This study is in progress, not accepting new patients

Phase III, Open-label, First-line Study of Dato-DXd in Combination With Durvalumab and Carboplatin for Advanced NSCLC Without Actionable Genomic Alterations

a study on Non-Small Cell Lung Cancer Lung Cancer

Summary

Eligibility
for people ages 18-130 (full criteria)
Location
at UC Irvine
Dates
study started
study ends around
Principal Investigator
by Misako Nagasaka (uci)

Description

Summary

This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).

Official Title

A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)

Details

Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.

The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:

  1. PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
  2. OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
  3. PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
  4. OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC

Keywords

NSCLC, Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC), Datopotamab deruxtecan (Dato-DXd, Datroway), Durvalumab (Imfinzi), Carboplatin, Chemotherapy, Antibody-Drug Conjugate (ADC), Trophoblast cell surface protein 2 (TROP2), Non-Small-Cell Lung Carcinoma, durvalumab, pembrolizumab, Cisplatin, Pemetrexed, Paclitaxel, Datopotamab deruxtecan, Dato-DXd + Durvalumab + Carboplatin, Histologic-specific therapy

Eligibility

For people ages 18-130

Inclusion:

  • Participants ≥ 18 years at screening
  • Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
  • Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).

Testing is not required for tumors with squamous histology, with exceptions.

  • ECOG PS of 0 or 1
  • Archival tumour tissue
  • Has adequate bone marrow reserve and organ function within 7 days before randomization

Exclusion:

  • Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
  • History of another primary malignancy with exceptions
  • Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
  • Spinal cord compression or clinically or radiologically active brain metastases
  • History of leptomeningeal carcinomatosis.
  • Known active or uncontrolled hepatitis B or C virus infection.
  • Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
  • Clinically significant corneal disease
  • History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.

Locations

  • Research Site
    Fountain Valley California 92708 United States
  • Research Site
    Los Angeles California 90017 United States
  • Research Site
    Orange California 92868 United States

Lead Scientist at University of California Health

  • Misako Nagasaka (uci)
    Associate Clinical Professor, Medicine, School of Medicine. Authored (or co-authored) 244 research publications

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
AstraZeneca
ID
NCT05687266
Phase
Phase 3 research study
Study Type
Interventional
Participants
About 1350 people participating
Last Updated