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Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC

NCT04686305

Description:

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with chemotherapy in patients with HER2 positive advanced and metastatic non-small lung cancer. The efficacy will be also analyzed as a secondary endpoint.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase Ib Study of the Safety of T-DXd and Durvalumab With Chemotherapy in Advanced or Metastatic HER2+ Non-squamous NSCLC
  • Official Title: A Phase Ib Multicenter, Open-label Dose-escalation Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Durvalumab in Combination With Cisplatin, Carboplatin or Pemetrexed in First-line Treatment of Patients With Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) and Human Epidermal Growth Factor Receptor 2 Overexpression (HER2+) (DESTINY-Lung03)

Clinical Trial IDs

  • ORG STUDY ID: D967YC00001
  • NCT ID: NCT04686305

Conditions

  • Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Trastuzumab deruxtecanDS-8201a, T-DXdArm 1: T-DXd, Durvalumab and Cisplatin
DurvalumabMEDI4736Arm 1: T-DXd, Durvalumab and Cisplatin
CisplatinArm 1: T-DXd, Durvalumab and Cisplatin
CarboplatinArm 2: Arm 2: T-DXd, Durvalumab and Carboplatin
PemetrexedArm 3: T-DXd, Durvalumab and Pemetrexed

Purpose

DESTINY-Lung03 will investigate the safety and tolerability of trastuzumab deruxtecan in combination with chemotherapy in patients with HER2 positive advanced and metastatic non-small lung cancer. The efficacy will be also analyzed as a secondary endpoint.

Detailed Description

      This is a dose escalation study by design, allowing the assessment of safety, tolerability
      and recommended dose levels of the combination of T-DXd and durvalumab plus cisplatin,
      carboplatin or pemetrexed. Expansions on any recommended dose level may take place to study
      preliminary efficacy as well.

      The target population of interest are patients with advanced or metastatic non-small cell
      lung cancer and HER2 overexpression who are treatment naïve and have measurable disease by
      RECIST criteria and ECOG PS of 0 to 1.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1: T-DXd, Durvalumab and CisplatinExperimentalT-DXd, Durvalumab and Cisplatin
  • Trastuzumab deruxtecan
  • Durvalumab
  • Cisplatin
Arm 2: Arm 2: T-DXd, Durvalumab and CarboplatinExperimentalT-DXd, Durvalumab and Carboplatin
  • Trastuzumab deruxtecan
  • Durvalumab
  • Carboplatin
Arm 3: T-DXd, Durvalumab and PemetrexedExperimentalT-DXd, Durvalumab and Pemetrexed
  • Trastuzumab deruxtecan
  • Durvalumab
  • Pemetrexed
Arm 4: T-DXd and DurvalumabExperimentalT-DXd and Durvalumab
  • Trastuzumab deruxtecan
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented locally advanced/metastatic non-squamous NSCLC

          -  Patients must have tumors that lack activating EGFR mutations, EML4-ALK fusion, and
             ROS-1 mutation

          -  Patients must be treatment- naïve for locally advanced or mNSCLC and medically fit to
             receive first-line treatment. Prior adjuvant, neo adjuvant therapies are permitted if
             progression has occurred > 12 months from the end of last therapy

          -  HER2+ (IHC 3+ or IHC 2+) status as determined by central review of tumor tissue

          -  WHO / ECOG performance status of 0 or 1

          -  Has a measurable target disease assessed by the investigator using RECIST 1.1

          -  Has a protocol defined adequate organ and bone marrow functions

        Exclusion criteria:

          -  Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current
             ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at
             screening

          -  Lung-specific intercurrent clinically significant illnesses including, but not limited
             to, any underlying pulmonary disorder and prior pneumonectomy

          -  Active primary immunodeficiency known HIV infection, or active hepatitis B or C
             infection

          -  Active infection including tuberculosis and uncontrolled infection requiring IV
             antibiotics, antivirals, or antifungals

          -  Spinal cord compression or clinically active central nervous system metastases,
             defined as untreated and symptomatic, or requiring therapy with corticosteroids or
             anticonvulsants to control associated symptoms

          -  Medical history of myocardial infarction within 6 months before treatment assignment,
             symptomatic CHF (New York Heart Association Class II to IV), clinically important
             cardiac arrhythmias, or a recent (< 6 months) cardiovascular event including stroke

          -  A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal
             shunt, or CART
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of AEs and SAEs
Time Frame:Safety will be assessed for approximately 20 months from informed consent
Safety Issue:
Description:Occurrence of AEs and SAEs graded according to NCI CTCAE v5.0

Secondary Outcome Measures

Measure:Confirmed Objective Response Rate (ORR)
Time Frame:An average of approximately 12 months
Safety Issue:
Description:Confirmed ORR per RECIST 1.1 is the percentage of patients with Complete Response or Partial Response that is subsequently confirmed, based on investigator assessment
Measure:Duration of Response (DoR)
Time Frame:An average of approximately 12 months
Safety Issue:
Description:DOR is defined as the time from the date of first documented response until the date of documented progression or death, based on RECIST assessment
Measure:Disease Control Rate (DCR)
Time Frame:An average of approximately 12 months
Safety Issue:
Description:DCR is the percentage of patients who have a best overall response of complete response (CR) or partial response (PR) or stable disease (SD), based on RECIST assessment
Measure:Progression-free survival (PFS)
Time Frame:An average of approximately 12 months
Safety Issue:
Description:PFS is the time from first dose of study treatment until the date of objective disease progression or death, based on RECIST assessment
Measure:Overall survival (OS)
Time Frame:An average of approximately 20 months
Safety Issue:
Description:OS is the time form the date of first dose of study treatment until death due to any cause
Measure:Pharmacokinetics (PK) assessed by the serum concentration of T-DXd, total anti-HER2 antibody, and MAAA-1181 in all arms
Time Frame:An average of approximately 20 months
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for T-DXd, total anti-HER2 antibody and MAAA-1181a
Measure:Pharmacokinetics (PK) assessed by the serum concentration of durvalumab in study arms including T-DXd in combination with durvalumab
Time Frame:An average of approximately 20 months
Safety Issue:
Description:Individual patient data and descriptive statistics will be provided for serum concentration data at each time point for durvalumab, including T-DXd in combination with durvalumab
Measure:The immunogenicity of T-DXd and durvalumab assessed by the presence of ADAs for T-DXd and durvalumab
Time Frame:An average of approximately 20 months
Safety Issue:
Description:Individual participant data and descriptive statistics will be provided for data at each time point for each dose level for T-DXd and durvalumab.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • HER2+
  • DS-8201a
  • T-DXd
  • Trastuzumab Deruxtecan
  • Locally advanced non-squamous NSCLC
  • Metastatic non-squamous NSCLC
  • Non-small cell lung cancer

Last Updated

January 11, 2021