Patritumab Deruxtecan for Non-Small Cell Lung Cancer

Recruiting at 178 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

586 Participants Needed

Trial Summary

What is the purpose of this trial?

Disease progression is typical for patients with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). Standard platinum-based chemotherapy offers limited efficacy and an unfavorable safety profile.There is an urgent need for more effective and tolerable therapies for patients with EGFRm NSCLC who have exhausted available targeted therapies. Clinical evidence suggest that patritumab deruxtecan constitutes a promising investigational therapy for patients with EGFRm NSCLC.

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.

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

Irinotecan, a component of the treatment, has shown effectiveness in treating advanced non-small cell lung cancer (NSCLC) with response rates of 13-32% as a single agent and 29-75% when combined with cisplatin, which is part of the chemotherapy regimen in the trial. ^{1 2 3 4 5}

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

Patritumab Deruxtecan is unique because it targets HER3, a protein highly expressed in certain lung cancers, using an antibody-drug conjugate that combines a HER3 antibody with a cancer-killing agent, offering a new option for patients whose cancer has progressed after other treatments. ^{6 7 8 9 10}

Research Team

Global Clinical Leader

Principal Investigator

Daiichi Sankyo

Clinical Scientist

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

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

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.

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 (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]

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

Phase II trial of cetuximab plus cisplatin and irinotecan in patients with cisplatin and irinotecan-refractory metastatic esophagogastric cancer. [2018]

2. England 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. [2018]

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

Irinotecan in cancers of the lung and cervix. [2019]

4. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of nedaplatin and irinotecan as adjuvant chemotherapy for completely resected non-small cell lung cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Phase I study of carboplatin, docetaxel and irinotecan with recombinant human granulocyte colony stimulating factor support in patients with advanced non-small cell lung cancer. [2019]

6. 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]

7. 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]

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

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

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

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

10. England pubmed.ncbi.nlm.nih.gov

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