HER3-DXd for Cancer

Recruiting at 98 trial locations

Overseen By Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Daiichi Sankyo, Inc.

Must not be taking: Chronic corticosteroids, Anti-HER3 ADCs

Disqualifiers: HER2-positive gastric cancer, Nasopharyngeal cancer, Mucosal melanoma, ILD, 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: 3

Duration: 27 months

740 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called HER3-DXd for individuals with certain advanced or metastatic cancers that cannot be removed by surgery or cured with radiation. The goal is to evaluate the effectiveness of HER3-DXd when used alone for treating various cancers, including melanoma, head and neck cancer, gastric cancer, ovarian cancer, and others. Individuals who have tried other treatments but still experience cancer progression may be eligible. Those with one of these cancers, for whom previous treatments have been ineffective, might find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on chronic systemic corticosteroids over 10 mg of prednisone or similar medications. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that HER3-DXd is likely to be safe for humans?

Research shows that HER3-DXd has undergone safety testing in patients with various types of cancer. In earlier studies, most patients tolerated HER3-DXd well. However, some side effects, such as low blood counts, nausea, and tiredness, have been reported. These side effects are common with many cancer treatments.

Since this trial is in a middle stage, research continues to confirm its safety. This stage indicates some early evidence of safety, but more information is needed. Participants in this trial will help gather more details about how well people tolerate this treatment for different cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for various advanced cancers, such as chemotherapy or targeted therapies like EGFR inhibitors, HER3-DXd acts uniquely by targeting the HER3 receptor, which is often overexpressed in certain cancers and linked to tumor growth and survival. HER3-DXd is an antibody-drug conjugate, combining an antibody that specifically targets HER3 with a potent chemotherapy agent, delivering the drug directly to cancer cells while sparing healthy cells. Researchers are excited about HER3-DXd because this targeted approach has the potential to improve effectiveness while reducing side effects, offering new hope for patients with difficult-to-treat cancers.

What evidence suggests that HER3-DXd might be an effective treatment for cancer?

Research shows that HER3-DXd, administered as monotherapy in this trial, is a promising treatment for various advanced cancers. Early studies have found that HER3-DXd targets the HER3 protein, present in many cancer cells, which may help slow or stop tumor growth. Initial results suggest that patients with different solid tumors, such as melanoma, lung cancer, and breast cancer, have responded well to this treatment. Scientists study HER3-DXd because it could offer a new option for people whose cancers do not respond well to current treatments. While more research is needed, the findings so far are encouraging. ^{1 2 3 4 5}

Who Is on the Research Team?

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including specific types of melanoma, head and neck cancers, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma and prostate cancer. Participants must have experienced disease progression after prior treatments.

Inclusion Criteria

My cancer has worsened despite treatment with a PBC regimen and possibly anti-PD-1 therapy.

My cancer is in the stomach or where the stomach meets the esophagus.

My melanoma worsened despite BRAF/MEK inhibitor treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HER3-DXd monotherapy 5.6 mg/kg every 3 weeks

27 months

Every 3 weeks (in-person)

Pharmacokinetic Assessment

Pharmacokinetic parameters such as AUClast, AUCtau, Cmax, Tmax, and Ctrough are assessed

Cycles 1-4, 6, 8 (each cycle is 21 days)

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HER3-DXd

Trial Overview The study tests HER3-DXd monotherapy in patients with various solid tumors. It focuses on those who've had previous treatments but their disease has progressed. The goal is to see how effective this new therapy is on its own.

How Is the Trial Designed?

Group I: HER3-DXd Monotherapy Experimental Treatment 1 Intervention

Participants with locally advanced unresectable or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, prostate cancer, second-line gastric cancer, lung cancer, and breast cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).

Who Is Running the Clinical Trial?

Daiichi Sankyo, Inc.

Lead Sponsor

Trials

390

Recruited

442,000+

Yuki Abe

Daiichi Sankyo, Inc.

Chief Medical Officer since 2022

MD

Hiroyuki Okuzawa

Daiichi Sankyo, Inc.

Chief Executive Officer

Degree in Social Sciences from Hitotsubashi University

Daiichi Sankyo

Lead 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

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

Published Research Related to This Trial

Patritumab deruxtecan (HER3-DXd) is a promising new treatment for EGFR-mutated non-small cell lung cancer (NSCLC) that has progressed after standard therapies, showing antitumor activity and a tolerable safety profile in an ongoing phase I study.

HER3-DXd targets the HER3 receptor, which is often overexpressed in EGFR-mutated NSCLC, and is currently being further evaluated in a global phase II trial (HERTHENA-Lung01) to confirm its efficacy in patients who have already received other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. Yu, HA., Yang, JC., Hayashi, H., et al.[2023]

Patritumab deruxtecan, an antibody-drug conjugate targeting HER3, was analyzed using pharmacokinetics data from 425 patients with solid tumors, showing a well-defined clearance and distribution profile that supports its use in clinical settings.

The study found that factors like weight, albumin levels, sex, and tumor type had mild effects on drug exposure, indicating that no significant dose adjustments are needed for different patient subpopulations in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors. Lu, Y., Shimizu, S., Sawamura, R., et al.[2023]

In a study of 77 patients with early breast cancer, a single dose of patritumab deruxtecan (HER3-DXd) significantly increased the CelTIL score, indicating enhanced immune infiltration and a shift towards a less proliferative tumor phenotype.

The treatment showed a clinical response rate of 45% among patients, with most experiencing manageable side effects, suggesting HER3-DXd has a tolerable safety profile and warrants further investigation in early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. Oliveira, M., Falato, C., Cejalvo, JM., et al.[2023]

The study is investigating the HER3-directed antibody drug conjugate patritumab deruxtecan (HER3-DXd) in patients with HR-positive/HER2-negative early breast cancer, focusing on its biological effects after a single dose.

The primary endpoint is to assess the CelTIL score, which will help evaluate the drug's impact on the tumor microenvironment and resistance mechanisms, providing valuable insights into its efficacy and potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer. Pascual, T., Oliveira, M., Ciruelos, E., et al.[2021]

In a phase II study involving 225 patients with advanced EGFR-mutated non-small-cell lung cancer, HER3-DXd demonstrated a confirmed objective response rate of 29.8%, indicating meaningful efficacy after prior treatments with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy.

The safety profile of HER3-DXd was manageable and tolerable, with median overall survival of 11.9 months and notable efficacy in patients with nonirradiated brain metastases, showing a CNS objective response rate of 33.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. Yu, HA., Goto, Y., Hayashi, H., et al.[2023]

Patritumab deruxtecan (HER3-DXd) showed promising efficacy in treating advanced breast cancer, with objective response rates of 30.1% in hormone receptor-positive/HER2-negative patients and 42.9% in HER2-positive patients, indicating its potential as a treatment option for various breast cancer subtypes.

The safety profile of HER3-DXd was manageable, with common treatment-emergent adverse events including gastrointestinal and hematologic toxicities; however, 71.4% of patients experienced grade ≥3 adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial. Krop, IE., Masuda, N., Mukohara, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06172478

NCT06172478 | A Study of HER3-DXd in Subjects With ... This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12536771/

HERTHENA-PanTumor01: a phase II study of patritumab ... HERTHENA-PanTumor01 (NCT06172478) is an ongoing global, multicohort, signal-seeking, phase II trial assessing the efficacy and safety of HER3- ...

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0963.html

HERTHENA-PanTumor01 (U31402-277): A phase 2, ... This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors.

4. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_15322.a-study-of-her3-dxd-in-subjects-with-locally-advanced-or-metastatic-solid-tumors.html

A Study of HER3-DXd in Subjects With Locally Advanced ... This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced or metastatic solid tumors.

5. roswellpark.org roswellpark.org/clinical-trials/list/5512

A Study of HER3-DXd in Subjects With Locally Advanced or ... This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced unresectable or metastatic solid tumors.