NCT04595565

Sacituzumab Govitecan in Primary HER2-negative Breast Cancer

Phase III Postneoadjuvant Study Evaluating Sacituzumab Govitecan, an Antibody Drug Conjugate in Primary HER2-negative Breast Cancer Patients With High Relapse Risk After Standard Neoadjuvant Treatment - SASCIA

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,332 (estimated)
• Sponsor: GBG Forschungs GmbH · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Phase III, prospective, multi-center, randomized, open label, parallel group, study in patients with HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy with 1:1 allocation to: * Arm A: Sacituzumab govitecan (days 1, 8 q3w for eight cycles); * Arm B: treatment of physician´s choice (TPC, defined as capecitabine or platinum-based chemotherapy for eight cycles or observation. Treatment in either arm will be given for eight cycles. In patients with HR-positive breast cancer, endocrine-based therapy, which includes the use of CDK4/6 inhibitors, will be administered according to local guidelines. The start of endocrine therapy will be at the discretion of the investigator; however, it will be encouraged to start after surgery/radiotherapy in patients without additional cytotoxic agents. Adjuvant pembrolizumab can be given until the completion of radiotherapy before randomization. Within the study the use of pembrolizumab in patients with TNBC who received pembrolizumab as neoadjuvant therapy is allowed as monotherapy in the TPC arm, according to the approval of pembrolizumab in this setting.

Detailed description

Neoadjuvant chemotherapy (NACT) allows monitoring of tumor response to treatment and a pathological complete response (pCR) is associated with superior survival. This association is strongest in the most aggressive subtype, i.e. in patients with triple-negative breast cancer (TNBC). Patients with TNBC not achieving a pCR have a 5-year event free survival rate of about 50%. The association between pCR and prognosis is less pronounced in HR-positive/HER2-negative patients. However, the CPS+EG scoring system for prognosis after neoadjuvant chemotherapy, taking into account clinical stage, post treatment pathological stage, estrogen receptor status and grade, leads to an improved estimate of prognosis allowing to select patients at high risk of relapse for post-neoadjuvant therapy. Patients with TNBC not achieving a pCR as well as those with HR-positive/HER2-negative tumors and a CPS+EG score of 3 or 2/ypN+ are at high risk of relapse, warranting additional experimental therapies after NACT. There is proof of concept, that post-neoadjuvant therapy can significantly improve survival. First data was provided by the CREATE X trial, randomizing patients with residual tumor after neoadjuvant chemotherapy to either capecitabine or observation. CREATE X included HER2-negative patients and demonstrated a significant improvement in disease-free survival (DFS) and overall survival (OS) in the overall population, which was confined to the TNBC subgroup. Recently, the randomized post-neoadjuvant phase III KATHERINE study demonstrated an improved invasive disease-free survival in HER2-positive patients without pCR after trastuzumab +/- pertuzumab treated postoperatively with T-DM1, an antibody-drug-conjugate compared to trastuzumab. Sacituzumab govitecan has demonstrated unprecedented activity in heavily pretreated patients with metastatic triple-negative and HR-positive/HER2-negative breast cancer, even after prior immune-checkpoint inhibitors or CDK4/6 and mTOR inhibitors. Based on the results of the phase I/II study, sacituzumab govitecan was granted a breakthrough therapy designation for the treatment of patients with advanced or metastatic TNBC who have received at least two previous lines of treatment for metastatic disease. The efficacy of sacituzumab govitecan in advanced TNBC was confirmed in the phase III ASCENT trial. Based on this study, sacituzumab govitecan received regular approval. Additionally, the TROPiCS-02 study showed an improvement in progression-free survival and OS over single-agent chemotherapy and a manageable safety profile in patients with heavily pre-treated HR-positive/HER2-negative endocrine-resistant, unresectable locally advanced or metastatic BC.

Conditions

• HER2-negative Breast Cancer
• Triple Negative Breast Cancer

Interventions

Type	Name	Description
DRUG	Capecitabine	2000 mg/m² day 1-14 q21 day cycle for eight cycles
DRUG	Carboplatin	AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles
DRUG	Cisplatin	25mg/m3 weekly or 75 mg/m3 q3w
DRUG	Sacituzumab govitecan	10 mg/kg body weight on days 1, 8 q3w

Timeline

• Start date: 2020-10-28
• Primary completion: 2027-03-30
• Completion: 2029-03-30
• First posted: 2020-10-20
• Last updated: 2025-11-25

Locations

163 sites across 7 countries: Austria, Belgium, France, Germany, Ireland, Spain, Switzerland