatin/cisplatin.
11. Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study, including Gilbert´s disease, Crigler-Najjar-Syndrome, known hepatitis B, hepatitis C, known HIV positivity, infection requiring intravenous antibiotic use within 1 week of enrolment or known autoimmune disease other than diabetes, stable thyroid disease, vitiligo, or other autoimmune skin disease with dermatologic manifestations only are permitted provided particular exception specified in the protocol.
12. Any condition that interferes with the safe administration of the treatment of physician’s choice in case the patient is randomized into the TPC arm.
13. Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of prior infarction on ECG, uncontrolled or poorly controlled arterial hypertension (i.e. BP >150/90 mmHg under treatment with at maximum three antihypertensive drugs), rhythm abnormalities requiring permanent treatment (excluding chronic atrial fibrillation not requiring a pacemaker), clinically significant valvular heart disease, supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker.
14. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis or active pneumonitis on chest CT scan.
15. Exclusion criterium specific for France due to a request of the French ethics committee
16. Exclusion criterium specific for France due to a request of the French ethics committee
17. Exclusion criterium specific for France due to a request of the French ethics committee

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. iDFS is defined as time from randomization until first iDFS event: local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, second non-breast primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause.

Secondary endpoints 7

1. OS is defined as the time from randomization until death from any cause.
2. DDFS is defined as the time from randomization until distant recurrence of disease, second primary invasive cancer (non-breast, excluding squamous or basal cell carcinoma of the skin), and death due to any cause.
3. iBCFS is defined as the time from randomization until first iDFS event excluding any second non-breast primary cancer.
4. LRRFI is defined as the time from randomization until any loco-regional (ipsilateral breast (invasive), chest wall, local/regional lymph nodes) recurrence of disease or any invasive contralateral breast cancer whichever occurs first. Distant recurrence, secondary malignancy and death are considered as competing risks and will be accounted for in the analysis.
5. Frequency and severity of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
6. Dose-density, dose reductions, dose delays, treatment interruptions and treatment discontinuation rates.
7. Patient reported breast cancer specific QoL as measured by FACT–B; functional assessment of cognitive function assessed by FACT-Cog; patient reported global QoL assessed by EQ-5D-5L.

Investigational products

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

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

GBG Forschungs GmbH

Sponsor organisation

GBG Forschungs GmbH

Address

Dornhofstrasse 10

City

Neu-Isenburg

Postcode

63263

Country

Germany

Scientific contact point

Organisation

GBG Forschungs GmbH

Contact name

Medicine and Research

Public contact point

Organisation

GBG Forschungs GmbH

Contact name

Medicine and Research

Third parties 9

Locations

6 EU/EEA countries · 156 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 85 files

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

Application history

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