Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)

NCT05555732
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,170
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Lead sponsor
Daiichi Sankyo
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Start date
2023-01-11
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Number of sites
260
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Summary
This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab in combination with pemetrexed and platinum chemotherapy in participants with no prior therapy for advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
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Short title
Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)
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Official title
A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2031-05-11
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First posted
2022-09-27
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Registry last updated
2026-06-23
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Primary completion date
2029-05-11
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Start date
2023-01-11
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Participants
1,170
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Participant count basis
Estimated
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Planned participants
1,170
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Protocol amendments
3
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Randomisation ratio
1:1:1
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Number of sites
260
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Daiichi Sankyo
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05555732
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ClinicalTrials.gov ID
NCT05555732
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.

  2. Progression-free Survival Based on Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.

  3. Overall Survival in All Randomized Participants

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months

    Overall Survival (OS) is defined as the time from randomization to death due to any cause.

  4. Overall Survival in All Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months

    Overall Survival (OS) is defined as the time from randomization to death due to any cause.

  1. Objective Response Rate by Blinded Independent Central Review in All Randomized Participants

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1.

  2. Objective Response Rate by Blinded Independent Central Review in All Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1.

  3. Progression-free Survival by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1.

  4. Objective Response Rate by Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by the Investigator per RECIST Version 1.1.

  5. Duration of Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 43 months

    Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1.

  6. Time to Response by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization to date of first objective response (CR or PR), up to approximately 43 months

    Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1.

  7. Disease Control Rate by BICR and Investigator in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months

    Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1.

  8. Progression-free Survival 2 in Both All Randomized Participants and Randomized Participants who are TROP2 NMR positive

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months

    Progression-free Survival 2 (PFS2) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by local standard clinical practice

  9. Time to Deterioration

    Timeframe: From randomization until disease progression or death (whichever occurs first), up to approximately 76 months

    Time to Deterioration (TTD) is defined as the time from randomization to first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13).

  10. Number of Participants With Treatment-emergent Adverse Events (TEAE)

    Timeframe: Up to 76 months

    A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment.

  11. Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA

    Timeframe: Baseline and up to 76 months

    The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

Key Inclusion Criteria:

  1. Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
  2. Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is >18 years old).
  3. Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
  4. Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.
  5. Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criteria are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion.
  6. Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.

Key Exclusion Criteria:

  1. Has received prior systemic treatment for advanced/metastatic NSCLC.

  2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):

    1. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
    2. TROP2-targeted therapy
    3. Any anti-PD-1, anti-PD-L1, or anti-programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
    4. Any other ICIs Subjects who received adjuvant or neoadjuvant therapy other than those listed above are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced or metastatic disease.

  3. Has received a live vaccine within 30 days prior to the first dose of study treatment.

    Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.

    Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.

  4. Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).

  5. Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:

    1. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex (based on the 12-lead electrocardiogram [ECG] performed at screening).
    2. Myocardial infarction within 6 months prior to Cycle 1 Day 1.
    3. History of a serious cardiac arrhythmia requiring treatment
    4. Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
    5. Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
    6. New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
    7. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).

  6. Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.

Sources for eligibility
clinicaltrials.gov

  • Southern Cancer Center PcDaphne, United States
  • Ironwood Cancer and Research CentersChandler, United States
  • Arizona Oncology Associates, Pc - NahoaPrescott Valley, United States
  • Hoag Memorial Hospital PrebyterianNewport Beach, United States
  • Compassionate Cancer Care Medical GroupRiverside, United States
  • Sansum ClinicSanta Barbara, United States
  • Ronald Reagan UCLA Medical CenterSanta Monica, United States
  • UCHealth Memorial HospitalColorado Springs, United States
  • Florida Cancer Specialists - SouthFort Myers, United States
  • Cancer Specialist of North FloridaJacksonville, United States
  • Cancer Care Centers of Brevard, Inc.Palm Bay, United States
  • Woodlands Medical Specialists, PaPensacola, United States
  • Florida Cancer Specialists-NorthSt. Petersburg, United States
  • Emory University - Winship Cancer Institute WciAtlanta, United States
  • Illinois Cancer SpecialistsNiles, United States
  • American Oncology Partners of MarylandBethesda, United States
  • Maryland Oncology Heamtology P.A.Columbia, United States
  • Beth Israel Deaconess Medical CenterBoston, United States
  • Dana Farber Cancer Institute; Inv Drg Svc PharmBoston, United States
  • Dana Farber Cancer Institute At St. Elizabeth'S Medical CenterBrighton, United States
  • Dana Farber Brigham Cancer CenterFoxborough, United States
  • Dana Farber At Milford Regional Cancer CenterMilford, United States
  • Dana Farber/Bwcc in Affiliation With South Shore HospitalSouth Weymouth, United States
  • Astera Cancer CareEast Brunswick, United States
  • Regional Cancer Care Associates LLCHackensack, United States

And 235 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • MK-3475-E10
  • jRCT2061220066
  • 2022-500802-16-00
  • TROPION-Lung07
Sources for references
clinicaltrials.gov

Related records

Drugs (5)

Collaborators (2)

Lead sponsors (1)

Conditions (1)

Targets (6)