Phase Ib/II Study of Zanidatamab Plus Tucatinib and Chemotherapy in HER2-Positive Advanced Breast Cancer
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMedSIR
About this trial
The JAZMINE study is a multicenter, open-label, non-comparative, phase Ib/II clinical trial to evaluate safety and preliminary efficacy of zanidatamab in combination with tucatinib and chemotherapy (capecitabine or eribulin mesylate) in HER2-positive advanced breast cancer.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participants must be capable of understanding the purpose of the Study and have signed a written informed consent form (ICF) prior to beginning specific protocol procedures.
Female or male participants ≥ 18 years of age at the time of signing the ICF.
ECOG PS of 0-1.
Minimum life expectancy of ≥ 12 weeks at screening.
Disqualifiers
Participation in another clinical trial, interventional or observational, until the Study's safety visit.
Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation, or experimental agent within ≤ 3 weeks prior to the first dose of Study treatments.
Prior treatment with capecitabine and eribulin.
Known or suspected leptomeningeal disease (LMD) as documented by the investigator.
Trial design
Design model
Parallel
Treatments tested in this trial
Zanidatamab
DrugWill be administered as an intravenous (IV) infusion on Day 1 of each 21-day treatment cycle (Q3W). The dose of zanidatamab will be weight-based: 1800 mg for participants weighing \<70 kg and 2400 mg for participants weighing ≥70 kg. During phase Ib, the dose of zanidatamab will remain constant.
Tucatinib
DrugWill be administered orally at a dose of 300 mg twice daily (BID) on a continuous basis throughout each 21-day treatment cycle. During phase Ib, the dose of tucatinib will remain constant.
Capecitabine
DrugWill be administered orally twice daily (PO BID) on Days 1-14 of each 21-day treatment cycle during phase Ib. Dose escalation will be performed with a starting dose of 750 mg/m² PO BID, with escalation to 1000 mg/m² PO BID based on tolerability. If the 750 mg/m² dose is not well tolerated, capecitabine will be de-escalated to 650 mg/m² PO BID.
Eribulin Mesilate injection
DrugWill be administered intravenously on Days 1 and 8 of each 21-day treatment cycle during phase Ib. Dose escalation will be performed with a starting dose of 1.1 mg/m², with escalation to 1.4 mg/m² based on tolerability. If the 1.1 mg/m² dose is not well tolerated, eribulin will be de-escalated to 0.7 mg/m².
Treatment groups
24 Participants
are divided into 2 treatment groupsGroup A: Zanidatamab and tucatinib in combination with capecitabineExperimental treatment 3 interventions
Group B: Zanidatamab and tucatinib in combination with eribulinExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and capecitabine in participants with HER2-positive ABC (Cohort A).
The maximum tolerated dose (MTD) of zanidatamab administered in combination with tucatinib and capecitabine, as determined by the proportion of DLTs observed. The RP2D will be established based on the MTD, the overall safety and tolerability profile and early efficacy data (Cohort A). Note: To identify the recommended dose, other available data from secondary endpoints may be taken into consideration.
Time frame
24 days2
To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and eribulin in participants with HER2-positive ABC (Cohort B).
The MTD of zanidatamab administered in combination with tucatinib and eribulin, as determined by the proportion of DLTs observed. The RP2D will be established based on the MTD, the overall safety and tolerability profile and early efficacy data (Cohort B).
Time frame
24 daysSecondary outcomes
1
To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed ORR in participants with HER2-positive ABC.
ORR, defined as the number of participants with CR or PR, divided by the number of participants in the analysis population, as assessed by the Investigator per RECIST v.1.1 (Cohort A and Cohort B)
Time frame
Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).2
To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed IC-ORR in participants with HER2-positive ABC.
IC-ORR, defined as the percentage of participants with IC CR or PR, divided by the number of participants in the analysis population, assessed by the Investigator per RANO-BM criteria (Cohort A and Cohort B; only in participants with BM).
Time frame
Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).3
To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed PFS in participants with HER2-positive ABC.
PFS, defined as the period from Study treatment initiation to the first occurrence of documented radiographic disease progression or death from any cause, whichever occurs first, as assessed by the investigator using RECIST v.1.1. criteria (Cohort A and Cohort B).
Time frame
Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).4
To assess the preliminary efficacy of capecitabine-based therapy (Cohort A) and eribulin-based therapy (Cohort B) in combination with zanidatamab and tucatinib in terms of Investigator-assessed IC-PFS in participants with HER2-positive ABC
IC-PFS, defined as the period from treatment initiation to the first occurrence of documented radiographic intracranial progression or death from any cause, whichever occurs first, as assessed by the Investigator per RANO-BM criteria. (Cohort A and Cohort B; only in participants with BM)
Time frame
Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).Locations
Source ClinicalTrials.gov
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