HERTHENA-Lung01: A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

Plain English Summary

HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer is a Phase 2 clinical trial sponsored by Daiichi Sankyo studying Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor. This trial tests a new drug called patritumab deruxtecan for advanced lung cancer. It is for patients with non-small cell lung cancer (NSCLC) that has spread or cannot be removed by surgery, and has a specific genetic change (EGFR mutation). Participants will receive the study drug intravenously and will have regular check-ups. Standard treatments for this type of lung cancer include other targeted therapies and chemotherapy. The trial aims to enroll 277 participants.

Official Summary

This study is designed to evaluate the antitumor activity of patritumab deruxtecan in participants with metastatic or locally advanced NSCLC with an activating EGFR mutation (exon 19 deletion or L858R) who have received and progressed on or after at least 1 EGFR TKI and 1 platinum-based chemotherapy-containing regimen.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with advanced or metastatic non-small cell lung cancer. Patients must have a specific EGFR gene mutation (exon 19 deletion or L858R). Must have previously been treated with at least one EGFR targeted therapy (like osimertinib) and one platinum-based chemotherapy. Patients must have measurable disease and be well enough to participate (ECOG performance status of 0 or 1). This trial is studying Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see how often the study drug shrinks tumors, which indicates it is working to control the cancer. The specific primary outcome measures are: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for new treatments for patients with EGFR-mutated lung cancer who have stopped responding to existing therapies. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-Small Cell Lung Cancer Metastatic, Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor, where improved treatment options are needed.

Investor Insight

This trial is investigating a novel antibody-drug conjugate, a promising class of therapies, for a well-defined patient population, suggesting potential for significant clinical impact and market pene Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your lung cancer has an EGFR mutation and if you have progressed on prior treatments. Understand that you will receive the study drug through an IV infusion, and will need to attend regular appointments for monitoring. Be prepared to provide tumor tissue samples for testing. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 277 participants

Interventions

• DRUG: Patritumab Deruxtecan (Fixed dose) — Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
• DRUG: Patritumab Deruxtecan (Up-Titration) — Patritumab deruxtecan will be dosed as an intravenous (IV) infusion administered at Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and subsequent cycles, 6.4 mg/kg administered on Day 1 of each 21-day cycle.

Primary Outcomes

• Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)

Secondary Outcomes

• Duration of Response (DoR) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)
• Progression-free Survival (PFS) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)
• Objective Response Rate (ORR) as Assessed by the Investigator (Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)
• Disease Control Rate (DCR) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)
• Time to Tumor Response (TTR) (Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months)

Full Eligibility Criteria

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for inclusion in this study.

* Sign and date the tissue informed consent form (ICF) and the main ICF, prior to the start of any study-specific qualification procedures.
* Male or female participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old).
* Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.
* Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Participants must have received both of the following:

  * Prior treatment with osimertinib. Participants receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. Participants in South Korea known to harbor a clinically actionable genomic alteration in addition to EGFR mutation (e.g., anaplastic lymphoma kinase \[ALK\] or ROS1 protocol oncogene 1 \[ROS1\] fusion) for which treatment is available must have also received prior treatment with at least 1 approved genotype-directed therapy, unless unable (i.e., if contraindicated). No new testing for these genomic alterations (e.g., ALK or ROS1 fusion) is required for Screening.
  * Systemic therapy with at least 1 platinum-based chemotherapy regimen.
* Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R.
* At least 1 measurable lesion confirmed by BICR as per RECIST v1.1
* Consented and willing to provide required tumor tissue of sufficient quantity and of adequate tumor tissue content. Required tumor tissue can be provided as either:

  * Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
  * Archival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen.
* Eastern Cooperative Oncology Group Performance Standard of 0 or 1 at Screening.
* Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1:

  * Platelet count : ≥100,000/mm\^3 or ≥100 × 10\^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)
  * Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
  * Absolute neutrophil count: ≥1500/mm\^3 or ≥1.5 × 10\^9/L
  * Serum creatinine (SCr) or creatinine clearance (CrCl): SCr ≤1.5 × upper limit of normal (ULN), OR CrCl ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl
  * Aspartate aminotransferase/alanine aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
  * Total bilirubin: ≤1.5 × ULN if no liver metastases (\<3 × ULN in the presence of documented Gilbert's syndrome \[unconjugated hyperbilirubinemia\] or liver metastases)
  * Serum albumin: ≥2.5 g/dL
  * Prothrombin time (PT) or PT-International normalized ratio (INR) and activated partial thromboplastin time (aPTT)/PTT: ≤1.5 × ULN, except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study.

* Any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.
* Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
* Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

  * Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\]), restrictive lung disease, pleural effusion);
  * Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.
* Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
* Evidence of any leptomeningeal disease.
* Evidence of clinically active spinal cord compression or brain metastases.
* Inadequate washout period prior to Cycle 1

Trial Locations

• Banner MD Anderson Cancer Center, Gilbert, Arizona, United States
• City of Hope, Duarte, California, United States
• Moores Cancer Center at the UC San Diego Health, La Jolla, California, United States
• Pacific Shores Medical Group, Long Beach, California, United States
• USC Norris Comprehensive Cancer Center, Los Angeles, California, United States
• University of California at Irvine, Orange, California, United States
• Cedars Sinai, West Hollywood, California, United States
• University of Colorado Denver - Anschutz Medical Campus, Aurora, Colorado, United States
• Florida Cancer Specialists - South, Fort Myers, Florida, United States
• AdventHealth Orlando, Orlando, Florida, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Non-Small Cell Lung Cancer
• Metastatic Lung Cancer
• EGFR-mutated Lung Cancer
• Lung Adenocarcinoma
• Targeted Cancer Therapy
• Chemotherapy Resistance
• Oncology
• Pulmonary Oncology
• Genomic Medicine
• Precision Medicine

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