Tucatinib Together With Pembrolizumab and Trastuzumab

NCT04789096 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: BCT 2102
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 15

Brief Summary

Women or men with HER2-positive, metastatic breast cancer, who have progressed on previous treatment, will receive tucatinib in combination with pembrolizumab and trastuzumab (PD-L1 positive).

Conditions

Breast Cancer; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in the PD-L1 positive cohort

  Defined as complete response (CR) or partial response (PR) assessed as per RECIST 1.1

  Through to study completion, an average of 24 months

Secondary Outcomes (8)

• Objective response rate (ORR) in the PD-L1 negative/unknown cohort

  Through to study completion, an average of 24 months

• Progression free survival (PFS) in each PD-L1 cohort

  From the time of registration until documented disease progression by RECIST 1.1 or death due to any cause (whichever occurs first), assessed up to 24 months

• Duration of response (DoR) in each PD-L1 cohort

  From the time of registration to first documentation of progressive disease or death, assessed up to 24 months

• Clinical benefit rate (CBR) in each PD-L1 cohort

  From time of registration to CR or PR, assessed up to 24 months

• Overall survival (OS) in each PD-L1 cohort

  From time of registration until death from any cause, assessed at 24 months

Other Outcomes (8)

• CNS progression in each PD-L1 cohort in participants with or without evidence of brain metastases at baseline by local image review.

  From the start of study treatment to the date of first CNS progression, assessed at 24 months

• Extra-cranial PFS in each PD-L1 cohort

  Until documented disease progression, assessed at 24 months

• PFS in participants with or without evidence of brain metastases at baseline in each PD-L1 cohort

  Until documented disease progression or death due to any cause, assessed at 24 months

Study Arms (1)

TUGETHER Treatment

EXPERIMENTAL

Participants will receive: * Tucatinib (oral) at a dose of 300 mg BD on day 1-21 of each 21-day cycle * Pembrolizumab will be administered at a dose of 200 mg IV on day 1 of each 21 day cycle * Trastuzumab will be given as a loading dose of 8 mg/kg IV (if loading required, otherwise 6 mg/kg) on day 1 followed by 6 mg/kg on day 1 of each 21 day cycle. Participants registered to PD-L1 negative/unknown cohort prior to Protocol Amendment 2 received Capecitabine 1000 mg/m\^2 day 1-14 of each 21 day cycle.

Drug: Tucatinib; Drug: Pembrolizumab; Drug: Trastuzumab; Drug: Capecitabine

Interventions

Tucatinib DRUG

Oral tablet

Also known as: Tukysa

TUGETHER Treatment

Pembrolizumab DRUG

Intravenous

Also known as: Keytruda

TUGETHER Treatment

Trastuzumab DRUG

Intravenous

Also known as: Herceptin

TUGETHER Treatment

Capecitabine DRUG

Oral tablet

Also known as: Xeloda

TUGETHER Treatment

Eligibility Criteria

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

You may qualify if:

• Has provided written, informed consent to participate in the study.
• Female or male, age ≥ 18 years.
• Local histologically confirmed HER2-positive unresectable loco-regional or metastatic breast cancer. HER2-positive according to ASCO CAP 2018 guidelines defined as:
• ISH testing with ERBB2-amplification as demonstrated by ratio ERBB2/centromeres ≥ 2.0 or mean gene copy number ≥ 6 OR
• + staining by IHC.
• FFPE tumour samples (preferably two blocks) available from newly obtained biopsies of advanced disease for assessment of PD-L1, TILs status and correlative research. If new biopsies are not obtainable then primary/metastatic archival biopsies (preferably two samples) from within 12 months of registration may be provided.For those participants whose tissue is unavailable despite best efforts (e.g. inadequate sample or primary tumour lost/discarded), please discuss with BCT and the Study Chairs.
• Must have previously received taxane, trastuzumab, pertuzumab and an antibody-drug conjugate (ADC) in either the (neo) adjuvant or advanced disease setting. Any number of prior lines of anti-HER2 therapy is acceptable.
• Have progression of unresectable locally advanced or metastatic breast cancer during or after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy.
• Have a life expectancy of at least 6 months, in the opinion of the investigator.
• Women of childbearing potential (WOCBP) and men with partners of childbearing potential must agree to use a highly effective contraception from the signing of informed consent until 7 months after the last dose of protocol treatment.
• Note: Use of oral, injectable or implant hormonal contraceptives or medicated IUD must stop before registration.
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during both the treatment and follow-up phases.
• Confirmed submission to the central laboratory of tumour tissue for PD-L1 status to determine cohort . For those participants whose tissue is unavailable for testing, individual cases must be discussed with BCT and the Study Chairs. Note: the first 10 participants will be reviewed for PD-L1 positivity rates
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have measurable disease assessable by RECIST v1.1.

You may not qualify if:

• Previously treated with:
• Lapatinib within 12 months of registration OR
• Neratinib or afatinib within 12 months of registration, unless ceased due to toxicity and not progression.
• Prior anti-PD-1, anti-PD-L1/L2 or anti-CTLA4 therapy, including, but not limited to: pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, ipilimumab, tremelimumab.
• Previous severe hypersensitivity reaction to treatment with TKI or monoclonal antibody that is biologically similar to the study treatments.
• Known leptomeningeal disease as documented/determined by the investigator.
• Have poorly controlled (\> 1/week) generalised or complex partial seizures, or manifest neurologic progression due to brain metastases despite CNS-directed therapy.
• History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥ 3), angina, myocardial infarction or ventricular arrhythmia. Have known myocardial infarction or unstable angina within 6 months before registration.
• Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• History of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible
• Stable diabetes mellitus are eligible
• Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible provided ALL the following conditions are met:
• i) Rash must cover \< 10% of body surface area ii) Disease is well controlled at baseline and requires only low-potency topical corticosteroids iii) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
• Known human immunodeficiency virus (HIV) (HIV1/2antibodies) or active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA \[qualitative\]).
• Participants with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible

Sponsors & Collaborators

• Breast Cancer Trials, Australia and New Zealand: lead

Study Sites (15)

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, 2450, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Nepean Cancer Care Centre

Kingswood, New South Wales, 2747, Australia

Location

Macquarie University

Macquarie Park, New South Wales, 2109, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2310, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Icon Cancer Centre Hobart

Hobart, Tasmania, 7000, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Parkville, Victoria, 3002, Australia

Location

Epworth Richmond Hospital

Richmond, Victoria, 3121, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Related Links

• Breast Cancer Trials, Australia and New Zealand

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tucatinib; pembrolizumab; Trastuzumab; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Heath Badger

  Breast Cancer Trials, Australia and New Zealand

  STUDY DIRECTOR

• Sherene Loi, Prof

  Peter MacCallum Cancer Centre, Australia

  STUDY CHAIR

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: March 1, 2021
• First Posted: March 9, 2021
• Study Start: March 7, 2023
• Primary Completion: June 4, 2025
• Study Completion: June 4, 2025
• Last Updated: June 6, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be made available for request after publication of the main/final study results; no end date. Note that there may be additional circumstances preventing BCT from sharing requested data as outlined in the BCT Data Sharing Guidelines.
• Access Criteria: Researchers need to submit a research proposal (concept@bctrials.org.au) and BCT Data Request Application, which is then assessed by BCT as having appropriate scientific value.

Locations

AU (15)