AzTrials
AzTrials

Non-Small Cell Lung Cancer (NSCLC)Phase 1NCT04676477

HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer

A Phase 1 study testing HER3-DXd and Osimertinib in people with Non-Small Cell Lung Cancer (NSCLC), run by Daiichi Sankyo at 31 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety. The primary objectives: Dose Escalation: To assess the safety and tolerability of HER3-DXd (patritumab deruxtecan; U3-1402) and osimertinib in subjects with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer (NSCLC)
What is being tested?
HER3-DXd and Osimertinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
246 participants
Where
31 sitesin 4 countries
Study dates
11 Jun 2021to 14 Dec 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Inclusion Criteria Specific to Dose Escalation and Second-line Dose Expansion:
  • Documentation of EGFR exon 19 deletion or L858R mutation detected from tumor tissue
  • Must have received osimertinib for locally advanced or metastatic disease at a dose of 80 mg once daily (QD) for at least 6 weeks and must not miss more than two doses during the 2 weeks prior to the first day of study treatment (Cycle 1, Day 1)
  • Must not have received any other prior systemic cancer therapies in the locally advanced/metastatic setting
  • Has documentation of radiological disease progression following first-line treatment with osimertinib in the locally advanced or metastatic setting
  • The tumor tissue harbors one of the 2 common EGFR mutations occurring in NSCLC known to be associated with EGFR-TKI sensitivity (exon 19 deletion or L858R) as assessed by Clinical Laboratory Improvement Amendments (CLIA)-certified (United States [US] sites), accredited (outside of the US), local laboratory or central laboratory. Only tissue-based testing will be accepted.
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  • Participants must have previously untreated locally advanced or metastatic NSCLC and must be eligible to receive first-line treatment with osimertinib, according to the judgment of the investigator. Prior adjuvant or neo-adjuvant therapy (chemotherapy, radiotherapy, investigational agents; except with osimertinib) is permitted.
  • All Participants:
  • Participants must meet all criteria to be eligible for inclusion in this study:
  • Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.
  • At least 1 measurable lesion as assessed by Investigator as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
  • Tissue requirements
  • For Dose Escalation (all cohorts): provide an optional pre-treatment tumor tissue of sufficient quantity, as defined in the laboratory manual. The optional pre-treatment tumor tissue can be provided as either:
  • Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
  • Archival tissue collected from a biopsy performed prior to signing of the tissue consent, and since progression while on treatment with the most recent cancer therapy
  • For First-line Dose Expansion (Cohorts 3, 4a, and 4b): provide an optional pre-treatment and optional on-treatment tumor tissues of sufficient quantity, as defined in the laboratory manual. The optional pre-treatment tumor tissue can be provided as either:
  • Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
  • Archival tissue collected from a biopsy performed at the time of initial diagnosis or later
  • For Second-line Dose Expansion (Arm 1, Arm 2, and Arm 1b): provide a required pre-treatment and required on-treatment tumor tissues of sufficient quantity, as defined in the laboratory manual. The required pre-treatment tumor tissue can be provided as either:
  • Pre-treatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
  • Archival tissue collected from a biopsy performed prior to signing of the tissue consent, and since progression while on treatment with the most recent cancer therapy regimen
  • Note: For all participants who consent to a pre-treatment biopsy, in order to ensure an adequate amount of tissue is available, a core needle biopsy is required.
  • Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1, Day 1 (Dose Escalation and First-line Dose Expansion) or within 14 days prior to randomization (Second-line Dose Expansion):
  • Platelet count: ≥100 000/mm^3 or ≥100 × 10^9/L (platelet transfusions are not allowed within 14 days prior to the assessment of platelets during the screening period in order to meet the study inclusion criterion)
  • Hemoglobin: ≥9.0 g/dL (transfusion of red blood cells and/or growth factor support is not allowed within 14 days prior to the assessment of hemoglobin during the screening period in order to meet the study inclusion criterion)
  • Absolute neutrophil count (ANC): 1500/mm^3 or ≥1.5 × 10^9/L (granulocyte colony stimulating factor support is not allowed within 14 days prior to the assessment of ANC during the screening period in order to meet the study inclusion criterion)
  • Creatinine clearance (CrCl): 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
  • Alkaline phosphatase (ALP) and Gamma-glutamyl transferase (GGT): ≤2.5 × ULN of both ALP and GGT
  • Prothrombin time (PT) or PT-international normalized ratio (INR) and Activated partial thromboplastin time (aPTT) / Partial thromboplastin time (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.

Who cannot join

  • Any previously documented histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease
  • Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroid therapy, has current ILD, or is suspected to have such disease by imaging during screening.
  • Clinically severe pulmonary compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:
  • Any underlying pulmonary disorder (eg, pulmonary emboli within three months of the study enrollment or randomization, severe asthma, severe chronic obstructive pulmonary disease, 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 activity or any form of immunosuppressive therapy prior to Cycle 1, Day 1. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
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  • Evidence of any leptomeningeal disease.
  • Has spinal cord compression or clinically active central nervous system metastases, defined as symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study, but must have a stable neurologic status for at least 4 weeks prior to Cycle 1, Day 1. Participants with asymptomatic brain metastases and treated with anticonvulsants as prophylaxis are able to enroll following a 14-day washout period. Note: A CT or MRI scan of the brain at baseline is required for all participants.
  • Inadequate washout period prior to Cycle 1, Day 1 defined as:
  • Whole brain radiation therapy <28 days or stereotactic brain radiation therapy <7 days;
  • Any systemic anticancer therapy (excluding osimertinib in all Dose Escalation Cohorts and in Second-line Dose Expansion [Arm 1, Arm 2, and Arm 1b]), including investigational agents, <14 days or 5 half-lives, whichever is longer
  • Immune checkpoint inhibitor therapy ≤21 days
  • Major surgery (excluding placement of vascular access) <4 weeks
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation < 28 days or palliative radiation therapy <7 days
  • Chloroquine or hydroxychloroquine ≤14 days
  • Medications or herbal supplemented known to be strong inducers of cytochrome P450 (CYP) 3A4 <21 days.
  • 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) version 5.0, Grade ≤1 or baseline. Subjects with chronic Grade 2 toxicities may be eligible per the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow osimertinib, or previous significant bowel resection that would preclude adequate absorption of osimertinib.
  • Has any primary malignancy other than locally advanced or metastatic NSCLC within 3 years prior to Cycle 1, Day 1 (Dose Escalation and First-line Dose Expansion) or within 3 years prior to randomization (Second-Line Dose Expansion), except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated.
  • Uncontrolled or significant cardiovascular disease prior to Cycle 1, Day 1 including:
  • Mean corrected QT interval using Fridericia's formula (QTcF) interval of >450 ms in 3 successive central screening measurements
  • Left ventricular ejection fraction (LVEF) ≤50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan
  • Resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg
  • Myocardial infarction within 6 months
  • New York Heart Association (NYHA) Classes 2 to 4 congestive heart failure within 28 days
  • Uncontrolled angina pectoris within 6 months
  • Has cardiac arrhythmia requiring antiarrhythmic treatment
  • Complete left or right bundle branch block within 6 months
  • History of second- or third-degree heart block or PR interval >250 ms within 6 months
  • History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
  • Has any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval
  • Has clinically significant corneal disease
  • Any evidence of severe or uncontrolled diseases including active bleeding diatheses, active infection, psychiatric illness/social situations, geographical factors, substance abuse, or other factors which in the Investigator's opinion makes it undesirable for the subject to participate in the study or which would jeopardize compliance with the protocol. Screening for chronic conditions is not required.
  • Has a known human immunodeficiency virus (HIV) infection that is not well controlled.

Trial locations and contacts

31 sites in 4 countries.

31 sites in 4 countries

United States13 sites
  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

  • Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Sarah Cannon and HCA Research Institute

    Nashville, Tennessee, 37203

  • Yale University School of Medicine - Yale-New Haven Hospital

    New Haven, Connecticut, 06510

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • UCLA

    Santa Monica, California, 90404

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20057

Other trials in United States

Japan10 sites
  • National Cancer Center Hospital

    Chuo Ku, Tokyo, 104-0045

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, Fukuoka, 811-1395

  • National Hospital Organization Iwakuni Clinical Center

    Iwakuni-shi, Yamaguchi, 740-8510

  • National Hospital Organization Shikoku Cancer Center

    Matsuyama, Ehime, 791-0280

  • Okayama University Hospital

    Okayama, Okayama-ken, 700-8558

  • Kindai University Hospital

    Ōsaka-sayama, 589-8511

  • National Hospital Organization Hokkaido Cancer Center

    Sapporo, Hokkaido, 003-0804

  • Shizuoka Cancer Center

    Shizuoka, 411-8777

  • The Cancer Institute Hospital of JFCR

    Tokyo, 135-8550

  • Kanagawa Cancer Center

    Yokohama, Kanagawa, 241-8515

Other trials in Japan

South Korea4 sites
  • Seoul National University Hospital

    Seoul, 03080

  • Yonsei University Health System - Severance Hospital

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Taiwan4 sites
  • Chung Shan Medical University Hospital

    Taichung, 40201

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Medical University Hospital

    Taipei, 110301

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

About this study

Official title: A Phase 1 Open-Label Study of HER3-DXd (Patritumab Deruxtecan; U3-1402) in Combination With Osimertinib in Subjects With Locally Advanced or Metastatic EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

This study includes a Dose Escalation Part to identify the recommended combination dose (RCD) and a Dose Expansion Part to further evaluate efficacy and safety.

The primary objectives:

Read more

Dose Escalation: To assess the safety and tolerability of HER3-DXd (patritumab deruxtecan; U3-1402) and osimertinib in subjects with locally advanced or metastatic non-small cell lung cancer (NSCLC) with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib, and to determine the recommended combination dose (RCD).

Second-Line Dose Expansion Arm 1 and Arm 1b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. Note: One or both of the study arms may open with one or two distinct dosing schedules.

Second-Line Dose Expansion Arm 2: To assess the preliminary antitumor activity of HER3-DXd monotherapy in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib.

First-Line Dose Expansion Cohorts 3, 4a, and 4b: To assess the preliminary antitumor activity of HER3-DXd and osimertinib in subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation without prior systemic treatment for locally advanced or metastatic disease.

Read the detailed description

Dose Escalation:

Population includes subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib. The starting combination dose regimen is HER3-DXd 3.2 mg/kg IV every 21 days (Q3W) and osimertinib 80 mg orally (PO) once daily. At least 3 to 6 subjects will be enrolled in each cohort.

Dose Expansion: Two subject populations will be evaluated in the Dose Expansion Part:

  • Second-Line: Subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation with tumor progression after treatment with osimertinib
  • First-Line: Subjects with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or L858R mutation, and without prior systemic therapy for advanced or metastatic disease. Note: The first line expansion will only be initiated if the RCD includes osimertinib 80 mg PO once daily.
Being tested
HER3-DXd, Osimertinib
Keywords
Advanced Non-small Cell Lung Cancer, Inoperable Non-small Cell Lung Cancer, HER3-DXd (Patritumab Deruxtecan; U3-1402), Unresectable, Epidermal growth factor receptor, Metastatic, EGFR, Osimertinib, HER3
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HER3-DXdDrug

    Also called U3-1402, Patritumab deruxtecan

    Intravenous infusion at a starting dose of 3.2 mg/kg Q3W

  • HER3-DXdDrug

    Also called U3-1402, Patritumab deruxtecan

    Intravenous infusion at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)

  • OsimertinibDrug

    Oral administration at 40 mg or 80 mg once daily

  • OsimertinibDrug

    Oral administration at RCD 1 (and at RCD 2 if two provisional RCDs are selected in dose escalation)

  • HER3-DXdDrug

    Also called U3-1402, Patritumab deruxtecan

    Intravenous infusion 5.6 mg/kg Q3W

  • HER3-DXdDrug

    Also called U3-1402, Patritumab deruxtecan

    Intravenous infusion 4.8 mg/kg Q3W

  • OsimertinibDrug

    Oral administration at 80 mg once daily

Study groups in NCT04676477
Study groupRoleWhat they receive
Dose Escalation: HER3-DXd + osimertinibExperimentalParticipants in the Dose Escalation phase will receive HER3-DXd IV Q3W + osimertinib PO once daily. The dose of HER3-DXd in the first cohort will be 3.2 mg/kg Q3W. The dose of osimertinib in the first cohort will be 80 mg PO once daily.
Receives: Drug: HER3-DXd; Drug: Osimertinib
Second-line Dose Expansion: HER3-DXd + osimertinib (RCD)ExperimentalParticipants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd + osimertinib at the RCD
Receives: Drug: HER3-DXd; Drug: Osimertinib
Second-line Dose Expansion: HER3-DXdExperimentalParticipants in the Second-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W
Receives: Drug: HER3-DXd
First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 3; RCD)ExperimentalIf the RCD includes an osimertinib dose of 80 mg PO once daily, then participants will receive treatment with HER3-DXd and osimertinib at the RCD
Receives: Drug: HER3-DXd; Drug: Osimertinib
First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4a)ExperimentalParticipants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 5.6 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.
Receives: Drug: HER3-DXd; Drug: Osimertinib
First-line Dose Expansion: HER3-DXd + osimertinib (Cohort 4b)ExperimentalParticipants in the First-line Dose Expansion phase will be randomized to receive HER3-DXd 4.8 mg/kg IV Q3W and osimertinib dose of 80 mg PO once daily.
Receives: Drug: HER3-DXd; Drug: Osimertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation: Incidence of Dose-limiting Toxicities (DLT), Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)

    A DLT is defined as any TEAE not attributable to disease or disease-related processes that occurs during the DLT evaluation period and is ≥Grade 3, as defined in the protocol. 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. AEs will be coded using MedDRA and graded using NCI-CTCAE v5.0.

    Measured: From signing of informed consent form up to 40 days (+7 days) after the last dose of study drugs, up to approximately 9 months

  2. Second-line Dose Expansion and First-line Dose Expansion: Objective Response Rate (ORR)

    ORR is defined as the proportion of participants who achieved a best overall response of confirmed complete response (CR) or confirmed partial response (PR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1.

    Measured: From start of study treatment until date of documented disease progression or other protocol-defined reason for discontinuation from the study (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 18 months

Secondary outcomes (13)
  1. Dose Escalation: Objective Response Rate (ORR)

    ORR is defined as the proportion of participants who achieved a best overall response of confirmed CR or confirmed PR as assessed by BICR and Investigator per RECIST v1.1.

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  2. Second-line Dose Expansion and First-line Dose Expansion: Objective Response Rate (ORR)

    ORR is defined as the proportion of participants who achieved a best overall response of confirmed CR or PR as assessed by Investigator per RECIST v1.1.

    Measured: From start of study treatment until the date of documented disease progression or other protocol-defined reason for discontinuation from the study (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 18 months

  3. Dose Escalation, Second-line Dose Expansion, and First-Line Dose Expansion: Duration of Response (DoR)

    DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. DoR as assessed by BICR and Investigator per RECIST v1.1

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  4. Second-line Dose Expansion: Clinical Benefit Rate (CBR)

    CBR is defined as the proportion of participants who have a confirmed best overall response of CR, PR, or SD that lasts for at least 180 days as assessed by BICR and Investigator per RECIST v1.1.

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  5. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Disease Control Rate (DCR)

    DCR is defined as the proportion of participants who achieved a best overall response of confirmed CR, confirmed PR, or stable disease (SD) as assessed by BICR and by Investigator per RECIST v1.1.

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  6. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Time to Response (TTR)

    TTR is defined as the time from the start of study treatment to the date of the first documentation of response (confirmed CR or confirmed PR) in responding participants as assessed by BICR and by Investigator per RECIST v1.1.

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  7. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Progression-free Survival (PFS)

    PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD as assessed by BICR and by Investigator per RECIST v1.1. or death due to any cause, whichever occurs first

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  8. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Overall Survival (OS)

    OS is defined as the time from the start of study treatment to the date of death due to any cause.

    Measured: From start of treatment until date of disease progression or other reason for discontinuation (e.g, withdrawal of consent, lost to follow-up), whichever occurs first, up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  9. Second-line Dose Expansion and First-line Dose Expansion: Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI)

    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.

    Measured: From signing of informed consent form up to 40 (+7 days) days after the last dose of study drugs, up to approximately 18 months

  10. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA

    The immunogenicity of HER3-DXd will be assessed.

    Measured: From the start of study treatment until the end of treatment or study discontinuation (whichever occurs first), up to approximately 9 months (Dose Escalation) and 18 months (Dose Expansion)

  11. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Maximum Concentration (Cmax)

    Cmax will be assessed for HER3-DXd (anti-HER3-ac-DXd, total anti-HER3 antibody LC-MS and DXd), osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2).

    Measured: HER3-DXd: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)

  12. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Time to Maximum Concentration (Tmax)

    Tmax will be assessed for HER3-DXd (anti-HER3-ac-DXd, total anti-HER3 antibody LC-MS and DXd), osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2).

    Measured: HER3-DXd: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)

  13. Dose Escalation, Second-line Dose Expansion, and First-line Dose Expansion: Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC)

    AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for HER3-DXd (anti-HER3-ac-DXd, total anti-HER3 antibody LC-MS and DXd), osimertinib (except for Second-line Dose Expansion Arm 2), and AZ5104 (active metabolite of osimertinib; except for Second-line Dose Expansion Arm 2).

    Measured: HER3-DXd: Cycles 1 and 3, Day 1 pre- and postdose, 4 hours (h), Days 8 and 15; Cycle 2, Day 1 pre- and postdose; Cycles 4, 6, 8, Day 1 pre- and postdose; Osimertinib: Cycles 1, 2, and 3, Day 1 pre- and postdose, 4 h (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2020
  2. Study start11 Jun 2021
  3. Primary completion31 Jan 2025
  4. Study completion14 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
246 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04676477
Sponsor's protocol ID
U31402-A-U103
Other IDs
2020-003064-87
Status last verified
Oct 2026
First submitted
15 Dec 2020
Last updated
26 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HER3-DXd and Osimertinib in people with Non-Small Cell Lung Cancer (NSCLC), run by Daiichi Sankyo at 31 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in United States, Japan, South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: Incidence of Dose-limiting Toxicities (DLT), Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI) (time frame: From signing of informed consent form up to 40 days (+7 days) after the last dose of study drugs, up to approximately 9 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.

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