Phase III Study of Datopotamab Deruxtecan Versus Docetaxel in Previously Treated TROP2-positive Advanced or Metastatic Non-squamous NSCLC Without Actionable Genomic Alterations (TROPION-Lung17)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Non-small Cell Lung Cancer (NSCLC)

Treatments: Drug: Docetaxel; Drug: Datopotamab deruxtecan (Dato-DXd)

Study type: Interventional

Funder types: Industry

Identifiers

NCT07291037

D763QC00001

2024-520101-39-00 (Other Identifier)

Details and patient eligibility

About

TROPION-Lung17 will measure the efficacy and safety of datopotamab deruxtecan (Dato-DXd) compared with docetaxel in patients with trophoblast cell surface protein 2 (TROP2) positive advanced or metastatic lung cancer without actionable genomic alterations (AGA).

Full description

TROPION-Lung17 is a phase III, 2-arm, randomised, open-label, multicentre study, assessing the efficacy and safety of Dato-DXd compared with docetaxel in participants with previously treated trophoblast cell surface protein 2 (TROP2) normalised membrane ratio (NMR) positive advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA), and to assess the clinical performance of the investigational in vitro diagnostic (IVD) device.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

- Pathologically documented Stage IIIB, IIIC, or Stage IV non-squamous non-small cell lung cancer (NSCLC) without actionable genomic alterations (AGA) at the time of randomisation and meets the criteria for NSCLC:

• Participants must have documented negative test results for EGFR (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), ALK, and ROS1 genomic alterations.

Note: If test results for EGFR, ALK, and ROS1 are not available, participants are required to undergo prospective testing performed centrally for these genomic alterations in a Sponsor-designated central laboratory.

• Has no known tumour genomic alterations in NTRK, BRAF V600, RET, MET exon 14 skipping, KRAS G12C, or HER2. Additionally, participants must not have known tumour genomic alteration of any other actionable driver oncogenes for which there are locally approved targeted first-line therapies.

Note: Participants whose tumours harbour BRAF (exception V600) or KRAS (exception G12C) mutations are eligible for the study.

• Prospectively assessed TROP2 NMR positive based on results from an appropriately validated investigational TROP2 RxDx device in a Sponsor- designated, regulatory compliant central laboratory.

  • Documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
  • Participants must have received platinum based chemotherapy (PBC) in combination with anti-programmed death-protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibody (mAb) as the only prior line of therapy or received PBC and anti-PD-1/anti-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy.
  • Provision of acceptable formalin fixed and paraffin embedded (FFPE) tumour sample for assessment of TROP2.
  • At least one lesion not previously irradiated that qualifies as a Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) target lesion (TL) at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for accurate repeated measurements.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  • Adequate bone marrow reserve and organ function within 7 days before randomisation.

Exclusion criteria

• Squamous, mixed NSCLC, or small cell lung cancer (SCLC) histology.
• NSCLC disease that is eligible for definitive local therapy alone.
• History of another primary malignancy other than NSCLC, except for malignancy treated with curative intent with no known active disease within 3 years before randomisation and of low potential risk for recurrence.
• Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring treatment with corticosteroids or anticonvulsants for at least 7 days prior to randomisation.
• Clinically significant corneal disease.
• Has active or uncontrolled hepatitis B or C virus infection.
• Known human immunodeficiency virus (HIV) infection that is not well controlled.
• Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals.
• History of ILD/pneumonitis, including radiation pneumonitis (apart from radiation pneumonitis that did not require steroids), or drug-induced ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. Examples of suspected ILD/pneumonitis by imaging include the presence of lung parenchymal fibrosis, such as combined pulmonary fibrosis and emphysema (CPFE), and any radiographic features consistent with interstitial lung abnormalities, including but not limited to, extensive ground glass opacities, reticular opacities, traction bronchiectasis, and honeycombing.
• Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrolment, severe asthma, severe COPD, restrictive lung disease, symptomatic pleural effusion, etc).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Arm A: Datopotamab deruxtecan (Dato-DXd) monotherapy

Experimental group

Description:

Participants in the Dato-DXd monotherapy group will receive Dato-DXd as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Treatment:

Drug: Datopotamab deruxtecan (Dato-DXd)

Arm B: Docetaxel monotherapy

Active Comparator group

Description:

Participants in the docetaxel monotherapy group will receive docetaxel as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.

Treatment:

Drug: Docetaxel