Basket Study for Oligo-metastatic Breast Cancer (ANISE)

Basket Study for Oligo-metastatic Breast Cancer Part 1: Trastuzumab-deruxtecan for HER2-positive Oligo-metastatic Breast Cancer

The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. In the initial baskets patients with be treated with trastuzumab-deruxtecan.

Patients are treated with T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.

The proposed M22BOL trial is based on an important knowledge gap for regarding breast cancer patients with 'oligo-metastatic' disease who are usually not included in clinical trials for patients with metastatic disease since loco-regional treatments (radiation, surgery) with curative intent is not allowed in clinical trials for metastatic breast cancer. Moreover, neo-adjuvant trial protocols for early breast cancer exclude patients with distant metastases that can be treated with curative intent. This basket trial evaluates T-DXd for oligo-metastatic breast cancer with the goal to induce deep responses and subsequently long-lasting disease remissions and potentially cure.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

Detailed Description

The study will include patients with HER2-positive breast cancer and 1- 3 distant metastatic lesions, all amenable for curative intervention. Patients will be stratified by prior therapy and ER expression. Given the basket-design of this trial other baskets for oligo-metastatic breast cancer can be added, such as but not limited to other breast cancer subtypes or with other promising drugs.

Baskets for de novo oligo-metastatic disease I. ER+/HER2+ II. ER-/HER2+ Baskets for oligo-metastatic disease after prior chemo/anti-HER2 therapy for primary disease III. ER+/HER2+ IV. ER-/HER2+

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marleen Kok, MD; Phone Number: 9111 +31205129111; Email: m.kok@nki.nl
• Study Contact Backup: Name: Robbert-Jan Gielen, MD; Phone Number: 9111 +3120512

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Antoni van Leeuwenhoek
    • Principal Investigator: Marleen Kok, MD
    • Contact: Robbert-Jan Gielen, MD
    • Contact: Ingrid Mandjes, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic proof of infiltrating HER2-positive breast cancer (as determined by IHC 3+ and/or amplification by ISH)[8]
• Histologic or cytologic proof of breast cancer metastases (at least one lesion)
• Histologic determination of level of ER-expression
• Oligo-metastatic disease as determined by standard of care diagnostics. The number of total individual distant metastases is limited to five, either in one organ or in 2-5 organ systems. Clustered lymph nodes that can be irradiated with curative intent in a single field are defined as single lesion. Pleuritis carcinomatosa, miliary spread of metastases (even within one organ), or peritoneal spread of metastases rules out oligo-metastatic disease and is not allowed. Initial staging by PET-CT (whole body) and MRI of breast and brain are mandatory, as is MRI liver or spine and pelvis in case of liver or bone metastases respectively.
• In case of recurrent disease, a disease-free interval of 24 months.
• Measurable disease according to RECIST1.1
• Patients must be at least 18 years of age and be able to give written informed consent and comply with study procedures.
• World Health Organization (WHO) performance status 0 or 1

Exclusion Criteria:

• prior line of therapy for metastatic disease. Exceptions are endocrine therapy or radiation considered to be part of the curative treatment, within 3 months before enrolment
• leptomeningeal disease or central nervous metastases
• clinically relevant obstruction or compression of spinal cord, central nervous, gastro-intestinal or cardiovascular system, that cannot be alleviated before start of treatment.
• other malignancy, unless treated with curative intention and a long-term survival probability of >95%, including in-situ or pre-malignant lesions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab-deruxtecan; 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.	Drug: Trastuzumab deruxtecan; T-DXd 5.4mg/kg on a three weekly (21 day) basis, with the goal of 16 cycles leading to a treatment period of year, including local treatment. The first 8 cycles of T-DXd are administered neo-adjuvant, and 8 cycles adjuvant, after completion of local treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete radiologic response	Number of patients to achieve radiologic response as defined by RECIST 11 with clearnace of ctDNA	up to one year after start treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients free of progression	as defined by RECIST	assessed up to 10 years
Overall Survival	time from start treatment to death from any cause	assessed up to 10 years
Number of patients with pathological complete response	after resection of primary tumor and/or metastatic lesions after neo-adjuvant treatment	assessed immediately after surgery
Number of patients with metabolic response	as measured with PDG-PET	assessed up to 12 months
Number of patients with metabolic response	as measured by clearance of ctDNA	assessed up to 10 years
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	determined accoriding to CTCAE v5.0 or Clavien-Dindo (in case of surgical resection)	assessed up to 30 days after last treatment

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: AstraZeneca; Daiichi Sankyo
• Investigators: Principal Investigator: Marleen Kok, MD, Antoni van Leeuwenhoek

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2034

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: August 7, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Oligometastatic disease (max 3 lesions)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; trastuzumab deruxtecan
• Other Study ID Numbers: M22BOL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: to de decided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No