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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04619004

Studienbeginn:
Februar 2021

Letztes Update:
09.03.2021

Wirkstoff:
Patritumab Deruxtecan (Fixed dose), Patritumab Deruxtecan (Up-Titration)

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Daiichi Sankyo, Inc.

Collaborator:
Daiichi Sankyo Co., Ltd.

Studienleiter

Medical Director
Study Director
Daiichi Sankyo, Inc.

Kontakt

(US sites only) Daiichi Sankyo Contact for Clinical Trial Information
Kontakt:
Phone: 908-992-6400
E-Mail: CTRinfo@dsi.com» Kontaktdaten anzeigen
(Asia sites only) Daiichi Sankyo Contact for Clinical Trial Information
Kontakt:
Phone: +81-3-6225-1111(M-F 9-5 JST)
E-Mail: dsclinicaltrial@daiichisankyo.co.jp» Kontaktdaten anzeigen

Studienlocations
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Studien-Informationen

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).

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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):
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:

1. 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):
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.

2. 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):
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.

3. 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):
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.

4. 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):
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.

5. 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):
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.

6. 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):
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.

7. Overall Survival (OS) (Time Frame - Death date is collected until the participant discontinues the study or up to approximately 26 months):
OS defined as the time from the start of study treatment to the date of death due to any cause.

8. 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):
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.

Studien-Arme

  • Experimental: Study Group 1: Patritumab deruxtecan 5.6 mg/kg
    Study 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
  • Experimental: Study Group 2: Patritumab deruxtecan Up-Titration
    Study 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

Geprüfte Regime

  • Patritumab Deruxtecan (Fixed dose) (U3-1402 / HER3-DXd / ):
    Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
  • Patritumab Deruxtecan (Up-Titration) (U3-1402 / HER3-DXd / ):
    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.

Quelle: ClinicalTrials.gov


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