PHASE IB/II STUDY TO EVALUATE SAFETY AND PRELIMINARY EFFICACY OF ZANIDATAMAB IN COMBINATION WITH TUCATINIB AND CHEMOTHERAPY (CAPECITABINE OR ERIBULIN MESYLATE) IN HER2-POSITIVE ADVANCED BREAST CANCER

Plain English Summary

Phase Ib/II Study of Zanidatamab Plus Tucatinib and Chemotherapy in HER2-Positive Advanced Breast Cancer is a Phase 2 clinical trial sponsored by MedSIR studying HER 2 Positive Advanced Breast Cancer, Breast Cancer. This trial is testing a combination of drugs: zanidatamab, tucatinib, and chemotherapy (either capecitabine or eribulin mesylate). It is for patients with HER2-positive advanced breast cancer that has progressed after at least one prior anti-HER2 therapy. Participation involves receiving the study drugs intravenously and orally, with regular follow-up visits. Alternative treatments may include other chemotherapy regimens or targeted therapies depending on prior treatments and disease progression. The trial aims to enroll 24 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with HER2-positive advanced breast cancer. Patients whose cancer has progressed after 1 to 3 prior treatments for advanced disease. Individuals with good general health and organ function (liver, kidney, bone marrow). Patients must not have brain metastases that require immediate treatment or are larger than 2 cm without discussion with the study doctor. This trial is studying HER 2 Positive Advanced Breast Cancer, Breast Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures will help determine the best dose of the study drugs to use in future trials, aiming to find a safe and effective combination for patients. The specific primary outcome measures are: To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and capecitabine in participants with HER2-positive ABC (Cohort A). (24 days); To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and eribulin in participants with HER2-positive ABC (Cohort B). (24 days). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for new treatment options for patients with advanced HER2-positive breast cancer who have limited treatment choices after standard therapies have stopped working. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets HER 2 Positive Advanced Breast Cancer, Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant market for advanced breast cancer treatments, with the combination of zanidatamab and tucatinib representing a novel approach that could offer a competitive advantage Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer and treatment history. Be prepared for regular clinic visits for drug infusions, oral medication, and monitoring of your health and response to treatment. Understand that this is an open-label study, meaning both you and your doctor will know which treatments you are receiving. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 24 participants

Interventions

• DRUG: Zanidatamab — Will 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.
• DRUG: Tucatinib — Will 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.
• DRUG: Capecitabine — Will 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.
• DRUG: Eribulin Mesilate injection — Will 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.

Primary Outcomes

• To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and capecitabine in participants with HER2-positive ABC (Cohort A). (24 days)
• To determine the recommended phase II dose (RP2D) of zanidatamab in combination with tucatinib and eribulin in participants with HER2-positive ABC (Cohort B). (24 days)

Secondary Outcomes

• 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. (Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).)
• 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. (Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).)
• 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. (Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).)
• 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 (Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).)
• To determine the safety and toxicity profile according to the NCI-CTCAE v.5.0 of capecitabine-based therapy in combination with zanidatamab and tucatinib in participants with HER2-positive ABC (Cohort A). (Until EoS (9 months after last participant in phase II starts treatment unless premature termination of the Study).)

Full Eligibility Criteria

Inclusion Criteria:

1. 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.
2. Female or male participants ≥ 18 years of age at the time of signing the ICF.
3. ECOG PS of 0-1.
4. Minimum life expectancy of ≥ 12 weeks at screening.
5. Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent.
6. Locally confirmed HER2-positive breast cancer (immunohistochemistry \[IHC\] score of 3+ or ICH score of 2+ with confirmation of HER2 amplification by in situ hybridization \[ISH\]) per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 criteria on the most recent analyzed biopsy.
7. Evaluable disease by RECIST v.1.1.
8. All participants need to have experienced disease progression after at least one line, but no more than 3 lines, of anti-HER2-therapy for advanced disease.
9. Able to provide the most recently available FFPE tumor tissue blocks at the time of inclusion.

   Note: If no archived sample is available participant eligibility should be discussed with the Medical Monitor.
10. Able to provide blood samples at the established time points.
11. Participant must have adequate bone marrow, coagulation, liver, and renal function:

    * Absolute neutrophil count (ANC) ≥ 1.5 × 103/μL, platelet count ≥ 100 x 103/μL, and hemoglobin (Hgb) ≥ 9 g/dL. Transfusion must be ≥ 14 days prior to starting therapy to establish adequate hematologic parameters independent of transfusion support. Participants with chronic anemia (other than autoimmune hemolytic anemia) that is supported by intermittent red blood cell transfusions are eligible.
    * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × the upper limit of normal (ULN), unless on medication known to alter INR and aPTT (Note: Warfarin and other coumarin derivatives are prohibited).
    * Total bilirubin ≤ 1.5 × ULN or ≤ 3.0 × ULN for participants with Gilbert's disease (if the conjugated bilirubin is ≤ 1.5 × ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN (for participants with liver metastases, AST and ALT ≤ 5.0 × ULN are acceptable).
    * Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min calculated per institutional guidelines.
12. Female participants of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of Study treatments.

    Note: A woman is considered of childbearing potential, i.e., fertile, following menarche until post-menopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause. For participants with a hormonal profile compatible with menopausal status, they will be discussed with the medical monitor.
13. Female participants of childbearing potential and male participants with a partner of childbearing potential must agree to use two methods of birth control with a failure rate of less than 1% per year starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments.

    Note: See Section 8.4.2 for allowed contraceptive methods.
14. Female participants must refrain from oocyte donation and breastfeeding, and male participants must not donate or bank sperm starting at the screening, throughout the study, and for 12 months after the last dose of Study treatments.
15. Participants must be accessible for treatment and follow-up visits.

Specific inclusion criteria for BMs:

1. Stable BMs were defined as BMs radiographically stable for ≥4 weeks since completion of treatment.
2. Untreated BM without immediate need for local therapy. For participants with untreated CNS lesions \> 2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment.
3. BMs that had progressed since local CNS therapy, with no clinical indication for immediate retreatment with local therapy.
4. Washout periods before the first day of dosing were \>7 days for SRS or gamma knife, and \>24 days for WBRT, respectively. The use of systemic corticosteroids for control of symptoms of BM is not permitted if the total daily dose is \> 2 mg of dexamethasone (or equivalent). However, participants on a chronic stable dose of ≤ 2 mg total daily of dexamethasone (or equivalent) may be eligible following discussion and approval by the medical monitor. Participants receiving an anticonvulsant therapy must be on stable dosing regimen for ≥ 14 days prior to the first dose of Study treatment.

Specific inclusion criteria for phase II At least 50% of participants enrolled in phase II must ha

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-Positive Breast Cancer
• Advanced Breast Cancer
• Metastatic Breast Cancer
• HER2-Amplified Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• Triple-Negative Breast Cancer (if HER2-positive component)
• Oncology
• Medical Oncology
• Gastrointestinal Cancers (as HER2 is also a target)

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