Patritumab Deruxtecan for Non-Small Cell Lung Cancer

Not currently recruiting at 152 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, patritumab deruxtecan (an experimental drug), for individuals with non-small cell lung cancer (NSCLC) that has advanced or metastasized. The focus is on patients with specific genetic changes in the EGFR gene who have already tried treatments like EGFR-targeted drugs and chemotherapy. Participants will receive the new treatment to evaluate its effectiveness against their cancer. This trial is suitable for those with specific EGFR mutations (exon 19 deletion or L858R) who have experienced cancer progression after previous treatments. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

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

Research has shown that patritumab deruxtecan has safety data from studies involving patients with non-small cell lung cancer. One study found that about 10.6% of patients developed interstitial lung disease, a condition affecting the lungs. These cases were mild to moderate, indicating they were not severe but still noteworthy. Other studies have examined the treatment's safety and found it to be generally well-tolerated. While some risks exist, most patients have managed them well. Anyone considering joining a trial should discuss all possible side effects with their doctor to understand what these findings might mean for them. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-small cell lung cancer?

Patritumab deruxtecan is unique because it targets non-small cell lung cancer (NSCLC) with a specific EGFR-activating mutation, which is different from the traditional chemotherapy and tyrosine kinase inhibitors typically used for this condition. This treatment combines an antibody with a potent anti-cancer drug, ensuring precise delivery directly to cancer cells, minimizing damage to healthy cells. Researchers are excited because this targeted approach could lead to more effective treatment outcomes with fewer side effects, offering hope for patients whose cancer has become resistant to other therapies.

What evidence suggests that patritumab deruxtecan could be an effective treatment for non-small cell lung cancer?

Research has shown that patritumab deruxtecan may help treat non-small cell lung cancer (NSCLC) with EGFR mutations. In this trial, participants will be randomized into two groups: Study Group 1 will receive patritumab deruxtecan at a dose of 5.6 mg/kg, while Study Group 2 will receive an up-titration of the drug. Studies have found that patritumab deruxtecan can significantly extend the time patients live without their cancer worsening. Previous results in patients with EGFR-mutated NSCLC, who have already tried other treatments, were positive. This treatment targets a specific protein on cancer cells, delivering cancer-fighting agents directly to them. Overall, evidence supports its potential effectiveness for patients who have already undergone other therapies. ^{1 2 4 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

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 fully active or can carry out light work.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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) 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 (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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40554742/

MK-1022) in Non-Small Cell Lung Cancer After Platinum- ... The previously reported efficacy and safety of HER3-DXd in heavily pretreated patients with EGFR-mutated NSCLC are also observed in those ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02744

Patritumab Deruxtecan (HER3-DXd; MK-1022) in Non– ... To evaluate the efficacy of patritumab deruxtecan (HER3-DXd) in patients with advanced non–small cell lung cancer without common EGFR-activating ...

3. merck.com merck.com/news/patritumab-deruxtecan-demonstrated-statistically-significant-improvement-in-progression-free-survival-versus-doublet-chemotherapy-in-patients-with-locally-advanced-or-metastatic-egfr-mutated-non-small/

Patritumab Deruxtecan Demonstrated Statistically ... Daiichi Sankyo and Merck's patritumab deruxtecan demonstrates a statistically significant progression-free survival improvement in this EGFR-mutated non-small ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04676477

NCT04676477 | HER3-DXd (Patritumab Deruxtecan; U3- ... This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT381023

Phase 1 study of patritumab deruxtecan (HER3-DXd; U3- ... Efficacy and safety of patritumab deruxtecan (HER3-DXd) in advanced/metastatic non-small cell lung cancer (NSCLC) without EGFR-activating mutations. First ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.9017

Efficacy and safety of patritumab deruxtecan (HER3-DXd) ... These data show promising clinical activity in pts with NSCLC without EGFRm, including pts with other identified driver genomic alterations.

7. asco.org asco.org/abstracts-presentations/ABSTRACT328857

Efficacy and safety of patritumab deruxtecan (HER3-DXd ... Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC). download.