Study of DS-8201a, an Antibody Drug Conjugate for Advanced Breast Cancer Patients, With Biomarkers Analysis

NCT04132960 | Completed Phase 2 DMC

• 2 other identifiers: UC-0105/18152018-004868-57
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 15

Brief Summary

Multicenter, open-label phase II trial assessing the efficacy of DS-8201a monotherapy in patients with metastatic breast cancer.

Conditions

Breast Tumors

Keywords

DS-8201a; ADC; HER2; metastatic breast cancer

Outcome Measures

Primary Outcomes (1)

• Antitumor activity of DS-8201a in the 3 cohorts of patients

  The primary endpoint is antitumor activity of DS-8201a carried out by the determination of the confirmed best objective response (BOR) rate in each cohort. The BOR is defined as the presence of a confirmed partial or complete response observed on treatment, as assessed by investigators.

  12 months

Study Arms (1)

HER2 status

EXPERIMENTAL

Three cohorts of advanced breast cancer patients: * Cohort 1: HER2 over-expressing (HER2 IHC3+ or HER2 IHC2+/ISH+) * Cohort 2: HER2 low-expressing (IHC1+ or IHC2+/ISH-) * Cohort 3: HER2 non-expressing (IHC0+)

Drug: DS-8201a

Interventions

DS-8201a DRUG

Anti-HER2-antibody drug conjugate (ADC)

HER2 status

Eligibility Criteria

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

You may qualify if:

• Patient must have signed a written informed consent form prior to any study specific procedures. When the patient is physically unable to give his/her written consent, a trusted person of his/her choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent.
• Female or male subjects aged ≥18 years.
• Patient with histologically-confirmed diagnosis of invasive breast cancer. Tumors can be either HER2 immunohistochemistry (IHC)3+/in situ hybridization (ISH) positive or IHC2+/ISH positive or IHC2+/ISH negative or IHC1+ or IHC0+, of most recent tumor tissue sample available.
• Patient with a documented radiologic metastatic progression.
• Patient considered by the investigator as not amenable to any other validated therapeutic option, after at least 1 line of chemotherapy in metastatic setting. Patient must have been previously treated with anthracyclines and taxanes (in (neo-)adjuvant and/or metastatic setting). Additionally:
• Patient with HER2 over-expressing (IHC3+ and IHC2+/ISH+) tumor must have been treated and have progressed on trastuzumab and on TDM-1. Prior treatment with pertuzumab is not required.
• Patient with HER2 negative (IHC0, 1+, and 2+/ISH-) and hormone receptor positive (estrogen receptor (ER)+ and/or progesterone receptor (PR)+) tumor must be resistant to endocrine therapy and CDK4/6 inhibitors, and must have been treated with capecitabine.
• Non-bone metastatic site easily accessible to biopsy.
• Presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
• Patient with world health organization (WHO) performance status ≤1.
• Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and hemoglobin ≥9 g/dL (transfusion is not allowed within 1 week prior to baseline assessment).
• Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range if no liver metastases or \<3 x ULN in the presence of documented Gilbert's Syndrome or liver metastases. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤3 × ULN (AST and ALT≤ 5 ULN when documented liver metastasis).
• Adequate blood clotting function: International Normalized Ratio (INR)/Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) ≤1.5 x ULN.
• Adequate renal function: estimated creatinine clearance ≥30 mL/min according to the Cockcroft-Gault formula or serum creatinine ≤1.5 x ULN.
• Male and female subjects of reproductive/childbearing potential must agree to use of a highly effective contraception for subjects throughout the study and for at least 4.5 months after last study treatment administration if the risk of conception exists.

You may not qualify if:

• Patient with a breast cancer amenable for resection or radiation therapy with curative intent.
• Patient has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
• Patient with bone metastatic disease only.
• Patient with multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.
• Persistent unresolved toxicities with grade ≥2 (except alopecia and renal function). Subject with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor (eg, Grade 2 chemotherapy-induced neuropathy).
• Patient using drugs that could have pharmacokinetics interaction with investigational drugs. Concomitant use of strong CYP3A4 inhibitors or OATP 1B inhibitors should be avoided. If concomitant use of strong CYP3A4 or OATP 1B inhibitors is unavoidable, consider delaying DS-8201a treatment until the inhibitors have cleared from the circulation (approximately 3 elimination half-lives of the inhibitors) when possible. If a strong CYP3A4 inhibitor or an OATP 1B inhibitor is co-administered and DS-8201a treatment cannot be delayed, patients should be closely monitored for adverse reactions.
• Patients with a concomitant use of chronic systemic (intravenous or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra articular steroid injections are permitted in this study.) Subjects with bronchopulmonary disorders who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study.
• Patient with history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Patient with clinically significant corneal disease in the opinion of the Investigator.
• Known prior severe hypersensitivity to investigational product or any component in its formulation, including known severe hypersensitivity reactions to study drug (National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≥3).
• Patient has a history of severe hypersensitivity reactions to other monoclonal antibodies.
• Patients previously treated with topoisomerase 1 inhibitor.
• Patient has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation of the subject or evaluation of the clinical study in the opinion of the Investigator.
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome.
• Known active hepatitis B virus or hepatitis C virus infection at screening.

Sponsors & Collaborators

• UNICANCER: lead
• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: collaborator

Study Sites (15)

Institut Bergonié

Bordeaux, France

Location

Centre François Baclesse

Caen, France

Location

Centre Jean Perrin

Clermont-Ferrand, France

Location

Centre Hospitalier Universitaire Dupuytren

Limoges, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Institut Jean Godinot

Reims, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institut Curie - Hôpital Huguenin

Saint-Cloud, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Institut de Cancérologie Strasbourg Europe (ICANS)

Strasbourg, France

Location

Institut Claudius Regaud

Toulouse, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Mosele F, Deluche E, Lusque A, Le Bescond L, Filleron T, Pradat Y, Ducoulombier A, Pistilli B, Bachelot T, Viret F, Levy C, Signolle N, Alfaro A, Tran DTN, Garberis IJ, Talbot H, Christodoulidis S, Vakalopoulou M, Droin N, Stourm A, Kobayashi M, Kakegawa T, Lacroix L, Saulnier P, Job B, Deloger M, Jimenez M, Mahier C, Baris V, Laplante P, Kannouche P, Marty V, Lacroix-Triki M, Dieras V, Andre F. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med. 2023 Aug;29(8):2110-2120. doi: 10.1038/s41591-023-02478-2. Epub 2023 Jul 24.

  PMID: 37488289 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

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

Study Officials

• Véronique DIERAS

  Centre Eugène Marquis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The main objective is to evaluate the anti-tumor activity of DS-8201a in three cohorts of advanced breast cancer patients: * Cohort 1: HER2 over-expressing (HER2 IHC3+ or HER2 IHC2+/ISH+) * Cohort 2: HER2 low-expressing (IHC1+ or IHC2+/ISH-) * Cohort 3: HER2 non-expressing (IHC0+)

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 21, 2019
• Study Start: October 21, 2019
• Primary Completion: October 29, 2021
• Study Completion: December 26, 2024
• Last Updated: June 12, 2025

Record last verified: 2025-06

Locations

FR (15)