This study will assess safety and treatment activity of DS-1062a in combination with
pembrolizumab in participants with advanced or metastatic NSCLC without actionable genomic
alterations and who have been previously treated with at least 1 regimen of platinum-based
chemotherapy and at least 1 regimen of programmed cell death 1 (PD-1)/programmed cell death
ligand 1 (PD-L1)-directed immunotherapy, either in combination or sequentially. Participants
with a documents PD-L1 tumor proportion score of <1% must have been previously treated with
at least 1 regimen of platinum-based chemotherapy with or without PD-1/PD-L1 immunotherapy.
- Advanced or metastatic NSCLC, histologically confirmed at diagnosis of NSCLC,
documented negative test results for EGFR and ALK genomic alterations, and no known
genomic alterations in ROS1, NTRK, BRAF, or other driver oncogenes with approved
therapies (actionable genomic alterations).
- Documentation of radiological disease progression while on or after receiving the most
recent treatment regimen for advanced or metastatic NSCLC.
- Received at least 1 regimen of platinum-based chemotherapy and have at least 1 regimen
of PD 1/PD L1 directed immunotherapy, either in combination or sequentially.
Participants with a documented PD L1 TPS of <1% must have been previously treated with
at least 1 regimen of platinum-based chemotherapy with or without prior PD 1/PD-L1
- Willing and able to undergo a mandatory tumor biopsy.
- Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue
is available, for measurement of TROP2 expression levels or other biomarkers.
- Has adequate bone marrow reserve and organ function at baseline within 7 days prior to
Cycle 1 Day 1
- Experienced grade 3 or higher immune-related AE with prior treatment of anti-PD-1,
anti-PD-L1, or anti programmed cell death ligand 2 (PD L2) agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40,
- Received a live vaccine within 30 days prior to the first dose of study treatment.
- Active, known, or suspected autoimmune disease.
- Has a condition requiring systemic treatment with either corticosteroids (>10 mg daily
prednisone equivalent) or other immunosuppressive medications within 14 days of Cycle
1 Day 1.
- Prior organ transplantation, including allogeneic tissue or solid organ
- Has 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.
- History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required
steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be
ruled out by imaging at screening.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary
- Has other primary malignancies, except adequately resected non-melanoma skin cancer,
curatively treated in situ disease, or other solid tumors curatively treated, with no
evidence of disease for ≥3 years.