Patritumab Deruxtecan for Gastrointestinal Cancer

Recruiting at 78 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: Interstitial lung disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to approximately 45 months

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called patritumab deruxtecan, an experimental drug, to determine its effectiveness in treating certain advanced gastrointestinal (GI) cancers. Researchers aim to assess the treatment's safety and how well participants tolerate it. They also seek to observe whether the cancer shrinks or disappears in response to the treatment. Individuals with advanced colorectal, biliary tract, liver, or gastroesophageal cancers who have previously tried other treatments and recovered from any side effects might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that patritumab deruxtecan is likely to be safe for humans?

Research has shown that patritumab deruxtecan is generally well-tolerated by patients. One study found its safety profile in people with gastrointestinal cancer similar to that in those with metastatic breast cancer. Common side effects, usually manageable, include nausea, tiredness, and low blood cell counts. Serious side effects can occur but are less common. As this trial is in the early stages, the researchers are still collecting safety information. Participants are closely monitored for any side effects during the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Patritumab deruxtecan is unique because it is a targeted therapy that combines an antibody with a chemotherapy drug to specifically attack cancer cells. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, patritumab deruxtecan targets the HER3 protein that is often overexpressed in gastrointestinal cancers. This targeted approach aims to deliver chemotherapy directly to the cancer cells, potentially reducing side effects and increasing effectiveness. Researchers are excited about this treatment because it represents a new way to precisely target cancer cells, offering hope for better outcomes with fewer side effects than standard chemotherapy options.

What evidence suggests that patritumab deruxtecan might be an effective treatment for gastrointestinal cancer?

Research has shown that patritumab deruxtecan, which participants in this trial will receive, may help treat certain types of gastrointestinal cancers. In earlier studies, this treatment proved effective in patients whose cancers did not respond well to other treatments. For instance, one study that gradually increased the dosage found that some patients experienced a noticeable decrease in tumor size. This treatment targets a specific protein on cancer cells, allowing the drug to go directly to the tumor. Overall, early results suggest that patritumab deruxtecan could be useful in managing advanced gastrointestinal cancers, but more research is needed to confirm these findings. ^{1 2 3 6 7}

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 advanced gastrointestinal cancers that have spread, including colorectal cancer, biliary tract cancer (BTC), and hepatocellular carcinoma (HCC) not treatable by local therapy. Participants should have had prior treatment and recovered from any previous treatment side effects.

Inclusion Criteria

I have advanced colorectal, biliary tract, or liver cancer that cannot be surgically removed.

I have undergone treatment for my cancer before.

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

I have severe breathing problems due to lung illness.

I have a serious eye condition affecting my cornea.

I have or had lung inflammation that needed steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

Up to approximately 45 months

1 visit every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Patritumab Deruxtecan

Trial Overview The study is testing patritumab deruxtecan to see if it's safe and tolerable, and how effective it is in shrinking or eliminating certain advanced GI cancers. Researchers will monitor participants' responses to the drug.

How Is the Trial Designed?

Group I: Patritumab deruxtecan Experimental Treatment 1 Intervention

Participants receive patritumab deruxtecan intravenous (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

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS321

Phase 1/2 study of the HER3-directed antibody-drug ... This nonrandomized, open-label, phase 1/2 study (NCT06596694) will examine the safety and efficacy of patritumab deruxtecan in select gastrointestinal cancers.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06596694

NCT06596694 | Study of Patritumab Deruxtecan in ... Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain gastrointestinal (GI) cancers. The GI cancers being studied are advanced (the ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9401524/

Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in ... In a phase I dose escalation/expansion study, use of the HER3-DXd antibody drug conjugate showed clinical activity in EGFR TKI-resistant, EGFR-mutant ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT322519

An open-label, phase II study of patritumab deruxtecan ... An open-label, phase II study of patritumab deruxtecan (HER3-DXd, U3-1402) in patients (pts) with previously treated advanced/metastatic colorectal cancer (CRC) ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(20)42377-4/fulltext

LBA62 Efficacy and safety of patritumab deruxtecan (U3 ... As of 30 April 2020, 57 pts from dose escalation and dose expansion were treated at the 5.6 mg/kg dose, and 56 pts were evaluable for response. Among 28 pts ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06596694

NCT06596694 | Study of Patritumab Deruxtecan in ... The goals of this study are to learn: About the safety and how well people tolerate of patritumab deruxtecan; How many people have the cancer respond (get ...

7. datasourcebydaiichisankyo.com datasourcebydaiichisankyo.com/clinical-trials/-/view/study/NCT06596694

Clinical Trials A Phase 1/2 Study to Evaluate the Safety and Efficacy of Patritumab Deruxtecan in Gastrointestinal Cancers. Inclusion Criteria. The main ...