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

NCT07178730 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: WSG-AM15 (ADAPT-TN-IV)2024-516734-35-00
• Study Type: interventional
• Target: 765
• Locations: 0 countries
• Sites: N/A

Brief 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. 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. 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.

Conditions

Breast Cancer; Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Cohort I: 3-year event-free survival (EFS)

  EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy (same definition as iDFS) according to STEEP 2.0 criteria \[103\]

  EFS 3 years

• Cohort II: superiority of neoadjuvant treatment with SG+PEM vs. SoC with regards to event-free survival (EFS)

  EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy or local progress precluding surgery in neoadjuvant treated patients

  EFS 3 years

• Cohort II: superiority of neoadjuvant treatment with SG+PEM vs. SoC with regards to pathological complete response (pCR) rates

  pCR defined as no invasive disease in breast and lymph nodes (ypT0/is, ypN0) in patients of both arms

  EFS 3 years

Secondary Outcomes (11)

• clinical response after 12 weeks of neoadjuvant chemotherapy treatment (NACT)

  12 weeks NACT

• distant disease-free survival (dDFS)

  3 years

• relapse-free survival (RFS)

  3 years

• locoregional relapse-free survival (LRFS)

  3 years

• overall survival (OS)

  3 years

Study Arms (3)

Cohort I (non-randomized)

OTHER

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.

Drug: SoC Chemotherapy

Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM)

EXPERIMENTAL

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.

Drug: Sacituzumab govitecan; Drug: Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]

Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM)

ACTIVE COMPARATOR

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.

Drug: Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA]; Drug: SoC Chemotherapy

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.

Also known as: Trodelvy

Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM)

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.

Also known as: Keytruda

Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM); Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM)

SoC Chemotherapy DRUG

Standard of care chemotherapy as per common treatment guidelines and recommendations

Also known as: diverse

Cohort I (non-randomized); Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Minimal eligibility criteria to be met for registration in the clinical trial:
• TNBC: ER = 0%, PR = 0%, and HER2- (i.e., immunohistochemistry \[IHC\] with DAKO score ≤ 1 or fluorescence in situ hybridization \[FISH\]-negative)
• or TNBC-like: ER ≤ 10% positive cells in IHC, PR \< 10% positive cells in IHC, and HER2- (i.e., IHC with DAKO score ≤ 1 or FISH negative)
• All patients, independent from gender
• ≥18 years at diagnosis
• Histologically confirmed unilateral, primary invasive carcinoma of the breast Note: bilateral, multicentric, or multifocal carcinoma may be included, if there is a clear target (primary) lesion, that is subject to treatment decisions and solely evaluated and documented for study purposes. Histological confirmation of all lesions as TNBC is mandatory.
• Clinical stage II-III at baseline
• No clinical evidence for distant metastasis (M0)
• Cognitive and language skills to complete quality of life (QoL) questionnaires
• Additional eligibility criteria to be met for assignment to cohort I or II:
• Completed 9-12 weeks of NACT with CARBO + PEM or PAC q1w + PEM q3w with the last dose of NACT given less than 2 weeks ago. Patients may also be considered if their NACT treatment was switched to nab-PAC due to intolerance to PAC.
• Patients with progressive disease during taxane-CARBO treatment are allowed to participate in cohort II after consultation with sponsor, provided that at least 6-9 weeks of NACT with taxane-CARBO q1w and PEM q3w have been administered
• Patients experiencing toxicities due to PEM, in case of contraindications or other medical reasons against PEM administration (with or without permanent discontinuation of PEM) can nevertheless be included, even if PEM will not be administered anymore. The number of patients starting the study without PEM is limited to 10%.
• Tumour block available for central pathology review
• Performance Status ECOG ≤ 1 or Karnofsky Index ≥ 80%

You may not qualify if:

• Known hypersensitivity to the compounds or incorporated substances of the IMPs
• Prior malignancy with a disease-free survival of \< 5 years, except curatively treated basalioma of the skin or pTis of the cervix uteri
• Any history of invasive breast cancer
• Previous or concurrent treatment with cytotoxic agents for any non-oncological reason unless clarified with sponsor
• Concurrent treatment with other experimental drugs
• Participation in another interventional clinical trial with or without any investigational, not marketed drug within 30 days or 5 half-lives of the respective drug, whichever is longer, prior to study entry. In case of other interventional trial contact Sponsor.
• Concurrent pregnancy: patients of childbearing potential or potentially childbearing partners of male patients must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
• Breast feeding woman
• Reasons indicating risk of poor compliance
• Patients not able to consent
• Known polyneuropathy ≥ grade 2
• Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including recovery from major surgery, autoimmune disease, known psychiatric/substance abuse disorders, acute cystitis, ischuria, and chronic kidney disease
• Uncontrolled infection requiring i.v. antibiotics, antivirals, or antifungals
• History of pneumonitis haemolytic anaemia, myocarditis, sclerosing cholangitis and exocrine pancreatic insufficiency, medical history of allogenic stem cell transplants, or solid organ transplant
• Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection. Patients should be tested for HIV prior to randomization if required by local regulations or ethics committee. Patients who test positive for HIV-antibody are excluded.

Sponsors & Collaborators

• Gilead Sciences: collaborator
• West German Study Group: lead

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

sacituzumab govitecan; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Peter Schmid, PHD Dr

  Westdeutsche Studiengruppe GmbH

  PRINCIPAL INVESTIGATOR

• Nadia Harbeck, Prof Dr

  Breast Centre, Dept. Obstetrics & Gynaecology and CCC Munich LMU University Hospital Munich Germany

  PRINCIPAL INVESTIGATOR

• Oleg Gluz, Prof Dr

  Breast Centre, Evang. Bethesda-Hospital Moenchengladbach Germany

  PRINCIPAL INVESTIGATOR

• Sherko Kuemmel, Prof Dr

  Breast Centre, Kliniken Essen Mitte Essen Germany

  PRINCIPAL INVESTIGATOR

• Monika Graeser, PD Dr

  Breast Centre, Marien-Hospital Witten Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anja Braschoß

CONTACT

017682119153; regulatory@wsg-online.com

Marina Mangold, Dr

CONTACT

02161566230; marina.mangold@wsg-online.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicentre, interventional, prospective, two-cohort, two-arm, partially randomized, open-label, controlled neoadjuvant, phase III trial evaluating the efficacy and safety of SG+PEM vs. SoC in stage II-III early TNBC.

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 17, 2025
• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): March 31, 2033
• Study Completion (Estimated): March 31, 2033
• Last Updated: May 6, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share