NeoAdjuvant Therapy With Trastuzumab-deruxtecan Versus Chemotherapy+Trastuzumab+Pertuzumab in HER2+ Early Breast Cancer

Sponsor
West German Study Group
Study ID
NCT05704829
Phase
PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • HER2-positive Early Breast Cancer

Eligibility Criteria

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

Interventions

  • Trastuzumab deruxtecan — DRUG
    T-DXd i.v.
  • Standard-of-Care — DRUG
    Chemotherapy+T+P

Study Details

ADAPT-HER2-IV will address question of optimal neoadjuvant therapy in patients with less advanced -HER2+ EBC. ADAPT-HER2-IV is planned as a superiority trial to demonstrate higher pCR rates in both clinically relevant subgroups of low-intermediate risk HER2+ EBC. Moreover, it aims to demonstrate excellent survival in patients treated by T-DXd (with the use of standard chemotherapy at investigator´s decision restricted only to patients with substantial residual tumour burden after T-DXd-treatment).

Key Dates

Start date
Feb 5, 2024
Status verified
Jun 2026
Primary completion
Jun 30, 2030
Completion
Sep 30, 2030

Study Design

Enrollment
702 participants (estimated)
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT

Arms

  • Experimental: T-DXd 12 weeks: HER2+ and low-intermediate risk for recurrence
    12 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment
  • Experimental: T-DXd 18 weeks: HER2+ and intermediate-high risk for recurrence
    18 weeks T-DXd i.v. in neoadjuvant treatment; pCR dependent T-DXd for 1 year in total in postneoadjuvant treatment
  • Other: Control SoC CTx 12 weeks: HER2+ and low-intermediate risk for recurrence
    Standard-of-Care-Treatment: 12 weeks PAC+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment
  • Other: Control SoC CTx 18 weeks: HER2+ and intermediate-high risk for recurrence
    Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment
  • Experimental: T-DXd 12 weeks + SoC CTx 6 weeks
    12 weeks T-DXd i.v. follwed by 6 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment: * non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision)
  • Experimental: T-DXd 12 weeks + SoC CTx 12 weeks
    12 weeks T-DXd i.v. follwed by 12 weeks SoC chemotherapy in neoadjuvant treatment; pCR dependent postneoadjuvant treatment: * non-pCR: 14 cycles of T-DXd is strongly recommended or SoC treatment, i.e., chemotherapy and anti-HER2-treatment, including T-DM1 at investigator´s decision * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant T-DXd (12 weeks) + 12 weeks (4 cycles) of SoC chemotherapy will exceed total therapy over one year. Here, approximately 66 weeks are considered as maximum therapy (individual variations may apply)
  • Other: SoC CTx 18 weeks
    Standard-of-Care-Treatment: 18 weeks PAC/DOC+Carbo+T+P (standard-of-care) in neoadjuvant treatment; pCR dependent SOC chemotherapy +T+/-P or SOC T+/-P for 1 year in total in postneoadjuvant treatment * non-pCR (in particular ypT \>1b (5 mm) or ypN+: 14 cycles with T-DXd recommended * pCR: SoC treatment, e.g., T +/- P or T-DM1 (at investigator´s decision) Therapy for patients with non-pCR who received neoadjuvant SoC chemotherapy will exceed total therapy over one year. Here, approximately 60 weeks are considered as maximum therapy (individual variations may apply).

Primary Outcome Measure

Adverse drug reactions with CTCAE-grade 3 or higher, compared between patients treated with T-DXd neoadjuvant monotherapy for 18 weeks (part 1, cohort 2) and patients treated with SoC for 18 weeks (part 1 and 2, cohorts 2 and 3 pooled) [ Time Frame: after 18 weeks of neoadjuvant treatment ]

Central Contacts