Patritumab Deruxtecan for Gastrointestinal Cancer

Recruiting at 55 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

130 Participants Needed

Trial Summary

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.

What data supports the idea that Patritumab Deruxtecan for Gastrointestinal Cancer is an effective treatment?

The available research does not provide specific data on the effectiveness of Patritumab Deruxtecan for Gastrointestinal Cancer. However, studies have shown that it has promising results in treating other cancers, such as lung and breast cancer. For example, in lung cancer, it showed promising antitumor activity and a tolerable safety profile in patients with specific mutations. This suggests potential effectiveness in other cancers, but more research is needed for gastrointestinal cancer specifically. ^{1 2 3 4 5}

What safety data is available for Patritumab Deruxtecan?

Safety data for Patritumab Deruxtecan, also known as HER3-DXd, has been evaluated in multiple studies across different cancer types. In the HERTHENA-Lung01 Phase II trial, the safety of HER3-DXd was assessed in patients with EGFR-mutated non-small-cell lung cancer. Additionally, population pharmacokinetics analysis was conducted with data from patients with HER3-expressing solid tumors, including breast, lung, and colorectal cancer, to inform dose selection and evaluate safety. The drug has also been studied in metastatic breast cancer and early breast cancer, with safety being a key component of these trials. Overall, these studies provide a foundation of safety data for Patritumab Deruxtecan in various cancer settings. ^{1 2 3 5 6}

Is the drug Patritumab Deruxtecan a promising treatment for gastrointestinal cancer?

Patritumab Deruxtecan is a promising drug because it targets a specific protein called HER3, which is involved in cancer growth. It has shown effectiveness in treating various cancers, including breast and lung cancer, by delivering a powerful cancer-fighting agent directly to the cancer cells. This targeted approach can help improve treatment outcomes. ^{1 2 3 5 7}

What is the purpose of this trial?

Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain gastrointestinal (GI) cancers. The GI cancers being studied are advanced (the cancer has spread to other parts of the body). 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 smaller or go away) to treatment

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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 or had lung inflammation that needed steroids.

I have severe breathing problems due to lung illness.

I have a serious eye condition affecting my cornea.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2023]

2. United States 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Patritumab Deruxtecan in Patients With Solid Tumors. [2023]

4. England pubmed.ncbi.nlm.nih.gov

HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. [2023]

5. England 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. [2023]

6. Switzerland 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Patritumab Deruxtecan Is Efficacious in EGFR-Mutant Non-Small Cell Lung Cancer. [2023]