Margetuximab Plus Tucatinib and Capecitabine in HER2-positive Metastatic Breast Cancer

NCT05227131 | Withdrawn Phase 2

• 2 other identifiers: MEDOPP4472021-006387-24
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of margetuximab in combination with tucatinib and capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.

Conditions

Metastatic Breast Cancer; Advanced Breast Cancer; HER2-positive Breast Cancer

Keywords

Metastatic Breast Cancer; Breast Cancer; HER2-positive; Tucatinib; Margetuximab; Capecitabine

Outcome Measures

Primary Outcomes (1)

• Efficacy (Overall Response Rate (ORR))

  The primary efficacy endpoint is the overall response rate (ORR), which is defined as the number of patients with complete response (CR) and partial response (PR) divided by the number of patients in the analysis set. CR and PR must be radiologically confirmed at the next tumor assessment after initial observation of response, as determined locally by the Investigator through the use of RECIST v.1.1 criteria.

  29 months

Secondary Outcomes (9)

• Efficacy (unconfirmed ORR)

  29 months

• Efficacy (CBR)

  29 months

• Efficacy (PFS)

  29 months

• Efficacy (TTP)

  29 months

• Efficacy (TTR)

  29 months

Study Arms (1)

Margetuximab + Tucatinib + Capecitabine

EXPERIMENTAL

All eligible patients will receive the combination of margetuximab 15 mg/kg by intravenous infusion on Day 1 of each cycle (no loading dose is required), capecitabine at 1000 mg per square meter of body-surface area orally twice daily on days 1 to 14 of each 21-day cycle, and tucatinib 300 mg orally twice daily (every 12 hours) continuously in 21-day cycles.

Drug: Margetuximab; Drug: Tucatinib; Drug: Capecitabine

Interventions

Margetuximab DRUG

Margetuximab (15 mg/kg) will be administrated by intravenous infusion on Day 1 of each cycle.

Margetuximab + Tucatinib + Capecitabine

Tucatinib DRUG

Tucatinib (300 mg) will be administrated orally twice daily (every 12 hours) continuously in 21-day cycles.

Margetuximab + Tucatinib + Capecitabine

Capecitabine DRUG

Capecitabine (1000 mg per square meter of body-surface area) will be administrated orally twice daily on days 1 to 14 of each 21-day cycle

Margetuximab + Tucatinib + Capecitabine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form (ICF) prior to participation in any study-related activities.
• Male or female patients ≥ 18 years of age at the time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy of ≥ 16 weeks.
• Histologically confirmed HER2-positive breast cancer according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines 2018 based on local testing on the most recent analyzed biopsy.
• Note: Central confirmation of HER2-positive status is not required for study entry. However, tissue blocks, or slides, must be submitted to confirm HER2 positivity by a Sponsor-designated central laboratory retrospectively.
• Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.
• Disease progression after last systemic therapy documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI).
• Note: Exclusive tumor marker elevation will not be considered sufficient for diagnosis of disease progression.
• Centrally confirmed low affinity CD16A germline genotype (F/F or F/V).
• Measurable disease as per RECIST v.1.1 criteria.
• Have received treatment with at least one, and no more than three, HER2-targeting treatment regimens overall for unresectable locally advanced or MBC. Earlier adjuvant or neoadjuvant HER2-targeted therapy for more limited disease will be considered as one of the required prior regimens if the development of unresectable locally advanced or metastatic disease occurred within a 6-month period of time after completion of anti-HER2 therapy. In any case, patients must have received prior treatment with any anti-HER2 antibody drug conjugate (ADC) in the (neo)adjuvant or metastatic setting.
• Note: Eligible patients must have progressed on or following, the most recent line of therapy. Dose interruptions, delays, pauses during previous therapy, or changes in therapy to manage toxicity will not constitute a new line of therapy provided disease progression did not occur.
• Willingness and ability to provide a tumor biopsy at study entry and after progression from either metastatic or primary tissues in order to perform exploratory studies. If not feasible, patient eligibility should be evaluated by a Sponsor's qualified designee.
• Note: Subjects for whom tumor biopsy cannot be obtained (e.g., inaccessible tumor or subject safety concern) may submit archival pathological material from either metastatic or primary sites, but the most recent tumor biopsy from the patient should be obtained when available at both timepoints.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Inability to comply with study and follow-up procedures.
• Prior exposure to margetuximab, capecitabine or other fluoropyrimidine \[e.g., 5-fluorouracil\] or any HER2 tyrosine kinase inhibitor (TKI) tucatinib, and/or dual HER2/epidermal growth factor receptor (EGFR) TKIs (lapatinib, neratinib, afatinib, etc.) except for the following conditions:
• Lapatinib at least 12 months prior to starting study treatment (except in cases where lapatinib was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity);
• Patients who have received capecitabine for adjuvant or neoadjuvant treatment at least 12 months prior to starting study treatment are eligible (except in cases where capecitabine was given for ≤ 21 days and was discontinued for reasons other than disease progression or severe toxicity).
• Presence of carcinomatous meningitis or leptomeningeal disease.
• Extracranial radiation therapy within 14 days (seven days for limited-field palliative radiotherapy) prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to grade ≤ 1.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 14 days from the start of study treatment (28 days for brain surgical resection), or patients who have not recovered from the side effects of any major surgery.
• Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.
• Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drugs.
• History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation.
• Treatment with systemic steroids (e.g., ≥ 10 mg prednisone per day or equivalent) or other immunosuppressive drugs within 14 days prior to study treatment initiation. Standard premedication for margetuximab and topical applications of steroids are allowed.
• Current known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
• Active uncontrolled infection at the time of enrollment.
• Congenital long QT syndrome or screening QT interval corrected using Fridericia's formula (QTcF) \> 480 milliseconds.

Sponsors & Collaborators

• MedSIR: lead
• MacroGenics: collaborator
• Seagen Inc.: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

margetuximab; tucatinib; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Javier Cortés, MD, PhD

  MedSIR

  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

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: February 7, 2022
• Study Start: May 15, 2022
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: July 11, 2022

Record last verified: 2022-07