Patritumab Deruxtecan

Patritumab Deruxtecan (HER3-DXd) is an innovative antibody-drug conjugate being studied in clinical trials for treating several types of cancer, including breast cancer, lung cancer, colorectal cancer, and solid tumors. This article explores the ongoing research into this promising new therapy, its potential benefits, and what patients should know about participating in clinical trials.

Table of Contents

What is Patritumab Deruxtecan?

Patritumab Deruxtecan is an innovative cancer treatment that belongs to a class of drugs called antibody-drug conjugates (ADCs). It’s also known by other names such as HER3-DXd and U3-1402[1]. This medication combines two important components:

  • An antibody that targets a specific protein on cancer cells called HER3 (human epidermal growth factor receptor 3)
  • A powerful anti-cancer drug (deruxtecan) that’s attached to the antibody

This unique combination allows the drug to deliver its cancer-fighting payload directly to tumor cells, potentially increasing its effectiveness while reducing side effects on healthy cells[2].

How Does It Work?

Patritumab Deruxtecan works in a targeted manner:

  1. The antibody part of the drug seeks out and attaches to HER3 proteins on the surface of cancer cells.
  2. Once attached, the cancer cell absorbs the entire drug complex.
  3. Inside the cancer cell, the anti-cancer drug (deruxtecan) is released.
  4. The released drug damages the DNA of the cancer cell, leading to its death.

This mechanism allows for a more precise attack on cancer cells while potentially sparing healthy cells, which may lead to fewer side effects compared to traditional chemotherapy[3].

What Cancers Does It Treat?

Patritumab Deruxtecan is being studied for several types of cancer, including:

  • Breast Cancer: Particularly in patients with HER3-positive metastatic breast cancer (cancer that has spread to other parts of the body)[2].
  • Non-Small Cell Lung Cancer (NSCLC): Especially in patients whose cancer has specific mutations in the EGFR gene and has progressed after other treatments[1].
  • Colorectal Cancer: In patients with advanced or metastatic colorectal cancer who have received at least two prior lines of therapy[4].
  • Other Solid Tumors: Research is ongoing to explore its effectiveness in various other types of solid tumors[3].

Clinical Trials and Research

Patritumab Deruxtecan is currently being studied in several clinical trials to evaluate its safety and effectiveness. Some key studies include:

  • HERTHENA-Lung01: A phase 2 study in patients with previously treated metastatic or locally advanced EGFR-mutated NSCLC[1].
  • HERTHENA-Lung02: A phase 3 study comparing Patritumab Deruxtecan to standard chemotherapy in patients with EGFR-mutated NSCLC that has progressed after other treatments[5].
  • A phase 1/2 study in patients with HER3-positive metastatic breast cancer[2].
  • A phase 2 study in patients with advanced or metastatic colorectal cancer[4].

These trials aim to determine how well the drug works, what doses are most effective, and what side effects may occur.

Administration and Dosage

Patritumab Deruxtecan is typically administered as an intravenous (IV) infusion. The most common dosage being studied is 5.6 mg/kg given every 3 weeks[1]. However, some studies are exploring different dosing regimens, including:

  • Fixed dosing at 5.6 mg/kg every 3 weeks
  • Up-titration dosing, starting at a lower dose and gradually increasing

The exact dosage and schedule may vary depending on the type of cancer being treated and individual patient factors. Always follow your doctor’s instructions regarding dosage and administration[5].

Potential Side Effects

Like all medications, Patritumab Deruxtecan can cause side effects. Some of the potential side effects reported in clinical trials include:

  • Diarrhea
  • Nausea and vomiting
  • Fatigue
  • Decreased appetite
  • Low blood cell counts
  • Interstitial lung disease (a rare but serious lung condition)

It’s important to note that not everyone experiences these side effects, and your healthcare team will monitor you closely during treatment. Always report any new or worsening symptoms to your doctor[6].

Future Prospects

Patritumab Deruxtecan shows promise in treating various types of cancer, particularly in patients who have progressed on other treatments. Ongoing research is exploring its potential in different cancer types and treatment combinations. For example:

  • Its use in combination with other cancer drugs, such as olaparib in breast cancer[7].
  • Its effectiveness in treating brain metastases (cancer that has spread to the brain)[6].
  • Its potential as a neoadjuvant treatment (given before surgery) in breast cancer[8].

As research continues, we may learn more about how to use this drug most effectively and in which patients it works best. If you’re interested in learning more about Patritumab Deruxtecan or participating in a clinical trial, talk to your oncologist about whether this treatment might be appropriate for you.

Aspect Details
Drug Name Patritumab Deruxtecan (HER3-DXd, U3-1402)
Drug Type Antibody-drug conjugate targeting HER3
Cancer Types Studied Breast cancer, Non-small cell lung cancer, Colorectal cancer, Solid tumors
Administration Intravenous infusion, typically every 3 weeks
Common Dosage 5.6 mg/kg (may vary by trial)
Key Outcomes Measured Objective response rate, Duration of response, Progression-free survival
Safety Monitoring Adverse events, Lab abnormalities, Special focus on interstitial lung disease
Combination Studies With chemotherapy, endocrine therapy, and targeted therapies like olaparib
Biomarker Analysis HER3 expression levels, ERBB3 mRNA expression
Quality of Life Assessments Using EORTC QLQ-BR45 and QLQ-C30 questionnaires

Ongoing Clinical Trials on Patritumab Deruxtecan

  • Evaluation of Safety and Efficacy of MK-2870 and Paclitaxel in Second-Line Treatment of Advanced/Metastatic Gastroesophageal Adenocarcinoma

    Recruiting

    1 1 1 1
    France Germany Italy Norway
  • Study of patritumab deruxtecan versus drug combination in patients with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer

    Recruiting

    3 1 1 1
    France Germany Greece Hungary Italy Poland +1
  • A study of MK-1084 and a drug combination for patients with advanced or metastatic non-small cell lung cancer with KRAS G12C mutations.

    Recruiting

    1 1 1 1
    Germany Greece Hungary Italy Poland Spain
  • Study on the Safety and Effectiveness of Patritumab Deruxtecan for Children with Relapsed or Refractory Hepatoblastoma and Rhabdomyosarcoma

    Recruiting

    1 1 1 1
    Belgium Czechia Denmark France Germany Greece +6
  • Study of Patritumab Deruxtecan and Pembrolizumab for Patients with High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive Breast Cancer

    Recruiting

    2 1 1 1
    Spain
  • Study on MK-2870, Pembrolizumab, and Chemotherapy for Patients with Advanced Gastroesophageal Cancer

    Recruiting

    1 1 1 1
    Investigated diseases:
    France Germany Italy Norway
  • Study on the Safety and Effectiveness of Patritumab Deruxtecan for Patients with Colorectal, Biliary Tract, and Liver Cancer

    Recruiting

    1 1 1 1
    Investigated drugs:
    France Italy Spain
  • Study of Patritumab Deruxtecan for Patients with Advanced or Metastatic Solid Tumors

    Recruiting

    2 1 1
    Investigated drugs:
    Belgium France Germany Hungary Italy The Netherlands +2
  • Study on Patritumab Deruxtecan and Zirconium (89Zr) Patritumab Deruxtecan for Patients with Advanced EGFR Mutation Positive Lung Cancer

    Recruiting

    2 1 1
    Investigated diseases:
    The Netherlands
  • Evaluation of Pembrolizumab, Patritumab Deruxtecan, and Drug Combinations in Stage IV Non-Small Cell Lung Cancer: A Phase 2 Umbrella Study

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Greece Hungary Italy Poland Spain

Glossary

  • Antibody-drug conjugate (ADC): A type of targeted cancer therapy that combines a monoclonal antibody with a potent chemotherapy drug. The antibody helps deliver the chemotherapy directly to cancer cells.
  • HER3: Human Epidermal Growth Factor Receptor 3, a protein found on the surface of some cancer cells that can promote tumor growth when activated.
  • Metastatic cancer: Cancer that has spread from its original site to other parts of the body.
  • Objective response rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives without the cancer getting worse.
  • Interstitial lung disease (ILD): A group of disorders that cause inflammation and scarring in the lungs, which can be a rare but serious side effect of some cancer treatments.
  • RECIST criteria: Response Evaluation Criteria in Solid Tumors, a standard way to measure how well a cancer patient responds to treatment.
  • Neoadjuvant therapy: Treatment given before the main treatment, usually to shrink a tumor before surgery.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and excreted.
  • Anti-drug antibody (ADA): Antibodies produced by the immune system against a therapeutic drug, which can potentially reduce its effectiveness.

References

  1. https://clinicaltrials.gov/study/NCT04619004
  2. https://clinicaltrials.gov/study/NCT02980341
  3. https://clinicaltrials.gov/study/NCT06383884
  4. https://clinicaltrials.gov/study/NCT04479436
  5. https://clinicaltrials.eu/trial/study-comparing-patritumab-deruxtecan-and-platinum-based-chemotherapy-for-patients-with-advanced-egfr-mutated-non-small-cell-lung-cancer-after-egfr-therapy-failure/
  6. https://clinicaltrials.gov/study/NCT05620914
  7. https://clinicaltrials.gov/study/NCT06298084
  8. https://clinicaltrials.eu/trial/study-of-patritumab-deruxtecan-with-or-without-endocrine-therapy-for-high-risk-hr-her2-early-breast-cancer-in-untreated-patients/