Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)
PHASE3ACTIVE_NOT_RECRUITING
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).
Study details:
The primary objectives of the study are Progression Free Survival (PFS) and Overall Survival (OS) as first line therapy in participants with programmed death-ligand 1 (PD-L1) TPS \<50% and advanced or metastatic NSCLC without actionable genomic alternations. Eligible participants will be randomized in a 1:1:1 ratio to a) Dato-DXd plus pembrolizumab plus platinum; b) Dato-DXd plus pembrolizumab; or c) pembrolizumab plus pemetrexed plus platinum. Platinum therapy will be either carboplatin or cisplatin at investigator discretion.
The study will be divided into three periods: Screening Period (including tissue screening), Treatment Period, and Follow-up Period.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- 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.
- 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).
- Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of six 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.
- 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.
- 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.
- Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.
Exclusion criteria
- Has received prior systemic treatment for advanced/metastatic NSCLC.
- Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC): Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I, TROP2-targeted therapy, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137), 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.
- 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.
- 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).
- Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including: 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), Myocardial infarction within 6 months prior to Cycle 1 Day 1, History of a serious cardiac arrhythmia requiring treatment, Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1, Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization, 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, 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).
- 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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE3
Study ID
NCT05555732
Intervention or treatment
DRUG: Datopotamab Deruxtecan
DRUG: Pembrolizumab
DRUG: Pemetrexed
DRUG: Carboplatin
DRUG: Cisplatin
Conditions
- Metastatic Non Small Cell Lung Cancer
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Research sites nearby
Closest Location:
CRSA/ St Andrews Hospital
Select from list below to view details:
CRSA/ St Andrews Hospital
Adelaide, Australia
Flinders Medical Centre (Fmc)
Bedford Park, Australia
PSEHOG (Peninsula and South Eastern Haematology and Oncology Group)
Frankston, Australia
St George Public Hospital
Kogarah, Australia
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Who is running the clinical trial?
DS
Daiichi Sankyo
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Dato-DXd + Pembrolizumab + Platinum Chemotherapy
| Drug: Datopotamab Deruxtecan, Drug: Pembrolizumab, Drug: Carboplatin, Drug: Cisplatin |
EXPERIMENTAL: Dato-DXd + Pembrolizumab
| Drug: Datopotamab Deruxtecan, Drug: Pembrolizumab |
ACTIVE_COMPARATOR: Pembrolizumab + Pemetrexed + Platinum Chemotherapy
| Drug: Pembrolizumab, Drug: Pemetrexed, Drug: Carboplatin, Drug: Cisplatin |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival Based on Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization until disease progression or death (whichever occurs first), up to approximately 29 months |
| Overall Survival in Participants in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | Overall Survival (OS) is defined as the time from randomization to death due to any cause. | From randomization until disease progression or death (whichever occurs first), up to approximately 57 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate by Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization until disease progression or death (whichever occurs first), up to approximately 29 months |
| Progression-free Survival by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization until disease progression or death (whichever occurs first), up to approximately 29 months |
| Objective Response Rate by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization until disease progression or death (whichever occurs first), up to approximately 29 months |
| Duration of Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | 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 29 months |
| Time to Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization to date of first objective response (CR or PR), up to approximately 29 months |
| Disease Control Rate by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | From randomization until disease progression or death (whichever occurs first), up to approximately 29 months |
| Progression-free Survival 2 in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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 | From randomization until disease progression or death (whichever occurs first), up to approximately 57 months |
| Time to Deterioration in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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). | From randomization until disease progression or death (whichever occurs first), up to approximately 57 months |
| Number of Participants With Treatment-emergent Adverse Events (TEAE) in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC) | 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. | Up to 57 months |
| 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 Dato-DXd in combination with pembrolizumab will be assessed. | Baseline and up to 57 months |
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References
Clinical Trials Gov: Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in 1L Non-Small Cell Lung Cancer (TROPION-Lung07)Other trials to consider
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