A Study to Evaluate DS-1062a Combined with Pembrolizumab in Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations


NCT ID: NCT04526691
Sponsor Protocol Number: DS1062-A-U102

About this study

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 who have had previously treated with platinum-based therapy with or without prior immunotherapy.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Histologically confirmed at diagnosis of NSCLC that:

- Is advanced or metastatic.

- Participants with non-squamous histology must have documented negative test
results for actionable EGFR and ALK genomic alterations. Participants with
squamous histology are required to undergo testing for EGFR and ALK genomic
alterations if they are nonsmokers or under the age of 40 years.

- Has either documented negative or unknown test results for actionable genomic
alterations in ROS1, NTRK, BRAF, RET, MET, or other actionable oncogenic driver

- Participants with tumors that harbor KRAS mutations are eligible for this study.

- Participants with non-actionable genomic alterations in EGFR, ALK, ROS1, NTRK,
BRAF, RET, MET, or other kinases are eligible for the study.

- Documentation of radiological disease progression while on or after receiving the most
recent treatment regimen, if any, for advanced or metastatic NSCLC.

- Must meet the following prior therapy requirements for advanced or metastatic NSCLC:

- Dose escalation (all cohorts): Has received ≤2 lines of prior anticancer therapy
for locally advanced or metastatic NSCLC.

- Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
200 mg fixed dose of pembrolizumab): Has not received PD-1/PD-L1, PD-L2, CTLA-4
directed immunotherapy and may or may not have been treated with systemic
chemotherapy for advanced or metastatic NSCLC.

- Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
200 mg fixed dose of pembrolizumab and 4 cycles of AUC 5 carboplatin or cisplatin
75 mg/m^2): Has not been treated with systemic anticancer therapy for advanced or
metastatic NSCLC.

- 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.

- Is not a candidate for surgical resection or chemoradiation with curative intent.

Exclusion Criteria:

- Experienced grade 3 or higher immune-related adverse events (AEs) with prior treatment
of anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 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, OX 40, CD137).

- Received a live vaccine within 30 days prior to the first dose of study treatment.

- Active, known, or suspected autoimmune disease.

- Concomitant use of chronic systemic (IV or oral) corticosteroids or other
immunosuppressive medications, except for managing AEs.

- 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

- History of another primary malignancy (beyond NSCLC) except for:

- Malignancy treated with curative intent and with no known active disease for ≥3

- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease.

- Adequately treated carcinoma in situ without evidence of disease.

- Participants with a history of prostate cancer (tumor/node/metastasis stage) of
Stage ≤T2cN0M0 without biochemical recurrence or progression.

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