Patritumab Deruxtecan for Non-Small Cell Lung Cancer

Not currently recruiting at 203 trial locations

Overseen By Contact for Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Daiichi Sankyo

Must be taking: EGFR TKIs

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Small cell disease, ILD, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, patritumab deruxtecan, for individuals with non-small cell lung cancer (NSCLC) that has an EGFR mutation. The goal is to determine if this treatment is more effective and gentler on the body than standard chemotherapy options. Participants will either receive the new treatment or continue with standard platinum-based chemotherapy. Suitable candidates have NSCLC with an EGFR mutation and have not had success with other specific treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking advancements in cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on chronic systemic corticosteroids or certain anticoagulants, there may be specific requirements. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that patritumab deruxtecan is generally well-tolerated in past studies. For individuals with EGFR-mutated non-small cell lung cancer, this treatment has shown promise. Although some patients experienced side effects, many were manageable. Common side effects included nausea and low blood cell counts. Despite these, the treatment was deemed safe enough for further research.

Regarding safety, researchers have tested patritumab deruxtecan in individuals who have already tried other treatments, gathering extensive information about its effects. This background may offer reassurance about the treatment's safety for those considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about patritumab deruxtecan because it offers a novel approach to treating non-small cell lung cancer by targeting the HER3 protein, which is not addressed by standard chemotherapy options like pemetrexed with cisplatin or carboplatin. Unlike traditional treatments, patritumab deruxtecan combines an antibody with a chemotherapy drug, delivering the chemotherapy directly to cancer cells with potentially greater precision and effectiveness. This targeted mechanism may lead to more effective cancer cell destruction while minimizing damage to healthy cells, providing a promising alternative for patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

Research has shown that patritumab deruxtecan, one of the treatments in this trial, holds promise for treating non-small cell lung cancer with EGFR mutations. One study found that this treatment helped patients live longer without their cancer worsening compared to standard chemotherapy. In this trial, some participants will receive patritumab deruxtecan, while others will be randomized to receive platinum-based chemotherapy, which serves as the active comparator. Patients who had already tried other treatments also showed positive results with patritumab deruxtecan. This treatment targets a specific protein on cancer cells, allowing cancer-fighting drugs to reach the tumor more effectively. These findings suggest that patritumab deruxtecan could be a more effective and tolerable option for people with advanced lung cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Clinical Scientist

Principal Investigator

Daiichi Sankyo

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Are You a Good Fit for This Trial?

Adults with advanced non-squamous non-small cell lung cancer (NSCLC) that has an EGFR mutation and worsened after EGFR TKI therapy. They should not have had other systemic treatments in the metastatic setting, must be able to perform daily activities with minimal assistance (ECOG PS of 0 or 1), and have adequate organ function.

Inclusion Criteria

My non-squamous NSCLC cannot be cured with surgery or radiation.

My cancer worsened 12 months after initial treatment and progressed after third-gen EGFR treatment.

I am willing to undergo a tumor biopsy or provide recent tumor samples.

Exclusion Criteria

My HIV infection is not well controlled.

I have a serious eye condition affecting my cornea.

I haven't had any cancer except for certain skin cancers and treated cervical cancer 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 are randomized to receive either patritumab deruxtecan or platinum-based chemotherapy. Platinum-based chemotherapy is administered for 4 cycles, and patritumab deruxtecan is administered at 5.6 mg/kg every 3 weeks.

12 weeks

Follow-up

Participants are monitored for progression-free survival and overall survival, as well as treatment-emergent adverse events and other secondary outcomes.

49 months

Maintenance

Participants without disease progression after 4 cycles of platinum-based chemotherapy may continue treatment with maintenance pemetrexed.

What Are the Treatments Tested in This Trial?

Interventions

• Patritumab Deruxtecan
• Platinum-based chemotherapy

Trial Overview The trial is testing Patritumab Deruxtecan against standard platinum-based chemotherapy in patients whose NSCLC has progressed despite previous treatment with EGFR TKI drugs. The goal is to find a more effective and tolerable treatment for these patients.

How Is the Trial Designed?

Group I: Patritumab deruxtecan Experimental Treatment 1 Intervention

Participants who will be randomized to receive patritumab deruxtecan (HER3-DXd) 5.6 mg/kg q3W.

Group II: Platinum-based chemotherapy Active Control 1 Intervention

Participants who will be randomized to receive platinum-based chemotherapy for 4 cycles: pemetrexed plus either cisplatin or carboplatin. Participants without disease progression after 4 cycles of platinum plus pemetrexed therapy may continue treatment with maintenance pemetrexed with no restriction on the number of cycles.

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

Published Research Related to This Trial

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 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]

Irinotecan shows promising efficacy as a treatment for advanced non-small cell lung cancer (NSCLC), with response rates between 13-32% as a single agent and up to 75% when combined with cisplatin, outperforming older treatments.

In small cell lung cancer (SCLC), irinotecan also demonstrates significant activity, achieving response rates of 16-47% alone and up to 79% in combination with cisplatin or etoposide, although it is associated with dose-limiting toxicities like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in cancers of the lung and cervix. Sandler, A., van Oosterom, AT.[2019]

In a phase II study involving 39 patients with completely resected stage II or III non-small cell lung cancer, 92.3% completed four cycles of adjuvant chemotherapy with nedaplatin and irinotecan, indicating high tolerability of this regimen.

The treatment resulted in a median disease-free survival of 49.4 months and a 5-year overall survival rate of 69.8%, suggesting that nedaplatin and irinotecan are effective options for improving outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. Murakami, S., Saito, H., Kondo, T., et al.[2019]

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 study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

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. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00465-6/fulltext

Patritumab deruxtecan (HER3-DXd) in patients with active ... Patritumab deruxtecan (HER3-DXd) in patients with active brain metastases of non-small-cell lung cancer (TUXEDO-3): a multicentre, single-arm, phase 2 trial.

5. 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 ...

6. merck.com merck.com/news/patritumab-deruxtecan-biologics-license-application-for-patients-with-previously-treated-locally-advanced-or-metastatic-egfr-mutated-non-small-cell-lung-cancer-voluntarily-withdrawn/

Patritumab Deruxtecan Biologics License Application for ... The decision to withdraw the BLA is based on topline overall survival (OS) results from the confirmatory HERTHENA-Lung02 Phase 3 trial.

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.