Data

An investigator-initiated, non-randomised, phase II study of combination CTLA-4 and PD-L1 blockade in combination with HER2 blockade in advanced HER2-positive breast cancers that have progressed on prior trastuzumab-based therapy (BCT 1703 DIAmOND)

Breast Cancer Trials (BCT)

Dataset description

THIS DATASET IS NOT YET AVAILABLE FOR SHARING. Dataset of 72 patients with advanced HER2-positive breast cancer that have progressed on prior trastuzumab-based therapy. Three cohorts: Cohort 1: ER-positive patients; Cohort 2: ER-negative patients; both cohorts treated with 16 week induction phase with tremelimumab 75mg q4w IV, durvalumab 1500mg q4w IV and trastuzumab 2mg/kg q1w IV. Followed by Treatment phase (weeks 17-52) durvalumab 1120mg q3wIV & trastuzumab 6mg/kg q3w IV. Cohort 3: all patients treated with tremelimumab priming dose single 300 mg dose, with durvalumab 1120mg administered with tremelimumab on Day 1 and continued q3w for up to 18 doses. Primary objectives: Cohorts 1 & 2 - Percentage of participants alive and progression free, determined by RECIST 1.1; Cohort 3 - Objective response rate by RECIST 1.1.
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Source Study

Funding

Other Collaborative groups,Breast Cancer Trials

Scientific enquiries

A/Prof Sherene Loi

Brief Summary

This study aims to find out if the combination of trastuzumab (anti-HER2 therapy) with durvalumab (PD-L1 inhibitor) and tremelimumab (CTLA4 inhibitor) will reactivate anti-tumour immune response and improve clinical outcomes in trastuzumab-resistant, advanced HER2-positive breast cancer. Who is it for? You may be eligible for this study if you are 18 years or older, male or female, and have HER2-positive metastatic or incurable breast cancer that has progressed on previous trastuzumab treatment. ....
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Key Inclusion Criteria

1) Written informed consent prior to performing any protocol-related procedures, including screening evaluations. 2) Written consent to biological material submission. 3) Female or Male, age >= 18 years. 4) Local histologically confirmed HER2-positive on a recent biopsy. This can be as per ASCO-CAP guidelines: IHC testing with a result of IHC 3+, or IHC 2+ISH testing with ERBB2-amplification as demonstrated by ratio ERBB2/centromeres >= 2.0 or mean gene copy number >= 6, unresectable loco-region ....
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Key Exclusion Criteria

1) Previous history of primary HER2 non-amplified invasive breast cancer (of different subtype) in the last 3 years. 2) Participation in another clinical study with an investigational product during the last 4 weeks before enrolment. 3) Prior cytotoxic treatment less than 2 weeks before the planned first dose of Durvalumab and Tremelimumab. 4) Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA-4, including tremelimumab. 5) No FFPE material to centrally ass ....
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Can healthy volunteers participate?

No

 

Population

Sample Size    72

Min. age    18 Years

Max. age    No limit

Sex    Both males and females

Condition category    Advanced HER2-positive breast cancer

Condition code    Cancer

Intervention

Intervention code Treatment: Drugs

TREMELIMUMAB 75 mg DOSE ER-POSITIVE COHORT AND ER-NEGATIVE COHORT Induction phase (Weeks 1-16): * Tremelimumab 75 mg every 4 weeks for 4 doses (intravenous); * Durvalumab 1500 mg every 4 weeks for 4 doses (intravenous); * Trastuzumab 2mg/kg every week for 16 weeks (intravenous). Tremelimumab will be administered first. Durvalumab infusion will start approximately 1 hour after the end of tremelimumab infusion. The duration will be approximately 1 hour for each infusion. A 1 hour observation perio ....
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Comparison

Control group Uncontrolled

None

Outcomes

Outcome: Percentage of participants alive and progression free, determined by RECIST 1.1 for the Tremelimumab 75 mg dose ER-positive cohort and ER-negative cohort
Timepoint: At 12 months from study registration.

Outcome: Objective response rate by RECIST 1.1 for the Tremelimumab single 300 mg priming dose cohort.
Timepoint: Assessed at each cycle (every3 weeks) until 12 months from study registration

Study Protocol: Not Available
Data Dictionary: Not Available

Will individual participant data (IPD) for this trial be available?

yes

What data in particular will be shared?

Anonymised Individual Patient Data (IPD) collected during the trial.

When will data be available?

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 .

Available to whom?

Researchers who submit a research proposal and BCT Data Request Application, which is assessed by BCT to have appropriate scientific value. Refer to the BCT Data Sharing Guidelines

Available for what types of analyses?

To achieve the aims in the approved proposal.

Source study information is derived from the Australian New Zealand Clinical Trials Registry (ANZCTR). For more information on the ANZCTR, please see anzctr.org.au