Patritumab Deruxtecan for Breast Cancer

Recruiting at 16 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Anti-HER2 therapy

Must not be taking: HER2-targeted tyrosine kinase inhibitors

Disqualifiers: Cardiovascular disease, Pneumonitis, Respiratory compromise, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to approximately 12 months

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether patritumab deruxtecan, a targeted cancer therapy, alone or with other treatments, can treat certain types of breast cancer, specifically those that are HER2 positive and have spread or are inoperable. Researchers aim to determine if the cancer shrinks or disappears in participants and how well they tolerate any side effects. Participants should have advanced or metastatic HER2-positive breast cancer and should have previously tried other treatments without success. As a Phase 1 and Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that the safety of patritumab deruxtecan, when combined with trastuzumab and other treatments, generally aligns with expectations for cancer therapies. In studies, patients tolerated this treatment well, though some side effects occurred. For example, when combined with trastuzumab, some patients developed interstitial lung disease (ILD), a lung condition, but it improved within a few weeks in some cases.

When used with pertuzumab and trastuzumab, about 63.5% of patients experienced serious side effects, similar to those seen with other standard treatments like THP.

In another combination with tucatinib, real-world studies found this treatment more effective than some other options, but detailed safety data for this combination remains limited.

The treatment is in the early stages of research, so while results are promising, safety continues to be closely monitored. Discuss any concerns with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about patritumab deruxtecan for breast cancer because it offers a novel approach compared to current treatments. Unlike standard therapies, which often target the HER2 receptor alone, patritumab deruxtecan is an antibody-drug conjugate that combines an anti-HER3 antibody with a potent chemotherapy agent, allowing it to deliver the drug directly to cancer cells. This targeted delivery could potentially reduce side effects and increase the effectiveness of treatment. Additionally, the combination arms with trastuzumab, pertuzumab, and tucatinib exploit multiple pathways, aiming to overcome resistance seen with existing therapies and improve outcomes for patients.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Studies have shown that patritumab deruxtecan holds promise for treating breast cancer. Earlier research demonstrated that it helped shrink or eliminate tumors in more than half of the patients. In this trial, one treatment arm will combine patritumab deruxtecan with trastuzumab and pertuzumab. Previous studies have shown this combination to be even more effective, shrinking tumors in 85.1% of patients. Another arm will test the combination of patritumab deruxtecan with trastuzumab and tucatinib, which has shown good results, particularly for patients with cancer that has spread to the brain. These findings suggest that patritumab deruxtecan could be a strong option for treating HER2-positive metastatic breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals with HER2 positive breast cancer that's spread and can't be surgically removed. Participants must have had disease progression after T-DXd treatment, not more than 5 prior anti-HER2 therapies, no history of certain HER2-targeted treatments, controlled HIV or hepatitis if present, and an ECOG performance status of 0 to 1.

Inclusion Criteria

My cancer got worse after treatment with T-DXd.

I have had 5 or fewer previous HER2 treatments for advanced cancer.

I am HBsAg positive but have been on HBV therapy for 4 weeks with an undetectable viral load.

Exclusion Criteria

I have serious heart problems that are not under control.

I have or had lung inflammation needing steroids.

I have never had leptomeningeal disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive patritumab deruxtecan with other anticancer agents in 21-day cycles until disease progression, intolerable toxicity, or investigator decision

Up to approximately 12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Monitoring

Blood samples collected at designated time points to determine pharmacokinetics of patritumab deruxtecan

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Patritumab deruxtecan

Trial Overview The study tests patritumab deruxtecan combined with other anticancer agents in treating advanced HER2 positive breast cancer. It aims to assess the safety, tolerability, and effectiveness in reducing or eliminating cancer.

How Is the Trial Designed?

Group I: Patritumab deruxtecan plus trastuzumab and tucatinib Experimental Treatment 4 Interventions

Participants receive patritumab deruxtecan IV infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks), and tucatinib is administered orally twice daily for each 21-day cycle, until disease progression, intolerable toxicity, or investigator decision.

Group II: Patritumab deruxtecan plus trastuzumab Experimental Treatment 3 Interventions

Participants receive patritumab deruxtecan intravenous (IV) infusion and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.

Group III: Patritumab deruxtecan plus pertuzumab and trastuzumab Experimental Treatment 4 Interventions

Participants receive patritumab deruxtecan IV infusion, pertuzumab IV infusion, and trastuzumab or trastuzumab biosimilar IV infusion on Day 1 of each 21-day cycle (every 3 weeks) until disease progression, intolerable toxicity, or investigator decision.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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

Daiichi Sankyo

Industry Sponsor

Trials

443

Recruited

493,000+

Hiroyuki Okuzawa

Daiichi Sankyo

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Yuki Abe

Daiichi Sankyo

Chief Medical Officer since 2023

MD

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41160818/

Trastuzumab Deruxtecan plus Pertuzumab for HER2- ... Conclusions: Trastuzumab deruxtecan plus pertuzumab led to a significantly lower risk of progression or death than THP when used as first-line ...

2. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/ENHERTU-fam-trastuzumab-deruxtecan-nxki-plus-pertuzumab-reduced-the-risk-of-disease-progression-or-death-by-44-percent-vs-THP-as-1st-line-therapy-in-patients-with-HER2-positive-metastatic-breast-cancer-in-DESTINY-Breast09-Phase-III-trial.html

ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus ... ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab reduced the risk of disease progression or death by 44% vs. THP as 1st-line therapy ...

3. vhio.net vhio.net/2025/10/29/a-new-first-line-therapeutic-combination-shows-greater-efficacy-than-the-standard-treatment-in-metastatic-her2-positive-breast-cancer/

A new first-line therapeutic combination Metastatic Breast ... Confirmed objective response rate (ORR) with the trastuzumab deruxtecan/pertuzumab combination was 85.1%, with a median duration of response ...

4. esmo.org esmo.org/oncology-news/trastuzumab-deruxtecan-plus-pertuzumab-reduce-a-risk-of-progression-or-death-in-first-line-treatment-for-her2-positive-advanced-or-metastatic-breast-cancer

Trastuzumab Deruxtecan Plus Pertuzumab Reduce a Risk ... The incidence of a confirmed response was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with taxane, trastuzumab, and pertuzumab ...

5. onclive.com onclive.com/view/t-dxd-plus-pertuzumab-displays-significant-pfs-benefit-over-soc-therapy-in-frontline-her2-advanced-breast-cancer

T-DXd Plus Pertuzumab Displays Significant PFS Benefit ... Patients who received T-DXd plus pertuzumab (n = 383) achieved a median progression-free survival (PFS) of 40.7 months (95% CI, 36.5-not ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02005

Efficacy and Safety of Trastuzumab Deruxtecan in Patients ... Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625000402

Safety and efficacy of combined trastuzumab-deruxtecan ... The DESTINY Breast 03 trial indicated that treatment with T-DXd resulted in a median progression-free survival of 28.8 months compared with 6.8 months with ...

8. daiichisankyo.us daiichisankyo.us/press-releases/-/article/daiichi-sankyo-continues-to-transform-standards-of-care-for-patients-with-three-landmark-breast-cancer-trials-and-additional-data-across-industry-leading-adc-portfolio-at-esmo

Press Releases Results of these two landmark trials will showcase the potential of ENHERTU® (trastuzumab deruxtecan) to become a foundational treatment in ...