Phase II Study of Upfront SRT Plus Ivonescimab/Chemotherapy vs Ivonescimab/Chemotherapy in NSCLC Brain Mets

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Study ID
NCT07234877
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ivonescimab — DRUG
    ivonescimab iv at 20 mg/kg every 3 weeks
  • Carboplatin — DRUG
    For adenocarcinoma : Carboplatin area under the curve of 5 mg/mL/min (AUC 5) IV with pemetrexed 500 mg/m2 IV on day 1 every 21 days (Q3W) for 4 cycles
  • Pemetrexed — DRUG
    For adenocarcinoma : Carboplatin area under the curve of 5 mg/mL/min (AUC 5) IV with pemetrexed 500 mg/m2 IV on day 1 every 21 days (Q3W) for 4 cycles
  • Paclitaxel — DRUG
    For squamous cell carcinoma: Carboplatin AUC 6 mg/mL/min IV/ paclitaxel IV 200 mg/m2 on day 1 every 21 days (Q3W) for 4 cycles (or 175 mg/m2 on D1 for Asian participant) Q3W for 4 cycles
  • Paclitaxel-albumin — DRUG
    For squamous cell carcinoma: Carboplatin AUC 6 mg/mL/min IV/ albumin-bound paclitaxel 100 mg/m2 on D1, 8 and 15 Q3W for 4 cycles
  • Stereotactic Radiosurgery (SRS) or Fractionated Stereotactic Radiotherapy (FSRT) — RADIATION
    Patients will receive SRS/FSRT for all BM within ≤14 days from randomization, followed by 4 cycles of platinum-based chemotherapy combined with ivonescimab at 20 mg/kg every 3 weeks (Q3W). The systemic therapy should be initiated within 7 to 10 days after the end of SRS/FSRT but no earlier than 3 days after its completion. This will be followed by maintenance therapy with ivonescimab at 20 mg/kg plus pemetrexed (for patients with non-squamous NSCLC only) Q3W, for up to 2 years.

Study Details

This is a randomized, two-arm, comparative Phase II clinical trial designed to evaluate the difference in intracranial progression-free survival (iPFS) between two treatment strategies, assessed locally. Approximately 158 patients will be randomized in a 1:1 ratio. Will be included patients with pathology proven metastatic NSCLC without an actionable genomic alteration for which there is first line targeted treatment available and active asymptomatic brain metastasis (newly diagnosed or progressive). The primary objective is to compare iPFS between the two arms.

Key Dates

Start date
Nov 30, 2026
Status verified
Jun 2026
Primary completion
Jan 31, 2032
Completion
Apr 30, 2032

Study Design

Enrollment
158 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Sequencing arm
    Patients will receive SRS/FSRT for all BM within ≤14 days from randomization, followed by 4 cycles of platinum-based chemotherapy combined with ivonescimab at 20 mg/kg every 3 weeks (Q3W). The systemic therapy will be followed by maintenance therapy with ivonescimab at 20 mg/kg plus pemetrexed (for patients with non-squamous NSCLC only) Q3W, for up to 2 years.
  • Experimental: Systemic treatment alone arm
    Patients will receive 4 cycles of platinum-based chemotherapy combined with ivonescimab 20 mg/kg Q3W, followed by maintenance ivonescimab 20 mg/kg with pemetrexed (pemetrexed non-squamous only) Q3W for a maximum of 2 years.

Primary Outcome Measure

Intracranial progression-free survival based on local assessment using RANO-BM criteria [ Time Frame: First at week 6 and week 12 (±1 week) post-randomization. Then every 12 weeks (±2 weeks) until intracranial progression or study discontinuation. ]

Central Contacts

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