Clinical Trials /

HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer

NCT04619004

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: U31402-A-U201
  • SECONDARY ID: 2020-000730-17
  • NCT ID: NCT04619004

Conditions

  • Non-Small Cell Lung Cancer Metastatic
  • Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor

Interventions

DrugSynonymsArms
Patritumab Deruxtecan (Fixed dose)U3-1402, HER3-DXdStudy Group 1: Patritumab deruxtecan 5.6 mg/kg
Patritumab Deruxtecan (Up-Titration)U3-1402, HER3-DXdStudy Group 2: Patritumab deruxtecan Up-Titration

Purpose

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.

Detailed Description

      This study will initially randomize participants to one of 2 arms in a 1:1 ratio to receive
      either a 5.6 mg/kg fixed dose regimen or an up-titration dose regimen of patritumab
      deruxtecan (HER3-DXd, U3-1402).
    

Trial Arms

NameTypeDescriptionInterventions
Study Group 1: Patritumab deruxtecan 5.6 mg/kgExperimentalStudy 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 Q3W
  • Patritumab Deruxtecan (Fixed dose)
Study Group 2: Patritumab deruxtecan Up-TitrationExperimentalStudy Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV Q3W
  • Patritumab Deruxtecan (Up-Titration)

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:

               -  ≥ 1 prior line(s) of EGFR TKI treatment (erlotinib, gefitinib, afatinib,
                  dacomitinib or osimertinib). Participants receiving an EGFR TKI at the time of
                  signing informed should continue to take the EGFR TKI until 5 days prior to Cycle
                  1 Day 1. EGFR T790M mutation-positive participants (previously treated with
                  erlotinib, gefitinib, afatinib or dacomitinib) must have received and have
                  documentation of radiological disease progression following treatment with
                  osimertinib.

               -  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.

          -  ECOG PS 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 of 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 Day 1, defined as:

               -  Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7
                  days;

               -  Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s)
                  from a previous cancer treatment regimen or clinical study (other than EGFR TKI),
                  <14 days or 5 half-lives, whichever is longer;

               -  Monoclonal antibodies, other than immune checkpoint inhibitors, such as
                  bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) <28 days;

               -  Immune checkpoint inhibitor therapy <21 days;

               -  Major surgery (excluding placement of vascular access) <28 days;

               -  Radiotherapy treatment to more than 30% of the bone marrow or with a wide field
                  of radiation <28 days or palliative radiation therapy <14 days; or

               -  Chloroquine or hydroxychloroquine <14 days.

          -  Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody
             or single-agent topoisomerase I inhibitor.

          -  Prior treatment with an antibody drug conjugate (ADC) that consists of any
             topoisomerase I inhibitor

          -  Has unresolved toxicities from previous anticancer therapy, defined as toxicities
             (other than alopecia) not yet resolved to National Cancer Institute Common Terminology
             Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade ≤1 or baseline. Participants with
             chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after
             consultation with the Sponsor Medical Monitor or designee.

          -  Has history of other active malignancy within 3 years prior to enrollment, except:

               -  Adequately treated non-melanoma skin cancer;

               -  Superficial bladder tumors (Ta, Tis, T1);

               -  Adequately treated intraepithelial carcinoma of the cervix uteri;

               -  Low risk non-metastatic prostate cancer (with Gleason score <7, and following
                  local treatment or ongoing active surveillance);

               -  Any other curatively treated in situ disease.

          -  Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1

          -  Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence
             of viral infection within 28 days of Cycle 1 Day 1.

          -  Participant with any human immunodeficiency virus (HIV) infection.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
Time Frame: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 26 months
Safety Issue:
Description:ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame: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 26 months
Safety Issue:
Description:DoR is defined as the time from the first documented confirmed response (CR or PR) to the date of progression or death due to any cause as assessed by BICR and Investigator per RECIST v1.1, respectively.
Measure:Progression-free Survival (PFS)
Time Frame: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 26 months
Safety Issue:
Description:PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of objective progressive disease (PD) per RECIST v1.1 or death due to any cause. PFS will be determined by BICR and by Investigator, respectively.
Measure:Objective Response Rate (ORR) as Assessed by the Investigator
Time Frame:Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 26 months
Safety Issue:
Description:ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR as assessed by the Investigator per RECIST v1.1.
Measure:Disease Control Rate (DCR)
Time Frame: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 26 months
Safety Issue:
Description:DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) as assessed by BICR and by the Investigator per RECIST v1.1, respectively.
Measure:Time to Tumor Response (TTR)
Time Frame: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 26 months
Safety Issue:
Description:TTR is defined as the time from the start of study treatment to the date of the first documentation of confirmed response (CR or PR) as assessed by BICR and Investigator per RECIST v1.1, respectively.
Measure:Best percentage change in the sum of diameters (SoD) of measurable tumors
Time Frame: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 26 months
Safety Issue:
Description:The best percentage change in the SoD of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.
Measure:Overall Survival (OS)
Time Frame:Death date is collected until the participant discontinues the study or up to approximately 26 months
Safety Issue:
Description:OS defined as the time from the start of study treatment to the date of death due to any cause.
Measure:Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)
Time Frame:From baseline up to Day 47 post last dose
Safety Issue:
Description:A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. Adverse events will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Non-Small Cell Lung Cancer Metastatic
  • Non-Small Cell Lung Cancer with Mutation in Epidermal Growth Factor Receptor
  • Epidermal growth factor receptor
  • HER3-DXd
  • Patritumab Deruxtecan
  • U3-1402

Last Updated

January 22, 2021