T-DM1 + Pertuzumab for Breast Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Potent CYP3A4 inhibitors

Disqualifiers: Pregnancy, Active infection, Liver disease, Uncontrolled hypertension, 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: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, T-DM1 (Trastuzumab emtansine or Kadcyla) and Pertuzumab (Perjeta), to treat HER2-positive breast cancer. HER2 is a protein that can make breast cancer more aggressive. The trial aims to determine if these drugs can effectively combat this type of cancer. People with HER2-positive breast cancer, particularly those with a tumor size of 2 cm or larger, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to significant advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that potent CYP3A4 inhibitors (a type of drug that affects how your body processes certain medications) should be avoided during the study. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both T-DM1 and Pertuzumab are generally well-tolerated by patients. T-DM1 can reduce the risk of breast cancer recurrence by about 50% compared to some other treatments, making it quite effective. However, like all treatments, it can cause side effects. Some patients have experienced low blood counts or liver issues, though these are uncommon.

Pertuzumab is also used to treat HER2-positive breast cancer and has a good safety record. It works well with T-DM1 to target cancer cells more effectively. While side effects can occur, they are usually manageable.

This trial is in a phase that focuses on safety, indicating that T-DM1 and Pertuzumab have undergone sufficient testing to be considered safe for further study. Prospective participants should discuss with their doctor what these findings mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about T-DM1 and Pertuzumab for breast cancer because these treatments offer a novel approach compared to standard options like chemotherapy and HER2-targeted therapies. T-DM1 combines the cancer-killing power of chemotherapy with targeted therapy, delivering the drug directly to cancer cells, which minimizes damage to healthy cells. Pertuzumab adds another layer by blocking a different part of the HER2 receptor, preventing cancer cell growth. This combination aims to enhance treatment effectiveness and reduce side effects, offering new hope for patients.

What evidence suggests that T-DM1 and Pertuzumab could be effective for breast cancer?

In this trial, participants will receive a combination of T-DM1 and Pertuzumab to treat HER2-positive breast cancer. Studies have shown that using T-DM1 and Pertuzumab together can be effective. T-DM1 has improved survival rates compared to older treatments, with patients living without cancer progression for about 9.6 months on average and living overall for about 30.9 months in some cases. Research suggests that adding Pertuzumab to T-DM1 enhances the treatment's effectiveness. Patients who received both drugs experienced significant improvements in their outcomes. These drugs target the HER2 protein, often found in high amounts in certain breast cancers, making the treatment more precise and effective. ^{1 6 7 8 9}

Who Is on the Research Team?

Otto Metzger, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with early-stage HER2+ breast cancer, who are in good health (ECOG 0 or 1), can provide tissue samples, and agree to use contraception. Excluded are those with active infections, liver disease, pregnancy/nursing status, significant neuropathy symptoms, other serious diseases that could interfere with treatment, prior treatment for current breast cancer or recent IV antibiotics.

Inclusion Criteria

The breast imaging should include the armpit on the same side.

I am fully active or can carry out light work.

My breast cancer is HER2-positive, Stage II or III, and my tumor is at least 2 cm big.

Exclusion Criteria

I currently have an infection that is not getting better.

I have not taken IV antibiotics for an infection in the last week.

I have high blood pressure or heart disease that is not well-managed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-DM1 and Pertuzumab every 3 weeks for 6 cycles

18 weeks

6 visits (in-person)

Surgery

Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy

6 weeks

Follow-up

Participants are monitored for disease and survival every 6 months for 5 years and annually until year 10

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Excision of tumor/mastectomy
• Pertuzumab
• T-DM1

Trial Overview The study tests a combination of two drugs: Trastuzumab emtansine (T-DM1) and Pertuzumab as pre-operative treatments for HER2+ breast cancer. It aims to evaluate the effectiveness of this drug duo before surgical interventions like tumor excision or mastectomy.

How Is the Trial Designed?

Group I: T-DM1 and Pertuzumab Experimental Treatment 3 Interventions

T-DM1 3.6 mg per kg of body weight via IV every 3 weeks for 6 doses and Pertuzumab loading dose of 840 mg via IV on Cycle 1 Day 1 followed by maintenance dose of 420 mg via IV every 3 weeks for 6 doses. Excision of tumor/mastectomy of biopsy residual tumor within 42 days of the last cycle of therapy.

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

Approved in European Union as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in United States as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Canada as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Approved in Japan as Perjeta for:

• Early breast cancer
• Metastatic breast cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In T-DM1-resistant HER2-positive breast cancer cells, the combination of trastuzumab and pertuzumab (TRAS + PER) showed enhanced antitumor effects, significantly inhibiting cell proliferation and inducing apoptosis compared to either drug alone.

The study demonstrated that TRAS + PER effectively suppressed tumor growth in a xenograft model of T-DM1-resistant cancer, suggesting it could be a promising treatment option for patients who develop resistance to T-DM1 while maintaining HER2 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination efficacy of pertuzumab and trastuzumab for trastuzumab emtansine-resistant cells exhibiting attenuated lysosomal trafficking or efflux pumps upregulation. Yamashita-Kashima, Y., Shu, S., Osada, M., et al.[2021]

In a phase IIa study involving 64 patients with HER2-positive metastatic breast cancer, the combination of trastuzumab emtansine (T-DM1) and pertuzumab showed an overall objective response rate (ORR) of 41%, with a higher ORR of 57% in first-line patients, indicating promising efficacy for this treatment.

The combination therapy was generally safe, with common side effects including fatigue (61%) and nausea (50%), and no unexpected toxicities were reported, suggesting that this treatment can be administered at full doses without significant safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. Miller, KD., Diéras, V., Harbeck, N., et al.[2022]

In the KRISTINE study involving 444 patients with HER2-positive breast cancer, neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (T-DM1+P) resulted in a lower pathologic complete response rate (44.4%) compared to docetaxel, carboplatin, trastuzumab plus pertuzumab (TCH+P) (55.7%), indicating that while T-DM1+P may be less effective in achieving complete tumor response, it has a better safety profile.

T-DM1+P was associated with significantly fewer grade 3 or greater adverse events (31.8% vs. 67.7% for TCH+P) during neoadjuvant treatment, although it led to more serious adverse events during adjuvant treatment, highlighting the need to balance efficacy and safety when choosing treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. Hurvitz, SA., Martin, M., Jung, KH., et al.[2020]

In the phase III EMILIA trial, trastuzumab emtansine (T-DM1) demonstrated a significantly better safety profile compared to capecitabine plus lapatinib (CAP + LAP) in treating HER2-positive metastatic breast cancer, leading to fewer severe treatment-related adverse events.

The management of adverse events resulted in lower costs for T-DM1 (CAD 3380) compared to CAP + LAP (CAD 6901), indicating that T-DM1 not only provides effective treatment but also offers substantial savings to the Canadian public health-care system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System. Piwko, C., Prady, C., Yunger, S., et al.[2019]

In a phase Ib/IIa study involving patients with HER2-positive metastatic breast cancer (MBC) and locally advanced breast cancer (LABC), the combination of trastuzumab emtansine (T-DM1) with docetaxel showed high efficacy, achieving an 80% objective response rate in MBC and a 60.3% pathologic complete response rate in LABC.

Despite the promising efficacy, nearly half of the patients experienced adverse events (AEs) that required dose modifications, with neutropenia being the most common severe AE, affecting 72% of MBC patients and 29% of LABC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study. Martin, M., Fumoleau, P., Dewar, JA., et al.[2022]

In the phase 3 MARIANNE trial involving 1095 patients with HER2-positive advanced breast cancer, trastuzumab emtansine (T-DM1) demonstrated similar overall survival rates compared to trastuzumab plus a taxane, while showing better tolerability and fewer severe side effects.

Patients receiving T-DM1 had a longer median overall survival when they achieved an objective tumor response, indicating that T-DM1 is a viable first-line treatment option for those unsuitable for taxane-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results from MARIANNE. Perez, EA., Barrios, C., Eiermann, W., et al.[2020]

In a review of six studies involving 996 patients with HER2-positive breast cancer, the addition of pertuzumab to trastuzumab emtansine (T-DM1) ± taxane did not significantly improve objective response or clinical benefit rates compared to T-DM1 alone.

While the combination treatment was associated with increased risks of certain adverse events like diarrhea and rash, it also showed a decreased risk of thrombocytopenia, indicating a complex safety profile that requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the addition of pertuzumab to T-DM1 ± taxane in patients with HER2-positive, locally advanced or metastatic breast cancer: a pooled analysis. Zhang, J., Li, J., Zhu, C., et al.[2022]

In a study involving 27 patients with HER2-positive metastatic breast cancer who had progressed on previous therapies, the combination of ado-trastuzumab emtansine (T-DM1) and neratinib showed promising efficacy, with 63% of evaluable patients achieving an objective response.

The recommended phase II dose for this combination was established as T-DM1 at 3.6 mg/kg and neratinib at 160 mg/d, with manageable safety profiles, although some patients experienced grade 3 toxicities like diarrhea and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10. Abraham, J., Montero, AJ., Jankowitz, RC., et al.[2020]

Citations

1. nature.com nature.com/articles/s41598-025-97923-2

Real-world data on trastuzumab emtansine (TDM1) ... This study aims to provide real-world evidence on the efficacy and safety of TDM1 in HER2-positive MBC patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10232689/

Retrospective Observational Study of Outcomes in HER2 ... Treatment outcomes appeared similar in the 184 patients with pertuzumab exposure before T-DM1. Median TTD was 4.6 months (95% CI 3.5–6.0), ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12210745/

Comparison of T-DM1 and trastuzumab-pertuzumab in ... Based on the introduction of targeted therapy, the prognosis of patients with HER2-positive breast cancer has significantly improved [1, 2].

4. onclive.com onclive.com/view/second-line-t-dm1-worsens-outcomes-for-her2-breast-cancer-in-real-world-study

Second Line T-DM1 Worsens Outcomes for HER2+ Breast ... For example, T-DM1 elicited a higher median progression-free survival (PFS) and OS (9.6 months and 30.9 months, respectively), compared with ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.67.4887

Primary Results From the Phase III MARIANNE Study T-DM1 has demonstrated superior efficacy and improved tolerability compared with the previous standard of care in two phase III trials in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4778787/

Clinical efficacy and safety of T-DM1 for patients with HER2 ... The estimated pooled OR showed significantly improved 2-month, 4-month, and 6-month SPF rates for patients with breast cancer receiving T-DM1 (OR, 2.01; 95% CI, ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1814017

Trastuzumab Emtansine for Residual Invasive HER2 ... In this trial, adjuvant treatment with T-DM1 resulted in a 50% lower risk of recurrence of invasive disease or death than adjuvant continuation ...

8. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)00343-2/fulltext

Safety profile of trastuzumab-emtansine (T-DM1) with ... , demonstrated that adjuvant T-DM1 halved the risk of recurrence of invasive breast cancer or death as compared to trastuzumab alone in patients ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2949820124000237

Utilization and safety of trastuzumab emtansine (T-DM1) Compared with incident breast cancer patients in the general population, those treated with T-DM1 for mBC had 5.7 (95% CI 5.2-5.9) and 10.5 (95% CI 9.1-12.8) ...