Patritumab Deruxtecan for Non-Small Cell Lung Cancer

Recruiting at 129 trial locations

Overseen By (US sites only) Daiichi Sankyo Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Daiichi Sankyo

Must be taking: EGFR TKIs

Must not be taking: Chronic corticosteroids

Disqualifiers: Small cell disease, Interstitial lung disease, Severe respiratory compromise, Brain metastases, 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: 21 months

277 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called patritumab deruxtecan for patients with advanced lung cancer who have specific genetic mutations and have not responded to other treatments. The drug targets cancer cells specifically and delivers chemotherapy directly to them.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you should continue taking any EGFR TKI until 5 days before starting the trial. There are specific washout periods for other treatments, such as 14 days for certain chemotherapies and 28 days for monoclonal antibodies.

What data supports the effectiveness of the drug Patritumab Deruxtecan for Non-Small Cell Lung Cancer?

Research shows that Patritumab Deruxtecan has been effective in treating non-small cell lung cancer with specific mutations, especially after other treatments have failed. It targets a protein called HER3, which is often found in these cancer cells, and has shown promising results in early studies. ^{1 2 3 4 5}

Is Patritumab Deruxtecan safe for humans?

Patritumab Deruxtecan has been studied in patients with various cancers, including lung and breast cancer, and the safety data from these studies suggest it is generally safe for humans. However, as with any treatment, there may be side effects, and the specific safety profile can vary depending on individual health conditions and other factors. ^{1 2 4 5 6}

What makes the drug Patritumab Deruxtecan unique for treating non-small cell lung cancer?

Patritumab Deruxtecan is unique because it targets the HER3 protein, which is often found in high levels in certain lung cancers, and delivers a cancer-killing agent directly to the cancer cells. This approach is different from standard treatments as it combines a targeted antibody with a chemotherapy drug, potentially offering a new option for patients who have already tried other therapies. ^{1 2 3 5 6}

Research Team

Medical Director

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that has an EGFR mutation and has worsened despite previous treatments including an EGFR TKI and platinum-based chemotherapy. Participants must have good performance status, adequate organ function, no severe respiratory issues or uncontrolled diseases, and not be on high-dose steroids or immunosuppressants.

Inclusion Criteria

I have been treated with a platinum-based chemotherapy.

My recent tests show my organs and bone marrow are working well.

I am 18 years old or older.

Exclusion Criteria

I have not had enough time between my last treatment and the start of this trial.

My cancer diagnosis includes small cell lung cancer, based on previous tissue tests.

I haven't had any other cancer besides this one in the last 3 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive patritumab deruxtecan either as a 5.6 mg/kg fixed dose or an up-titration dose regimen every 3 weeks

21 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

Long-term Follow-up

Participants are monitored for overall survival and other long-term outcomes

Up to 45 months

Treatment Details

Interventions

• Patritumab Deruxtecan

Trial Overview The study tests patritumab deruxtecan's effectiveness in two forms: a fixed dose and an up-titration method. It targets patients whose cancer progressed after at least one prior treatment regimen. The drug aims to inhibit tumor growth by targeting the HER3 protein present in some lung cancers.

Participant Groups

Group I: Study Group 2: Patritumab deruxtecan Up-Titration Experimental Treatment 1 Intervention

Study Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV every 3 weeks (Q3W)

Group II: Study Group 1: Patritumab deruxtecan 5.6 mg/kg Experimental Treatment 1 Intervention

Study Group 1 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W)

Who Is Running the Clinical Trial?

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

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

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

Daiichi Sankyo Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

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) 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]

HER3 is commonly found in EGFR-mutant non-small cell lung cancer (NSCLC), making it an important target for treatment, especially in cases resistant to EGFR tyrosine kinase inhibitors.

Early clinical data suggest that patritumab deruxtecan may be an effective treatment option for patients with previously treated EGFR-mutant NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab Deruxtecan: Paving the Way for EGFR-TKI-Resistant NSCLC. Lim, SM., Kim, CG., Lee, JB., et al.[2022]

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]

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

3. 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]

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

Patritumab Deruxtecan: Paving the Way for EGFR-TKI-Resistant NSCLC. [2022]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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