Pembrolizumab + T-DM1 for Breast Cancer

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must be taking: Trastuzumab, Taxane

Must not be taking: CYP3A4 inhibitors, Immunosuppressants

Disqualifiers: Brain metastases, Autoimmune disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of two drugs, pembrolizumab (an immunotherapy drug) and T-DM1 (also known as trastuzumab-DM1, an antibody-drug conjugate), to determine their effectiveness in treating metastatic breast cancer, which has spread beyond the breast. The goal is to assess whether these drugs, when combined, can improve outcomes for patients with HER2-positive breast cancer, a type that tests positive for a protein promoting cancer cell growth. Ideal participants have confirmed stage IV HER2-positive breast cancer and have previously received treatments like trastuzumab and a taxane. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop any biologic or investigational therapy at least 21 days before joining. If you're on bisphosphonates, you can continue taking them during the study. Avoid using potent CYP3A4 inhibitors like ketoconazole and erythromycin while on T-DM1.

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

Research has shown that using pembrolizumab with trastuzumab emtansine (T-DM1) is generally safe and well-tolerated. In earlier studies, patients with advanced breast cancer who hadn't received T-DM1 before were treated with this combination. These studies found the treatment safe, with no major safety issues reported, and it was manageable for the patients.

The studies continue to explore the best dose and any possible side effects, but the combination appears promising in terms of safety. Participants in these studies help researchers understand how these drugs work together, and their involvement is crucial for improving breast cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Pembrolizumab combined with Trastuzumab-DM1 is unique because it leverages a dual approach to treat breast cancer. While standard treatments typically focus on either immune system activation or targeted therapy, this combination uses pembrolizumab to enhance the immune system's ability to detect and destroy cancer cells. At the same time, Trastuzumab-DM1 delivers targeted chemotherapy directly to the cancer cells, minimizing damage to healthy tissues. Researchers are excited about this treatment because it offers the potential for increased effectiveness by combining these two powerful mechanisms, potentially leading to better outcomes for patients.

What evidence suggests that this combination treatment could be effective for metastatic breast cancer?

This trial will evaluate the combination of pembrolizumab and T-DM1 for patients with advanced breast cancer. Studies have shown that using pembrolizumab with T-DM1 is safe and manageable. Pembrolizumab helps the body's immune system fight cancer, while T-DM1 targets cancer cells directly, aiming to avoid damage to normal cells. Research has shown that T-DM1 alone is more effective than trastuzumab, another breast cancer treatment, especially for HER2-positive breast cancer. Although early data is still being gathered, these findings suggest that combining these treatments might improve patient outcomes by using both immune and targeted methods. ^{3 4 6 7 8}

Who Is on the Research Team?

Sara Tolaney, MD MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with stage IV breast cancer that has spread, who have previously been treated with trastuzumab and a taxane. They must not be pregnant or breastfeeding, agree to use contraception, and have no severe allergies to the drugs being tested. Participants should not have untreated brain metastases or active infections requiring IV antibiotics.

Inclusion Criteria

Your heart's pumping ability must be normal, as checked by a heart ultrasound or MUGA scan within 28 days before starting the study drug.

The bone abnormalities cannot be accurately measured.

I have had radiation therapy before, either for early-stage or advanced cancer.

Exclusion Criteria

I am not taking strong CYP3A4 inhibitors while on T-DM1 treatment.

I am on long-term steroids or other drugs that weaken my immune system.

I have brain metastases that are either untreated, causing symptoms, or need treatment for symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Pembrolizumab and T-DM1 intravenously on day 1 of each 3-week cycle

2 years

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for overall survival and disease progression

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Trastuzumab-DM1

Trial Overview

The study tests Pembrolizumab in combination with Trastuzumab emtansine (T-DM1) as a treatment for metastatic breast cancer. It aims to see if this drug duo can help patients whose tumors are HER2 positive and who may have had prior treatments.

How Is the Trial Designed?

Group I: Pembrolizumab Combine With Trastuzumab Emtansine Experimental Treatment 2 Interventions

* Pembrolizumab will be administered intravenousely in clinic on day 1 of each 3-week cycle * Pembrolizumab will be administered prior to T-DM1 administration * Pembrolizumab will be given at a predetermine dose * T-DM1 will be administered intravenousely in clinic on day 1 of each 3-week cycle * T-DM1 will be given at a predetermine dose

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9577940/

Phase Ib study of pembrolizumab in combination with ...

Conclusions. T-DM1 plus pembrolizumab was a safe and tolerable regimen. Ongoing trials will define if there is a role for checkpoint inhibition ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.1046

A phase Ib study of pembrolizumab (pembro) plus ...

We conducted a phase 1 trial to determine the safety and explore the efficacy of T-DM1 plus pembro. Methods: Eligible patients (pts) had MBC ...

3.

docwirenews.com

docwirenews.com/post/pembrolizumab-plus-trastuzumab-pertuzumab-shows-promise-in-her2-positive-breast-cancer

Pembrolizumab Plus Trastuzumab/Pertuzumab Shows ...

“Accumulating evidence indicates that about 30%–40% of patients with HER2-positive early breast cancer might achieve excellent outcomes without ...

4.

targetedonc.com

targetedonc.com/view/adjuvant-t-dm1-continues-to-outperform-trastuzumab-in-her2-positive-early-breast-cancer

Adjuvant T-DM1 Continues to Outperform Trastuzumab in ...

Adjuvant T-DM1 Continues to Outperform Trastuzumab in HER2-Positive Early Breast Cancer · Distant recurrence: 21.5% and 14.7% in the trastuzumab ...

5.

pmc.ncbi.nlm.nih.gov

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

Emerging Targeted Therapies for HER2-Positive Breast Cancer

Particularly for HER2-low breast cancer, T-DM1 showed limited efficacy, but there are no prospective clinical trials [95].

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36252998/

Phase Ib study of pembrolizumab in combination with ...

Conclusions: T-DM1 plus pembrolizumab was a safe and tolerable regimen. Ongoing trials will define if there is a role for checkpoint inhibition in the ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03032107

NCT03032107 | A Study Of Pembrolizumab In ...

This study will determine what amount (or dose) of Pembrolizumab and of T-DM1 is safe for people to take and what effects, good or bad, this combination may ...

8.

dana-farber.org

dana-farber.org/clinical-trials/16-492

A Phase 1b study of pembrolizumab in combination with ...

This research study is studying a combination of drugs as a possible treatment for metastatic breast cancer. The interventions involved in this study are: ...