NCT07178730

NeoAdjuvant Therapy Comparing Sacituzumab Govitecan+Pembrolizumab vs. SoC Chemotherapy in Clinical Stage II-III, Triple-negative Early Breast Cancer

NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Sacituzumab Govitecan+Pembrolizumab vs. SoC Chemotherapy in Clinical Stage II-III, Triple-negative Early Breast Cancer

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 765 (estimated)
• Sponsor: West German Study Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

TNBC is a heterogeneous disease with distinct pathological, genetic, and clinical features among subtypes. Treatment results for high-risk primary TNBC remain poor compared to other breast cancer subtypes. Preoperative chemotherapy is the standard of care for patients with stage II or III primary TNBC. Multiple lines of clinical evidence demonstrate that TNBC patients who achieve a pCR to NACT, (ypT0/is ypN0), have an excellent long-term prognosis. A meta-analysis of individual patient data confirmed a strong association of pCR after NACT with improved long-term event-free survival (EFS, hazard ratio \[HR\] 0.24) and overall survival (OS, HR 0.16) benefit. Taxane- and anthracycline-based neoadjuvant regimens generally result in pCR rates between 25-50% \[REFs\], whereas the addition of platinum increases pCR rates to approximately 50-55%. The KEYNOTE-522 trial has demonstrated that the addition of the immune-checkpoint inhibitor PEM to anthracycline- (AC), taxane- and platinum-based NACT resulted in a significant increase in pCR rates to nearly 65%, associated with a significant reduction of recurrences (EFS, HR 0.65 at 5 years) and improvement of OS (HR 0.66). Based on these results, the KEYNOTE-522 regimen has been approved by the FDA and EMA and has become the standard of care for patients with stage II or III TNBC. Despite this significant progress, two major questions remain unresolved which will be investigated in the ADAPT-TN-IV trial: 1. Do all patients require the full 6 months of NACT as per KEYNOTE-522 or is there a subgroup of patients who are sufficiently treated with 12 weeks of NACT plus PEM? 2. Can incorporation of ADCs into the KEYNOTE-522 regimen improve response and outcomes in patients without an optimal early response? The outcome of patients with residual disease after 24 weeks of NACT and PEM remains suboptimal and there is an urgent need for more effective strategies. ADCs such as SG have demonstrated superior efficacy compared to standard chemotherapy in metastatic TNBC, resulting in substantially higher response rates and improved progression-free (PFS) and OS. Combination studies of ADCs and immunotherapy in metastatic TNBC have demonstrated significant activity, suggesting possible synergistic activity It is therefore a logical next step to investigate, whether the incorporation of SG in the NACT regimen can improve pCR rates and EFS results in patients who have residual clinical disease after 12 weeks of NACT with CARBO/PAC + PEM.

Detailed description

The trial will have two cohorts. COHORT I - SoC DE-ESCALATION Cohort I will include patients with clinical stage II TNBC who have achieved a cCR to 12 weeks of NACT with CARBO/ PAC, and PEM. The trial will evaluate whether these patients can be safely spared from further chemotherapy (CTx) and directly proceed to surgery. If it is unclear whether patients have a cCR, a tumour biopsy (by ultrasound or mammography/MRI-guided) is required to confirm that there is no evidence of residual invasive disease. After surgery, patients with a pCR (ypT0/is, ypN0) will not receive further chemotherapy, but continue otherwise on SoC treatment. Patients with residual disease should be considered for postoperative SoC treatment, which might include further CTx (e.g., AC or AC x4) plus PEM or OLA (in patients with gBRCA mutations). COHORT II - ADC-INTENSIFICATION (STUDY TREATMENT) vs. SoC Cohort II will include all clinical stage III-patients and stage II patients without a cCR after 12 weeks of NACT with CARBO/ PAC and PEM. If it is unclear whether patients have a cCR, a tumour biopsy (by ultrasound or mammography/MRI-guided) is required to confirm that there is no evidence of residual invasive disease. These patients will be randomized 1:1 to further neoadjuvant treatment in either * Arm 1: neoadjuvant SG+PEM, followed by surgery and pCR-dependent post-neoadjuvant SoC treatment or * Arm 2: SoC CTx+SoC, followed by surgery and pCR-dependent post-neoadjuvant SoC treatment

Conditions

• Breast Cancer
• Triple-negative Breast Cancer

Interventions

Type	Name	Description
DRUG	Sacituzumab govitecan	SG is administered at 10 mg/kg as an intravenous (i.v.) infusion on Days 1 and 8 of a 21-day cycle. The dose of SG will be calculated based on actual weight at randomization (using weight obtained either at enrolment or on Cycle 1 Day 1) and remains constant throughout the study, unless there is a \> 10% change in body weight from baseline. Modifications to the study drug doses administered should be made for a \> 10% change in body weight from baseline and according to local and regional prescribing standards. Dose modifications for changes in body weight \< 10% may be made according to local institutional guidelines. SG is administered via i.v. infusion as described below with additional information available in the current version of the SmPC.
DRUG	Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]	Pembrolizumab 200 mg will be administered as a 30-minute i.v. infusion every 3 weeks.
DRUG	SoC Chemotherapy	Standard of care chemotherapy as per common treatment guidelines and recommendations

Timeline

• Start date: 2026-01-31
• Primary completion: 2033-03-31
• Completion: 2033-03-31
• First posted: 2025-09-17
• Last updated: 2025-09-17