Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)
- Men or women ≥20 years old in Japan, ≥18 years old in the United States on the day of signing the informed consent form (for the other countries, local regulatory requirements to consent should be followed)
- 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, RET, MET, 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, 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 advanced/metastatic disease
- Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with 1120 mg durvalumab Q3W): Has not received immune checkpoint inhibitor (ICI) including PD-1/PD-L1, PD-L2, CTLA-4, 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 1120 mg durvalumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2 Q3W): ICI naïve and has not been treated with systemic anticancer therapy for advanced or metastatic NSCLC.
- Willing and able to undergo a mandatory tumor biopsy. There is no requirement for PD-L1 protein expression for inclusion.
- 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 adverse events with prior immunotherapy treatment
- 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 allogenic organ transplantation
- Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or durvalumab, and carboplatin or cisplatin for participants to be enrolled in those relevant cohorts)
- Uncontrolled or significant cardiac disease
- 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 illnesses.
- Has a history of malignancy, other than NSCLC, except (a) adequately resected nonmelanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid tumors curatively treated, with no evidence of disease for ≥3 years.
- Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade ≤1 or baseline
The primary objective of this study will assess the safety and tolerability of datopotamab
deruxtecan (Dato-DXd) in combination with durvalumab with or without 4 cycles of platinum
chemotherapy in participants with advanced or metastatic NSCLC who have either been
previously treated or are treatment naïve in a metastatic setting.
Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with
1120 mg fixed dose of durvalumab, with or without 4 cycles of platinum chemotherapy in 6
study cohorts. This study will be conducted sequentially and dose escalation will occur
according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0
mg/kg) and from 2-drug combination (Dato-DXd and durvalumab) to 3-drug combination regimen
(Dato-DXd, durvalumab, and carboplatin or cisplatin).
Trial Phase Phase I
Trial Type Treatment
Daiichi Sankyo, Inc.
- Primary ID DS1062-A-U104
- Secondary IDs NCI-2021-02317, 2021-000274-28
- Clinicaltrials.gov ID NCT04612751