A Phase II Study of the Safety, Tolerability and Antitumor Activity of Tucatinib in Combination With Eribulin and Trastuzumab in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer

Plain English Summary

Tucatinib+Trastuzumab+Eribulin in HER2+ MBC is a Phase 2 clinical trial sponsored by Criterium, Inc. studying Breast Cancer, Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer. This trial is testing a combination of three drugs: tucatinib (taken by mouth), eribulin (given by IV), and trastuzumab (given by IV). It is for patients with HER2-positive breast cancer that has spread and cannot be removed by surgery, and who have already been treated with certain other therapies. Participation involves receiving the study drugs and regular medical check-ups to monitor for side effects and tumor response. Alternative treatments may include other chemotherapy drugs, targeted therapies, or immunotherapy, depending on the patient's specific situation and prior treatments. The trial aims to enroll 30 participants.

Official Summary

The purpose of this study is to evaluate the safety and efficacy of the three-drug combination of tucatinib, trastuzumab, and eribulin in patients with de novo and recurrent unresectable metastatic HER-2/neu positive breast cancer as assessed by ORR, PFS and OS after prior treatment with a taxane, trastuzumab, and T-DM1.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you have HER2-positive breast cancer that has spread, cannot be removed, and you've had prior treatment with trastuzumab deruxtecan. You cannot join if you are allergic to any of the study drugs, have certain heart conditions, or have brain metastases that require immediate treatment. You must be at least 18 years old and have a good general health status (ECOG 0-2) with a life expectancy of at least 6 months. Your liver, blood counts, and heart function must meet specific laboratory and test requirements. This trial is studying Breast Cancer, Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe and well-tolerated the combination of drugs is, and how effectively it controls the cancer's growth. The specific primary outcome measures are: To assess the safety and tolerability of tucatinib in combination with eribulin and trastuzumab in patients with unresectable or recurrent metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, and trastuzumab deruxtecan. (2 years); Evaluate the relative toxicity/tolerability of these therapeutic agents when used in combination in this patient cohort (2 years). 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 that has stopped responding to previous therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Breast Cancer, Pretreated Unresectable Locally Advanced or Metastatic HER2+ Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant market of patients with advanced HER2+ breast cancer, exploring a novel combination that could offer a new treatment avenue if successful. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of this combination therapy compared to other available treatments. Understand that participation involves regular clinic visits for drug infusions, blood tests, scans, and monitoring for side effects. Be prepared for potential side effects and discuss any new or worsening symptoms with your healthcare team immediately. This trial is currently recruiting participants. The trial is being conducted at 6 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: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 30 participants

Interventions

• DRUG: Tucatinib — taken orally
• DRUG: Eribulin — taknen intravenously
• DRUG: Trastuzumab — taken intravenously

Primary Outcomes

• To assess the safety and tolerability of tucatinib in combination with eribulin and trastuzumab in patients with unresectable or recurrent metastatic HER2+ breast cancer who have had prior treatment with trastuzumab, and trastuzumab deruxtecan. (2 years)
• Evaluate the relative toxicity/tolerability of these therapeutic agents when used in combination in this patient cohort (2 years)

Secondary Outcomes

• Evaluate efficacy against HER2 + metastatic breast cancer (2 years)
• Evaluate efficacy against CNS disease (2 years)
• Efficacy in patients who have had prior tucatinib (2 years)
• Efficacy in treating CNS disease (2 years)

Full Eligibility Criteria

Inclusion Criteria:

1. Histologically confirmed HER2+ breast carcinoma, with HER2+ defined by in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC)
2. Have received previous treatment with trastuzumab deruxtecan in the metastatic setting or have recurred within 6 months of receiving this treatment in the adjuvant or neoadjuvant setting. Prior taxane, capecitabine and T-DM1 are not required. Prior tucatinib therapy is allowed. Patients for whom Trastuzumab is contraindicated are not permitted. Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by site investigator),or be intolerant of last systemic therapy.
3. Have measurable or non-measurable disease assessable by RECIST 1.1
4. Be at least 18 years of age at time of consent.
5. Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0,1 or 2
6. Have a life expectancy of at least 6 months, in the opinion of the site investigator.
7. Have adequate hepatic function as defined by the following:

   1. Total bilirubin ≤1.5 X upper limit of normal (ULN), except for patients with known Gilbert's disease, who may enroll if the conjugated bilirubin is ≤1.5 X ULN
   2. Transaminases \[aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT)\] ≤ 2.5 X ULN (≤ 5 X ULN if liver metastases are present)
8. Have adequate baseline hematologic parameters as defined by:

   1. Absolute neutrophil count (ANC) ≥ 1.5 x 103/µL
   2. Platelet count ≥ 100 x 103/µL; patients with stable platelet count from 75- 100 x 103/µL may be included with approval from medical monitor,
   3. Hemoglobin ≥ 9 g/dL
   4. In patients transfused before study entry, transfusion must be ≥ 14 days prior to start of therapy to establish adequate hematologic parameters independent from transfusion support,
9. Have creatinine clearance ≥ 50 mL/min as calculated per institutional guidelines or, in patients ≤ 45 kg in weight, a serum creatinine within institutional normal limits,
10. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN unless on medication known to alter INR and aPTT. (Note: Warfarin and other coumarin derivatives are prohibited.)
11. Have left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks prior to first dose of study treatment.
12. If female of childbearing potential, must have a negative result of serum or urine pregnancy test performed within 7 days prior to first dose of study treatment. A woman is considered of childbearing potential, i.e. fertile, following menarche and until becoming post- menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.

    NOTE: Postmenopausal patients with known β-HCG secreting tumors may be eligible when β-HCG-based urine or serum pregnancy tests yield false positive if they meet the definition of postmenopausal state and have a negative uterine ultrasound
13. Women of childbearing potential (as defined above) and men with partners of childbearing potential must agree to use a highly effective birth control method, i.e., methods that achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal); progestogen- only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable); intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion/ligation; vasectomized partner; or sexual abstinence. Male patients with partners of childbearing potential must use barrier contraception. All study patients should practice effective contraception, as described above, starting from the signing of informed consent until 7 months after the last dose of study medication or investigational medicinal product.
14. Patient must provide signed informed consent per a consent document that has been approved by an institutional review board or independent ethics committee (IRB/IEC) prior to initiation of any study-related tests or procedures that are not part of standard-of-care for the patient's disease.
15. Patients must be willing and able to comply with study procedures.

CNS Inclusion - Based on screening contrast brain magnetic resonance imaging (MRI), patients must have one of the following:

1. No evidence of brain metastases
2. Untreated brain metastases not needing immediate local therapy. For patients with untreated CNS lesions \> 2.0 cm on screening contrast brain MRI, d

Trial Locations

• University of Colorado, Aurora, Colorado, United States
• George Washington Medical Faculty Associates, Washington D.C., District of Columbia, United States
• New Mexico Cancer Care Alliance, Albuquerque, New Mexico, United States
• Swedish Cancer Institute, Issaquah, Washington, United States
• Cancer Care Northwest, Spokane Valley, Washington, United States
• University of Wisconsin Carbone Cancer Center, Madison, Wisconsin, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-Positive Breast Cancer
• Metastatic Breast Cancer
• Locally Advanced Breast Cancer
• Unresectable Breast Cancer
• Trastuzumab Resistance
• HER2-Amplified Cancers
• Oncology
• Medical Oncology
• Targeted Cancer Therapy

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