U3-1402 for Non-Small Cell Lung Cancer

Recruiting at 28 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Daiichi Sankyo

Must be taking: EGFR TKIs

Must not be taking: Anti-HER3, Topoisomerase I inhibitors

Disqualifiers: Small cell histology, ILD, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing HER3-DXd, a new drug for advanced lung cancer patients who haven't responded to other treatments. The drug targets a protein on cancer cells and delivers a toxic substance to destroy them.

Will I have to stop taking my current medications?

If you are currently taking erlotinib, gefitinib, afatinib, or osimertinib, you will need to stop these medications to participate in the trial. The protocol does not specify about other medications, so it's best to discuss with the study team.

What data supports the effectiveness of the drug U3-1402 (Patritumab deruxtecan) for non-small cell lung cancer?

Research shows that Patritumab deruxtecan has shown promising results in treating non-small cell lung cancer that has specific mutations, especially after other treatments have failed. It has demonstrated antitumor activity and a tolerable safety profile in patients with these mutations. ^{1 2 3 4 5}

Is Patritumab Deruxtecan (U3-1402) safe for humans?

Patritumab Deruxtecan (also known as HER3-DXd or U3-1402) has been studied in patients with different types of cancer, including lung and breast cancer. In these studies, it showed a tolerable safety profile, meaning that while there were some side effects, they were generally manageable for patients. ^{1 2 3 4 6}

What makes the drug U3-1402 unique for treating non-small cell lung cancer?

U3-1402, also known as Patritumab deruxtecan, is unique because it targets the HER3 protein, which is often found in high levels in certain lung cancers. It combines an antibody that specifically binds to HER3 with a cancer-killing drug, making it a novel option for patients whose cancer has progressed after other treatments. ^{1 2 3 7 8}

Research Team

Global Clinical Lead

Principal Investigator

Daiichi Sankyo

Eligibility Criteria

This trial is for adults with advanced or inoperable non-small cell lung cancer (NSCLC) who have previously been treated with EGFR tyrosine kinase inhibitors. Participants must have at least one measurable lesion, be in good physical condition (ECOG status of 0 or 1), and not have other active cancers or serious heart conditions.

Inclusion Criteria

My cancer has a specific EGFR mutation.

You have at least one specific area of your body that can be measured to see if the treatment is working.

I am currently taking a specific cancer medication but can stop if needed.

Exclusion Criteria

You have any important irregularities in your resting electrocardiogram (ECG).

My cancer biopsy shows small cell or mixed small cell and non-small cell features.

I cannot or will not stop taking medications that may affect my heart's rhythm.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

HER3-DXd is evaluated in participants with metastatic or unresectable NSCLC with EGFR activating mutation after disease progression during/after EGFR TKI therapy to assess safety and tolerability and determine the recommended dose for expansion

Approximately 36 months

Every 3 weeks

Dose Expansion

HER3-DXd is evaluated in participants with metastatic or unresectable NSCLC with EGFR activating mutation or squamous or non-squamous NSCLC with disease progression during/after systemic treatment for locally advanced or metastatic disease to investigate antitumor activity

Approximately 36 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 24 months

Treatment Details

Interventions

• U3-1402 (Antibody-Drug Conjugate)

Trial Overview The study tests U3-1402, a new drug for NSCLC. It has two parts: Dose Escalation to find the safe dosage for those with an EGFR mutation after TKI therapy failure, and Dose Expansion to assess effectiveness in broader NSCLC cases post systemic treatment failure.

Participant Groups

Group I: Dose Expansion: Cohort 5, KRAS-G12C mutant NSCLC Experimental Treatment 1 Intervention

Participants with locally advanced or metastatic NSCLC whose tumors harbor a KRAS-G12C mutation and that have progressed on the most recent line of therapy will receive HER3-DXd IV at 5.6 mg/kg every 3 weeks.

Group II: Dose Expansion: Cohort 4, EGFR mutant Experimental Treatment 1 Intervention

Participants with NSCLC (including any histology other than small-cell or combined small-cell and non-small cell) with an EGFR-activating mutation will receive HER3-DXd IV at 5.6 mg/kg every 3 weeks.

Group III: Dose Expansion: Cohort 3b, EGFR mutant Experimental Treatment 1 Intervention

Randomized participants with NSCLC and EGFR mutations in the Dose Expansion Cohort 3b will receive HER3-DXd IV once every three weeks following an up-titration regimen (Cycle 1, Day 1: 57% of RDE or aRDE; Cycle 2, Day 1: 86% of RDE or, if applicable aRDE; Cycle 3 and subsequent cycles, Day 1: 114% of RDE or aRDE).

Group IV: Dose Expansion: Cohort 3a, EGFR mutant Experimental Treatment 1 Intervention

Randomized participants with NSCLC and EGFR mutations in the Dose Expansion Cohort 3a will receive HER3-DXd IV once every three weeks at the established recommended dose for expansion (RDE) or, if applicable, adjusted RDE (aRDE).

Group V: Dose Expansion: Cohort 2, EGFR wild-type Experimental Treatment 1 Intervention

Participants with squamous or non-squamous NSCLC without EGFR-activating mutations in the Dose Expansion Cohort 2 will receive HER3-DXd IV once every three weeks at the established recommended dose for expansion (RDE).

Group VI: Dose Expansion: Cohort 1, EGFR mutant Experimental Treatment 1 Intervention

Participants with adenocarcinoma NSCLC with EGFR mutations in the Dose Expansion Cohort 1 will receive HER3-DXd IV once every three weeks at the established recommended dose for expansion (RDE).

Group VII: Dose Escalation: Cohort 4, 6.4 mg/kg Experimental Treatment 1 Intervention

Participants in Dose Escalation Cohort 3 will receive HER3-DXd intravenously (IV) once every three weeks at 6.4 mg/kg.

Group VIII: Dose Escalation: Cohort 3, 5.6 mg/kg Experimental Treatment 1 Intervention

Participants in Dose Escalation Cohort 3 will receive HER3-DXd intravenously (IV) once every three weeks at 5.6 mg/kg.

Group IX: Dose Escalation: Cohort 2, 4.8 mg/kg Experimental Treatment 1 Intervention

Participants in Dose Escalation Cohort 2 will receive HER3-DXd intravenously (IV) once every three weeks at 4.8 mg/kg.

Group X: Dose Escalation: Cohort 1, 3.2 mg/kg Experimental Treatment 1 Intervention

Participants in the Dose Escalation Cohort 1 will receive HER3-DXd intravenously (IV) once every three weeks at 3.2 mg/kg.

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 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) 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 (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]

The study is investigating the HER3-directed antibody drug conjugate patritumab deruxtecan (HER3-DXd) in patients with HR-positive/HER2-negative early breast cancer, focusing on its biological effects after a single dose.

The primary endpoint is to assess the CelTIL score, which will help evaluate the drug's impact on the tumor microenvironment and resistance mechanisms, providing valuable insights into its efficacy and potential as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer. Pascual, T., Oliveira, M., Ciruelos, E., et al.[2021]

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 of 77 patients with early breast cancer, a single dose of patritumab deruxtecan (HER3-DXd) significantly increased the CelTIL score, indicating enhanced immune infiltration and a shift towards a less proliferative tumor phenotype.

The treatment showed a clinical response rate of 45% among patients, with most experiencing manageable side effects, suggesting HER3-DXd has a tolerable safety profile and warrants further investigation in early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. Oliveira, M., Falato, C., Cejalvo, JM., 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]

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 (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]

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. Switzerland pubmed.ncbi.nlm.nih.gov

SOLTI-1805 TOT-HER3 Study Concept: A Window-of-Opportunity Trial of Patritumab Deruxtecan, a HER3 Directed Antibody Drug Conjugate, in Patients With Early Breast Cancer. [2021]

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

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

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

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

7. England pubmed.ncbi.nlm.nih.gov

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study. [2023]

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

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