Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02)

• Status: Recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will assess safety and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab with or without platinum chemotherapy in participants with advanced or metastatic non-small cell lung cancer.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Daiichi Sankyo, Inc.
• Collaborators: AstraZeneca; Merck Sharp & Dohme Corp.
• Treatments: Carboplatin; Pembrolizumab

Criteria

Inclusion Criteria:

• 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).

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

• 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.

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 transplantation.

• 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 non-melanoma skin cancer, (b) curatively treated in situ disease, or (c) other solid tumors curatively treated, with no evidence of disease for ≥3 years.