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

Sponsor
West German Study Group
Study ID
NCT07178730
Phase
PHASE3
Status
Not Yet Recruiting

Notify me when recruiting opens

Save your spot on the interest list for this study. We'll keep your details with this study so our team can follow up when recruiting opens.

Not yet recruiting

Add your contact details and location so we can keep your interest tied to this study.

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Sacituzumab govitecan — DRUG
    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.
  • Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] — DRUG
    Pembrolizumab 200 mg will be administered as a 30-minute i.v. infusion every 3 weeks.
  • SoC Chemotherapy — DRUG
    Standard of care chemotherapy as per common treatment guidelines and recommendations

Study Details

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.

Key Dates

Start date
Jun 30, 2026
Status verified
Jun 2026
Primary completion
Mar 31, 2033
Completion
Mar 31, 2033

Study Design

Enrollment
765 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Other: Cohort I (non-randomized)
    Cohort I will include patients with clinical stage II disease at baseline who have a cCR after up to 12 weeks of NACT with CARBO/PAC and PEM. After surgery, patients with a pCR (ypT0/is, ypN0) will not receive further chemotherapy (CTx) but continue on SoC treatment according to current valid treatment guidelines for breast cancer at investigator´s discretion. Patients with residual disease should be considered for postoperative SoC treatment, which may include further CTx (e.g., AC/EC x 4, q2w or q3w or Capecitabine) plus PEM or Olaparib (in patients with gBRCA mutations) according to current valid treatment guidelines for breast cancer and per investigator´s discretion.
  • Experimental: Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM)
    neoadjuvant SG+PEM (4 cycles), followed by surgery and pCR-dependent post-neoadjuvant SoC treatment according to current valid treatment guidelines for breast cancer and per investigator´s discretion.
  • Active Comparator: Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM)
    SoC, e.g., AC x 4 + PEM or EC x 4 + PEM, followed by surgery and pCR-dependent post-neoadjuvant SoC treatment, e.g., AC x 4 \* PEM or EC x 4 + PEM, or Capecitabine + PEM or Olaparib (in patients with gBRCA mutations), according to current valid treatment guidelines for breast cancer and per investigator´s discretion.

Primary Outcome Measure

Cohort I: 3-year event-free survival (EFS) [ Time Frame: EFS 3 years ]

Central Contacts

Related Studies