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TROPION-10 (JCP159)

  • Writer: JGH CRP
    JGH CRP
  • Nov 8, 2024
  • 3 min read

A Phase III, Randomised, Open-label, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig (AZD2936) or Rilvegostomig Monotherapy Versus Pembrolizumab Monotherapy for the First-line Treatment of Participants With Locally-advanced or Metastatic Non-squamous NSCLC With High PD-L1 Expression (TC ≥ 50%) and Without Actionable Genomic Alterations

Population: NSCLC With High PD-L1 Expression


Line of therapy: 1L


Intervention: Dato-DXd + Rilvegostomig (AZD2936) VS. Rilvegostomig Monotherapy vs. Pembrolizumab Monotherapy


Key Inclusion Criteria

  1. Histologically or cytologically documented non-squamous NSCLC.

  2. Stage IIIB or IIIC or Stage IV metastatic NSCLC not amenable to curative surgery or definitive chemoradiation at the time of randomisation. Participants must not have received prior chemotherapy or other systemic therapy for Stage IIIB, IIIC or IV NSCLC.

  3. Absence of sensitising EGFR mutations (including, but not limited to, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), and ALK and ROS1 rearrangements.

    Note: Participants whose tumours harbour KRAS mutations are eligible for the study and EGFR and ALK testing for them is not required. If local testing is not available, prospective central testing will be offered in a Sponsor-designated central laboratory.

  4. Absence of documented tumour genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes (eg, NTRK, BRAF (p.V600E), RET, MET, etc) for which there are locally-approved targeted first-line therapies.

  5. ECOG 0 or 1, with no deterioration over the previous 2 weeks prior to the first dose of study intervention.

  6. Minimum life expectancy of 12 weeks.

  7. Provision of acceptable FFPE tumour sample from a lesion not previously irradiated. All participants must be able to provide an available FFPE tumour sample taken ≤ 3 months prior to the start of

    screening or to undergo a fresh tumour biopsy during screening for analysis. Note: Specimens from metastatic bone lesions are unacceptable unless there is a significant soft tissue component.

  8. Known tumour PD-L1 expression status defined as TC ≥ 50%, confirmed by central laboratory using either an FFPE tumour sample collected ≤ 3 months prior to the start of screening or an FFPE tumour sample collected during the screening period.

  9. Prior to the availability of the TROP2 assay, participants must provide tumour material for retrospective testing to be eligible for the study. Once the VENTANA TROP2 IHC + QCS CTA is available in a Sponsor-designated central laboratory for use in the study, a known central TROP2 status must be available prior to randomisation.

  10. At least one lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline with CT or MRI and is suitable for accurate repeated measurements

  11. Adequate bone marrow reserve and organ function within 7 days before the first dose of study intervention


Key Exclusion Criteria

  1. Any evidence of diseases (such as severe or uncontrolled systemic diseases, including active bleeding diseases, active infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations, or significant cardiac conditions), or history of allogenic organ transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.

  2. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention

    and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer (basal cell carcinoma of the skin or squamous cell carcinoma of the skin) and curatively treated in situ disease.

  3. Squamous cell histology, or predominantly squamous cell histology NSCLC; mixed small-cell lung cancer; NSCLC histology, sarcomatoid variant. Note: Rare subtypes (NUT carcinoma, thoracic SMARCA4-deficient undifferentiated tumour, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma) and lung neuroendocrine tumours (NETs) are excluded.

  4. Persistent toxicities caused by previous anti-cancer therapy (see also Exclusion Criterion 22), excluding alopecia, not yet improved to Grade ≤ 1 or baseline.

  5. Active or prior documented autoimmune or inflammatory disorders, including inflammatory bowel disease

  6. Participants who have received prior systemic therapy for advanced/metastatic NSCLC. Note: Participants who have received prior platinum containing adjuvant, neoadjuvant chemotherapy, or definitive radiation/chemoradiation for early stage disease are eligible, provided that progression has occurred > 12 months from the last dose of chemotherapy or radiation/chemoradiation.

  7. Current or prior use of immunosuppressive medication within 14 days before the first dose of study intervention

  8. Palliative radiation with a limited field of radiation within ≤ 2 weeks or with wide field of radiation to chest (or to more than 30% of the bone marrow) within ≤ 4 weeks before the

    first dose of study intervention or had radiation-related toxicities requiring corticosteroids.

  9. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within ≤ 3 weeks of randomisation or an anticipated need for major surgery during the study


Sponsor: AstraZeneca



CRP PI: Dr. J. Agulnik


Status: Open to accrual

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