Tucatinib + Doxil for Breast Cancer

Recruiting at 7 trial locations

Overseen By Sarah Cannon Development Innovations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SCRI Development Innovations, LLC

Must not be taking: CYP2C8 inhibitors, CYP3A4 inducers

Disqualifiers: Uncontrolled hypertension, Diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: Up to 40 months

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining tucatinib and Doxil (a form of chemotherapy) to treat a specific type of breast cancer that is locally advanced or has metastasized. The study aims to determine the combination's effectiveness and potential side effects. Individuals diagnosed with HER2+ breast cancer who have already tried at least one treatment might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant findings.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot use strong CYP2C8 inhibitors or strong CYP3A4 inducers within 5 days before starting the study treatment. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that the combination of tucatinib and Doxil is likely to be safe for humans?

Research has shown that tucatinib is generally manageable for patients. The FDA approved it in 2020 for treating advanced HER2-positive breast cancer, confirming its safety for individuals with similar conditions.

In a study involving 71 patients with advanced breast cancer, the drug Doxil (also known as Caelyx) achieved a 31% success rate in shrinking tumors. Although the study primarily assessed the drug's effectiveness, patients generally tolerated the side effects well.

Thus far, combining tucatinib with Doxil has not resulted in any unexpected side effects. However, individual experiences may vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tucatinib and Doxil for breast cancer because it offers a novel approach to treatment. Unlike typical therapies that primarily target estrogen or HER2 receptors, tucatinib specifically inhibits the HER2 protein with high precision, potentially reducing damage to healthy cells. When combined with Doxil, a form of chemotherapy delivered as a liposomal formulation to minimize side effects, this treatment aims to provide a more effective and tolerable option for patients. This combination could offer enhanced effectiveness and a better side effect profile compared to existing treatments.

What evidence suggests that the combination of tucatinib and Doxil could be effective for breast cancer?

Research shows that tucatinib, when combined with chemotherapy, effectively treats advanced HER2-positive breast cancer. Studies indicate that tucatinib prolongs the period before the cancer worsens. Doxil, a type of chemotherapy, also effectively treats advanced breast cancer and is safer than traditional chemotherapy, causing fewer heart-related side effects. In this trial, participants will receive a combination of tucatinib and Doxil, which could offer a strong treatment option for HER2-positive breast cancer based on these findings. ^{6 7 8 9 10}

Who Is on the Research Team?

Erika Hamilton, MD

Principal Investigator

SCRI Development Innovations, LLC

Are You a Good Fit for This Trial?

This trial is for adults with HER2+ advanced or metastatic breast cancer who've had at least one anti-HER2 therapy. They must be in good health, not planning to have children, and able to use two forms of contraception. Excluded are those with other active cancers, recent major surgery, certain infections like HIV or hepatitis B/C, uncontrolled diseases such as hypertension or diabetes, and specific heart conditions.

Inclusion Criteria

My blood counts are within a healthy range.

Your heart is pumping blood effectively, as shown in a recent heart test.

My brain MRI meets the specific criteria for brain metastases.

Exclusion Criteria

Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol

I don't have large brain tumors, uncontrolled seizures, or certain brain diseases.

I do not have stomach or bowel problems that affect how my body handles medicine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Safety Lead-in

First 6 patients are evaluated weekly for one treatment cycle to ensure the regimen is safe and tolerable

4 weeks

4 visits (in-person)

Treatment

Participants receive tucatinib 300mg by mouth twice daily continuously in combination with Doxil 40mg/m2 intravenously on day 1 of each 28-day cycle

Up to 40 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Doxil
• Tucatinib

Trial Overview The study tests the effectiveness and side effects of combining tucatinib with Doxil in treating HER2+ breast cancer that has spread. Participants will receive both medications and researchers will monitor how well this combination works compared to previous treatments they've received.

How Is the Trial Designed?

Group I: Tucatinib Experimental Treatment Arm Experimental Treatment 2 Interventions

Participants will receive tucatinib 300mg by mouth twice daily continuously in combination with Doxil 40mg/m2 given intravenously on day 1 of each cycle. Cycles will be 28 days. Up to 36 participants will be enrolled in this Phase 2 study.

Doxil is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Doxil for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Approved in European Union as Caelyx for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma
• Breast cancer

Approved in Canada as Doxorubicin liposomal for:

• Ovarian cancer
• AIDS-related Kaposi's sarcoma
• Multiple myeloma

Who Is Running the Clinical Trial?

SCRI Development Innovations, LLC

Lead Sponsor

Trials

193

Recruited

13,800+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Published Research Related to This Trial

The combination of tucatinib, a selective HER2 tyrosine kinase inhibitor, with the antibody-drug conjugate T-DM1 significantly enhances antitumor activity in HER2-positive breast cancer, including cases resistant to T-DM1 alone.

Tucatinib improves the effectiveness of T-DM1 by increasing the internalization and breakdown of HER2, leading to better inhibition of tumor growth and improved survival outcomes, particularly in patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HER2-Selective and Reversible Tyrosine Kinase Inhibitor Tucatinib Potentiates the Activity of T-DM1 in Preclinical Models of HER2-positive Breast Cancer. Olson, D., Taylor, J., Willis, K., et al.[2023]

In patients with HER2-positive metastatic breast cancer who had previously received multiple treatments, tucatinib combined with trastuzumab and capecitabine significantly improved progression-free survival at 1 year (33.1% vs. 12.3% for placebo) and overall survival at 2 years (44.9% vs. 26.6% for placebo).

Tucatinib was particularly effective for patients with brain metastases, showing a 1-year progression-free survival of 24.9% compared to 0% in the placebo group, although it was associated with higher rates of adverse events like diarrhea and elevated liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. Murthy, RK., Loi, S., Okines, A., et al.[2021]

Tucatinib is a highly selective oral HER2-targeted small-molecule inhibitor that effectively blocks HER2 kinase activity with a potency significantly greater than that for the related EGFR receptor, making it a promising treatment for HER2-driven cancers.

In preclinical studies, tucatinib demonstrated strong antitumor activity both as a standalone treatment and in combination with other therapies like trastuzumab or docetaxel, leading to improved tumor regression rates in HER2+ cancer models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Activity of HER2-Selective Tyrosine Kinase Inhibitor Tucatinib as a Single Agent or in Combination with Trastuzumab or Docetaxel in Solid Tumor Models. Kulukian, A., Lee, P., Taylor, J., et al.[2021]

In a multicenter phase II study involving 71 patients with metastatic breast cancer, Caelyx (Doxil) demonstrated an overall response rate of 31%, with 16 patients achieving a partial or complete response, indicating its efficacy in treating advanced breast cancer.

The safety profile of Caelyx was favorable, with significant neutropenia and mucositis occurring in only 10% of treatment cycles, and a lower incidence of severe skin toxicity at a dose of 45 mg/m2 every 4 weeks, suggesting it is well-tolerated and suitable for combination chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of advanced breast cancer with sterically stabilized liposomal doxorubicin: results of a multicenter phase II trial. Ranson, MR., Carmichael, J., O'Byrne, K., et al.[2017]

In a phase II study involving 34 patients with metastatic breast cancer, the combination of paclitaxel and liposomal doxorubicin was effective in 73% of patients, showing a high response rate with 7 complete and 18 partial responses.

The treatment had a moderate toxicity profile, with only a small number of severe side effects reported, including 2 toxic deaths (6%), indicating that while effective, careful monitoring for serious adverse effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. Vorobiof, DA., Rapoport, BL., Chasen, MR., et al.[2015]

In a phase II study involving 35 patients with locally advanced breast cancer, the combination of paclitaxel and pegylated liposomal doxorubicin showed significant efficacy, with 71% of patients responding to treatment, including a 17% complete response rate.

The primary side effect observed was skin toxicity, particularly palmar-plantar erythrodysesthesia, but these effects were manageable, and there were no treatment-related deaths, indicating a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant chemotherapy with a combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel in locally advanced breast cancer: a phase II study by the Hellenic Cooperative Oncology Group. Gogas, H., Papadimitriou, C., Kalofonos, HP., et al.[2020]

Tucatinib, at a recommended phase 2 dose of 300 mg twice daily, demonstrated acceptable safety with manageable side effects, including diarrhea and nausea, in a study of 60 patients with HER2-positive breast cancer.

The combination of tucatinib with capecitabine or trastuzumab showed promising anti-tumor activity, with an objective response rate of 83% for tucatinib plus capecitabine, indicating its potential as an effective treatment option for patients who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Murthy, R., Borges, VF., Conlin, A., et al.[2022]

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

Doxil-liposomal topotecan (Topophore C) combinations showed promising synergistic effects in treating ovarian cancer, particularly in the ES-2 and OVCAR-3 cell lines, indicating enhanced therapeutic potential compared to individual drugs.

In animal models, the combination of Topophore C and Doxil significantly increased median survival time to 52 days, compared to 18 days for untreated animals and 40 days for Topophore C alone, demonstrating the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Patankar, NA., Pritchard, J., van Grinsven, M., et al.[2018]

Tucatinib's metabolism is primarily influenced by the enzyme CYP2C8, with significant increases in its concentration when co-administered with inhibitors like itraconazole and gemfibrozil, while its levels decrease with the CYP3A4 inducer rifampin.

The study found that tucatinib is well tolerated in healthy volunteers, and potential drug-drug interactions can be managed by avoiding strong inducers or inhibitors of CYP enzymes and adjusting doses of co-administered medications as necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteer s. Topletz-Erickson, A., Lee, A., Rustia, EL., et al.[2022]

In a phase II study involving 63 patients with ovarian cancer, pegylated liposomal doxorubicin (Doxil) showed a response rate of 19% in patients with measurable disease and a median overall survival of 10 months, indicating its efficacy in a heavily pretreated population.

Doxil was well tolerated, with manageable side effects; serious toxicities were relatively low, and nausea and vomiting were uncommon, suggesting a favorable safety profile compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of liposomal doxorubicin in advanced gynecologic cancers. Israel, VP., Garcia, AA., Roman, L., et al.[2013]

In a study of 42 patients receiving cumulative doses of pegylated liposomal doxorubicin (doxil) exceeding 500 mg/m2, none developed clinical congestive heart failure, indicating a favorable safety profile for higher doses compared to traditional doxorubicin.

While five patients experienced a drop in left ventricular ejection fraction (LVEF), the overall risk of cardiomyopathy appears significantly lower with doxil, even in patients previously treated with doxorubicin, suggesting that doxil may be a safer option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Safra, T., Muggia, F., Jeffers, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9336354/

Treatment of advanced breast cancer with sterically ... Conclusion: Caelyx is an active agent in advanced breast cancer with a safety profile that differs markedly from nonliposomal doxorubicin. A regimen of 45 mg/m2 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3619536/

Liposomal Doxorubicin in the Treatment of Breast Cancer ... Liposomal anthracyclines have achieved highly efficient drug encapsulation and they have proven to be effective and with reduced cardiotoxicity, as a single ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S092375341964144X

Reduced cardiotoxicity and comparable efficacy in a phase ... In first-line therapy for MBC,PLD provides comparable efficacy to doxorubicin, with significantly reducedcardiotoxicity, myelosuppression, vomiting andalopecia.

4. nature.com nature.com/articles/s41598-025-94291-9

Reducing toxicity and enhancing efficacy of doxorubicin by ... This study investigates the efficacy and toxicity profiles of pegylated liposomal doxorubicin (Doxil) compared to conventional doxorubicin.

5. bmjoncology.bmj.com bmjoncology.bmj.com/content/4/1/e000573

Thirty years from FDA approval of pegylated liposomal ... Overall clinical benefit rate from this series was 63% with an objective response in 31% of the patients and stabilisation in 32% of the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05748834

NCT05748834 | Study of Tucatinib and Doxil in ... This is a Phase 2, open-label, single-arm study evaluating the combination of tucatinib with Doxil in participants with HER2+ breast cancer who have received at ...

7. withpower.com withpower.com/trial/phase-2-breast-neoplasms-2-2023-d70fd

Tucatinib + Doxil for Breast Cancer In a multicenter phase II study involving 71 patients with metastatic breast cancer, Caelyx (Doxil) demonstrated an overall response rate of 31%, with 16 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10093019/

Emerging Targeted Therapies for HER2-Positive Breast Cancer Given the results of the phase 3 HER2CLIMB [175] trial, tucatinib was approved by the FDA in 2020 to treat patients with metastatic HER+ breast cancer.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04457596

Study Details | NCT04457596 | T-DM1 and Tucatinib ... This phase III trial studies how well trastuzumab emtansine (T-DM1) and tucatinib work in preventing breast cancer from coming back (relapsing)

10. ema.europa.eu ema.europa.eu/en/documents/assessment-report/tukysa-epar-public-assessment-report_en.pdf

Tukysa; INN-tucatinib - EMA Once HER2+ breast cancer has metastasised, the estimated 5-year overall survival (OS) rate ranges from 15% to 26% (American Cancer Society 2018; ...