Patritumab Deruxtecan + Pembrolizumab for Breast Cancer

Recruiting at 17 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-PD-L2, Anti-HER3

Disqualifiers: Cardiovascular disease, Corneal disease, 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: 9

372 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for certain types of breast cancer, specifically triple-negative and hormone receptor low-positive/human epidermal growth factor receptor-2 negative breast cancer. It tests whether a combination of patritumab deruxtecan (an experimental treatment), pembrolizumab (an immunotherapy drug), and chemotherapy before surgery can reduce cancer cells more effectively than pembrolizumab and chemotherapy alone. Researchers aim to determine if participants can safely tolerate these treatments and if fewer cancer cells remain during surgery. This trial may suit those with locally advanced, non-metastatic breast cancer who meet specific medical criteria related to the cancer's characteristics. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether 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?

Previous studies found that patritumab deruxtecan has a manageable safety profile. Even in patients with many prior treatments, side effects were present but controllable. Overall, the treatment was generally well-tolerated over a long period.

Research has shown that pembrolizumab can cause some immune-related side effects. About 35% of patients experienced these, with 13% having severe reactions. When combined with chemotherapy, the most common side effects were nausea, tiredness, and loss of appetite. While serious side effects can occur, they are usually manageable with medical help.

Both treatments have been tested in many patients and are generally well-tolerated. However, side effects can occur, and the trial team will monitor participants closely. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Patritumab Deruxtecan in combination with Pembrolizumab for breast cancer because it offers a unique approach compared to standard treatments like chemotherapy and hormone therapy. Patritumab Deruxtecan is an antibody-drug conjugate, meaning it can deliver cancer-killing agents directly to tumor cells, potentially increasing effectiveness and reducing side effects. Pembrolizumab, on the other hand, is an immunotherapy that helps the immune system recognize and attack cancer cells. This combination could provide a powerful one-two punch against breast cancer by both directly targeting cancer cells and boosting the body's natural defenses.

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

Research shows that patritumab deruxtecan has promising results for certain breast cancers. In advanced cases, it helped shrink tumors in over half of the patients. This trial will administer patritumab deruxtecan in combination with pembrolizumab to some participants. When combined with chemotherapy, pembrolizumab has improved survival rates for triple-negative breast cancer (TNBC). Studies have found that adding pembrolizumab to chemotherapy results in longer survival compared to chemotherapy alone. This trial will explore the effects of both treatments, either together or in sequence, to aid patients with TNBC and hormone receptor-low breast cancers. ^{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 people with early-stage, high-risk triple-negative or hormone receptor-low positive/HER-2 negative breast cancer that hasn't spread. Participants should be relatively healthy and active (ECOG 0-1), have a good heart function (LVEF ≥50%), and no history of certain infections or treatments like anti-PD-1/L1/L2 agents.

Inclusion Criteria

Participants with history of HCV infection must have undetectable HCV viral load

Has LVEF of ≥50% or ≥LLN as assessed by ECHO or MUGA scan

My breast cancer has not spread beyond nearby areas.

Exclusion Criteria

Has concurrent active HBV and HCV infection

I have received treatment for my current breast cancer diagnosis.

I have been treated with anti-HER3 antibody or ADC with exatecan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive neoadjuvant pembrolizumab and other agents for 12 weeks

12 weeks

Every 3 weeks (in-person)

Surgery

Participants undergo surgery for breast cancer 3 to 6 weeks after last dose of neoadjuvant treatment

3-6 weeks after treatment

Adjuvant Treatment

Participants receive adjuvant pembrolizumab and additional treatment of physician's choice for approximately 30 weeks

30 weeks

Every 6 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• Patritumab Deruxtecan
• Pembrolizumab

Trial Overview The study tests if combining patritumab deruxtecan and pembrolizumab with chemotherapy before surgery can reduce cancer cells more effectively than just pembrolizumab and chemo. It also looks at the safety and tolerability of these treatments.

How Is the Trial Designed?

Group I: Part 2, B: Pembrolizumab + paclitaxel + carboplatin → Pembrolizumab + patritumab deruxtecan Experimental Treatment 9 Interventions

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus patritumab deruxtecan (dose to be determined in part 1) via IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for \~30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W or Q2W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W or Q2W for 4 doses.

Group II: Part 2, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin Experimental Treatment 9 Interventions

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion every Q3W plus patritumab deruxtecan (dose to be determined in part 1) IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min IV infusion QW for 12 weeks. At 3-6 weeks after last dose of neoadjuvant treatment, participants undergo surgery for breast cancer. After surgery, participants receive adjuvant pembrolizumab 400 mg IV every 6 weeks (Q6W) for \~30 weeks. Additional adjuvant treatment of physician's choice (TPC) may be given to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline BRCA mutation \[gBRCAm\] only), capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles or doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV Q3W or every 2 weeks (Q2W) and cyclophosphamide 600 mg/m\^2 IV Q3W or Q2W for 4 doses.

Group III: Part 1, A: Pembrolizimab + patritumab deruxtecan → Pembrolizumab + paclitaxel + carboplatin Experimental Treatment 4 Interventions

In Part 1, participants receive neoadjuvant pembrolizumab 200 mg via intravenous (IV) infusion every 3 weeks (Q3W) plus patritumab deruxtecan via IV infusion Q3W for 12 weeks, followed by pembrolizumab 200 mg via IV infusion Q3W plus paclitaxel 80 mg/m\^2 via IV infusion every week (QW) and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer.

Group IV: Part 2, C: Pembro + paclitaxel + carboplatin→ Pembro + doxorubicin (or epirubicin) +cyclophosphamide Active Control 8 Interventions

In Part 2, participants receive neoadjuvant pembrolizumab 200 mg IV infusion Q3W plus paclitaxel 80 mg/m\^2 IV infusion QW and carboplatin AUC1.5 mg/ml/min via IV infusion QW for 12 weeks, followed by pembrolizumab 200 mg IV infusion Q3W plus doxorubicin 60mg/m\^2 (or epirubicin 90 mg/m\^2) IV infusion Q3W and cyclophosphamide 600 mg/m\^2 IV infusion Q3W for 12 weeks. At 3 to 6 weeks after last dose of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will receive adjuvant pembrolizumab 400 mg IV infusion Q6W for approximately 30 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options include olaparib 300 mg oral BID for 1 year (participants with gBRCAm only) or capecitabine 1000-1250 mg/m\^2 oral BID days 1-14 and 22-35 Q6W for 4 six-week cycles.

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

Published Research Related to This Trial

In a phase Ib study involving 64 patients with Stage IV non-small cell lung cancer (NSCLC), the combination of necitumumab and pembrolizumab showed a confirmed overall response rate of 23.4%, indicating modest efficacy in this patient population.

The treatment was well-tolerated, with no dose-limiting toxicities reported, and the safety profile was consistent with typical effects of epidermal growth factor receptor inhibitors and immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of necitumumab and pembrolizumab combination therapy in patients with Stage IV non-small cell lung cancer. Besse, B., Garrido, P., Cortot, AB., et al.[2021]

Pembrolizumab, when combined with chemotherapy, significantly improves pathological complete response (pCR) and event-free survival (EFS) in patients with high-risk, early-stage triple-negative breast cancer, as shown in the KEYNOTE-522 trial with 123 EFS events in the pembrolizumab group compared to 93 in the control group.

Despite 44% of patients experiencing immune-related adverse reactions, the benefits of pembrolizumab, including a 7.5% absolute improvement in pCR rates, support its use as an effective neoadjuvant and adjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Neoadjuvant and Adjuvant Treatment of Patients with High-Risk Early-Stage Triple-Negative Breast Cancer. Shah, M., Osgood, CL., Amatya, AK., et al.[2023]

In a phase Ib/II trial, the combination of the PD-1 inhibitor pembrolizumab with trastuzumab demonstrated clinical benefits for patients with advanced HER2-positive breast cancer who had become resistant to trastuzumab.

The study identified tumor-infiltrating lymphocyte levels as a potential biomarker, which could help predict how well patients might respond to this combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role for Immune Therapy in Advanced Breast Cancer. [2019]

In a study of 145 patients with PD-L1 strongly positive non-small-cell lung cancer (NSCLC), those with higher PD-L1 expression (≥ 75%) experienced better treatment outcomes with pembrolizumab, showing a higher objective response rate (51% vs. 33%) and longer progression-free survival (13.9 months vs. 5.2 months).

Patients with liver metastasis had significantly poorer responses to pembrolizumab, with an objective response rate of only 20% compared to 47% in those without liver metastasis, indicating that both PD-L1 expression and liver metastasis are important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC. Takeyasu, Y., Yoshida, T., Shibaki, R., et al.[2021]

In a phase II study involving 22 patients with BRCA1/2-related metastatic breast cancer, the combination of pembrolizumab and carboplatin showed an overall response rate (ORR) of 43% and a disease control rate (DCR) of 76%, indicating some level of efficacy, particularly in luminal tumors.

Despite the promising results, the study did not meet its primary aim of achieving an ORR of 70%, leading to its termination; however, the safety profile was acceptable with only 22.7% of patients experiencing grade ≥3 adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer (PEMBRACA). Cortesi, L., Venturelli, M., Cortesi, G., et al.[2023]

In a meta-analysis of 11 clinical trials involving 3713 patients, the overall incidence of fatal adverse events (FAEs) associated with pembrolizumab was found to be 1.2%, indicating a relatively low risk of severe complications from this immune checkpoint inhibitor.

The incidence of FAEs varied significantly by tumor type, with breast cancer patients experiencing a higher risk (3.1%) compared to melanoma patients (0.2%), and the combination of pembrolizumab with chemotherapy resulted in a much higher incidence of FAEs (7.0%) compared to pembrolizumab alone (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. Sher, AF., Golshani, GM., Wu, S.[2020]

A review of 29 articles identified specific dermatological adverse events (AEs) associated with various immunotherapy combinations, highlighting that combinations like nivolumab/ipilimumab and lenvatinib/pembrolizumab had the highest incidence of rash.

Understanding these dermatological AEs, such as pruritus and alopecia, is crucial for optimizing treatment plans and improving patient monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermatological adverse events associated with immune checkpoint inhibitor-based combinations of anticancer therapies: a systematic review. Salloum, A., Habre, M., Chebl, JA., et al.[2022]

In a multicenter retrospective analysis of early triple-negative breast cancer (eTNBC) patients treated with pembrolizumab and chemotherapy, the incidence of immune-related adverse events (irAEs) was found to be 63.9%, with 20% of patients experiencing severe (grade 3 or higher) irAEs.

The study reported a pathological complete response (pCR) rate of 57.1%, with a significant correlation between the occurrence of irAEs and higher pCR rates (72.2% vs. 30.8%), indicating that while irAEs are common, they may be associated with better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer. Marhold, M., Udovica, S., Halstead, A., et al.[2023]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor used for treating non-small cell lung cancer, is generally well tolerated, but can lead to rare immune-mediated adverse effects such as pleuropericarditis, as seen in a case involving a 64-year-old female patient.

The patient was effectively treated with colchicine, furosemide, and methylprednisolone, leading to symptom improvement and a decision to discontinue pembrolizumab, after which she remained asymptomatic for six months, highlighting the importance of recognizing and managing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unusual case of checkpoint-inhibitor-induced pleuropericarditis. Suarez, ZK., Finke, AC., Hospedales, E., et al.[2023]

Checkpoint inhibitors like nivolumab and pembrolizumab can lead to autoimmune side effects, including immune thrombocytopenia, which was observed in a patient with metastatic melanoma shortly after starting treatment.

Unlike chemotherapy-induced cytopenia, which is caused by bone marrow toxicity, thrombocytopenia from checkpoint inhibitors is primarily autoimmune in nature, highlighting the need for careful monitoring and immune testing during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with PD1-Blocking Agents for Metastatic Melanoma. Pföhler, C., Eichler, H., Burgard, B., et al.[2022]

Citations

1. nature.com nature.com/articles/s41591-025-03885-3

Patritumab deruxtecan in HR+HER2− advanced breast ... Trastuzumab deruxtecan (T-DXd) has substantiallyimproved survival outcomes in patients with HER2 (also known as ERBB2)-expressing breast cancer ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00882

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal ... Most patients (80.0%), across clinical subtypes, experienced a reduction in the best percentage change in tumor size from baseline (Fig 2). In ...

3. daiichisankyo.us daiichisankyo.us/press-releases/-/article/herthena-breast04-phase-3-trial-of-patritumab-deruxtecan-initiated-in-patients-with-metastatic-hormone-receptor-positive-her2-negative-breast-cancer-previously-treated-with-endocrine-therapy

HERTHENA-Breast04 Phase 3 Trial of Patritumab ... Patients with HR positive, HER2 negative metastatic breast cancer experience poor outcomes if they progress following initial treatment, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37801674/

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal ... Conclusion: HER3-DXd demonstrated a manageable safety profile and durable efficacy in heavily pretreated patients across clinical subtypes.

5. onclive.com onclive.com/view/patritumab-deruxtecan-demonstrates-meaningful-activity-in-hr-her2-advanced-breast-cancer

Patritumab Deruxtecan Demonstrates Meaningful Activity ... Patritumab deruxtecan showed a 53.5% objective response rate and 62.6% clinical benefit rate in advanced breast cancer patients post-CDK4/6 ...

6. merck.com merck.com/news/herthena-breast04-phase-3-trial-of-patritumab-deruxtecan-initiated-in-patients-with-metastatic-hormone-receptor-positive-her2-negative-breast-cancer-previously-treated-with-endocrine-therapy/

HERTHENA-Breast04 Phase 3 Trial of Patritumab ... HERTHENA-Breast04 is an open-label, randomized, phase 3 trial evaluating the safety and efficacy of patritumab deruxtecan (5.6 mg/kg) ...

7. daiichisankyo.com daiichisankyo.com/files/news/pressrelease/pdf/202206/20220603_E.pdf

breast cancer An ORR of 42.9% (95% CI: 17.7-71.1) was observed with patritumab deruxtecan in the cohort of 14 patients with HER3 high, HER2 positive metastatic breast cancer ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40908353/

Patritumab deruxtecan in HR+HER2- advanced breast ... Here we report the results of ICARUS-BREAST01, a phase 2 study evaluating efficacy, safety and biomarkers of response and resistance to ...