Study of DS-1062a with or without Pembrolizumab in Advanced or Metastatic Non-small Cell Lung Cancer without Actionable Genomic Alterations
- Conditions
- Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-002555-10-GR
- Lead Sponsor
- Daiichi Sankyo, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 740
Subjects must meet all of the following criteria to be eligible for randomization into the study:
1. Sign and date the Tissue Screening and Main ICFs, prior to the start of any study-specific qualification procedures.
2. Adults =18 years or the minimum legal adult age (whichever is greater) at the time of informed consent. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is >18 years old.)
3. Histologically documented NSCLC that meets all of the following criteria:
a. Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition).
b. Documented negative test results for EGFR, ALK, and ROS1 actionable genomic alterations based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are not available, subjects are required to undergo testing performed locally for these genomic alterations.
c. No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other actionable driver kinases with locally approved therapies. (Testing for genomic alterations besides EGFR, ALK, and ROS1 is not required prior to enrollment.) Subjects with squamous NSCLC are only required to
undergo EGFR, ALK, and ROS1 testing if they have no history of tobacco
smoking or were diagnosed with NSCLC at <40 years of age. Subjects
whose tumors harbor KRAS mutations are eligible for the study.
4. Has provided a formalin-fixed tumor tissue sample (minimum of 10 [preferably 15] × 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.
5. Tumor has high PD-L1 expression (TPS =50%) as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of 6 slides).
6. Has an adequate treatment washout period before Cycle 1 Day 1 as defined in protocol Section 5.1.
7. Measurable disease based on local imaging assessment using RECIST Version 1.1 (see Section 10.4 of the protocol).
8. Has left ventricular ejection fraction (LVEF) =50% by either an echocardiogram (ECHO) or multigated acquisition scan (MUGA) within 28 days before randomization.
9. ECOG PS of 0 or 1 at screening.
10. Has a life expectancy of at least 3 months.
11. Adequate bone marrow function within 7 days before randomization as defined in protocol Section 5.1.
12. If the subject is a female of childbearing potential, she must not be pregnant, breastfeeding or intend to become pregnant during the study; she must also have a negative serum pregnancy test at screening and must be willing to use highly effective birth control (as detailed in protocol Section 10.3.4) or avoid heterosexual intercourse upon randomization, during the Treatment Period, for 7 months following the last dose of Dato-DXd, and for 4 months following the last dose of pembrolizumab, whichever occurs later. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
13. If male, the subject must be sur
Subjects who meet any of the following criteria will be disqualified from entering the study:
1. Has received prior systemic treatment for advanced or metastatic NSCLC.
2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting:
a. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
b. TROP2-targeted therapy.
c. Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti-PD-ligand 2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
d. Any other immune checkpoint inhibitors.
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/metastatic disease.
3. Has spinal cord compression or active and untreated central nervous system (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 4 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 computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator should consider delay of study treatment to document stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of all screening activity may be required).
4. Has received prior radiotherapy =4 weeks of start of study intervention or more than 30 Gy to the lung within 6 months of Cycle 1 Day 1. Subjects must have recovered from all radiationrelated toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 2-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
5. History of another primary malignancy (beyond NSCLC) except for:
- Malignancy treated with curative intent and with no known active disease =3 years before the first dose of study treatment and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Subjects with a history of prostate cancer (tumor/node/metastasis stage) of Stage =T2cN0M0 without biochemical recurrence or progression and who in the opinion of the investigator are not deemed to require active intervention.
6. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, orhas suspected ILD/pneumonitis that cannot be ruled out by imaging
at screening.
7. Clinically severe pulmonary compromise 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 arthrit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method