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

ConditionNon Small Cell Lung Cancer
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorEuropean Organisation for Research and Treatment of Cancer - EORTC

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 18 years or older

ECOG PS <= 2

Patients with pathology proven metastatic NSCLC without an actionable genomic alteration for which there is first line targeted treatment approved by EMA and recommended by the ESMO guidelines.

Asymptomatic or clinically symptomatic brain metastases defined as requiring a dose of steroids of maximum 4 mg equivalent dexamethasone per day for the last 7 days to control neurological symptoms. With the clinically oligosymptomatic further defined as having no indication for immediate localized brain therapy, including neurosurgery or radiotherapy. Patients with controlled seizures can be enrolled.

Disqualifiers

Patients with oligometastatic NSCLC who are scheduled to receive radical local treatment to extra-cranial sites.

Patients with contra-indications to brain MRI with gadolinium-based contrast agent.

Active auto-immune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

Patients with >30 Gy of chest radiation therapy within 6 months prior to randomization; non-thoracic radiation therapy >30Gy within 4 weeks prior to randomization, or palliative radiation therapy of ≤30 Gy within 7 days prior to randomization.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

Treatment groups

158 Participants
are divided into 2 treatment groups
Group A: Sequencing armExperimental treatment 6 interventions
Group B: Systemic treatment alone armExperimental treatment 5 interventions

Trial outcomes

Primary outcomes

1

Intracranial progression-free survival based on local assessment using RANO-BM criteria

Time interval between the date of randomization and the date of intracranial progression or neurological related death, whichever occurs first

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.

Secondary outcomes

1

Overall survival

Time frame
Overall survival is defined as the time interval between the date of randomization and the date of death from any cause, assessed up to 4 years
2

Intracranial PFS as per central review

Time frame
Intracranial PFS based on central assessment is defined as the time interval between the date of randomization and the date of intracranial progression or neurological related death, whichever occurs first, assessed up to 2 years
3

Intracranial overall response rate (icORR), based on RANO-BM criteria as per local assessment

Time frame
The overall icORR is defined as the time interval between the date of randomization and the date of intracranial response, assessed up to 2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

European Organisation for Research and Treatment of Cancer - EORTC

Lead sponsor

Summit Therapeutics

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: