Hyperprogression in PD-L1 50% NSCLC: a Biomarker Guided Phase 2 Trial
Status:
NOT_YET_RECRUITING
Trial end date:
2030-06-01
Target enrollment:
Participant gender:
Summary
In metastatic NSCLC patients with PD-L1 expression 50%, a circulating immature (CD10-) LDNs level of 30.5% confers a high risk of hyperprogression (HPD) with first line single-agent immune-checkpoint inhibitors (SA-ICI). HPD is defined as a tumor growth rate (TGR) delta 50% between pre-treatment and post-treatment, and/or a TGR ratio 2. The combination of platinum-based chemotherapy (PCT) with ICI in this setting could prevent the occurrence of HPD and ultimately improve survival outcomes.
This randomized, multicentric, open-label, phase 2 trial will include patients with stage IV NSCL, without targetable oncogene drivers, PD-L1 TPS50%, and measurable disease on two CT scans performed before randomization. Participants will be randomized 1:1 to SA-ICI or ICI+PCT. Radiological evaluation will be performed by CT-scan at 6-8 weeks and subsequently according to the local investigators' schedule.
In the SA-ICI arm, ICI regimen will include cemiplimab. In the PCT+ICI arm, PCT regimens will include both carboplatin or cisplatin + pemetrexed (for non-squamous histology) or paclitaxel (for squamous histology) in combination with cemiplimab.
PCT will be administered for three cycles. In case of stable disease or partial response according to RECIST v.1.1, cemiplimab will be performed as monotherapy from the third cycle until disease progression or unacceptable toxicity. If progression according to RECIST v.1.1 or HPD after three cycles of PCT+ICI, patients will be treated with standard second line therapy as local standard of care.
Phase:
PHASE2
Details
Lead Sponsor:
Universit Vita-Salute San Raffaele
Collaborator:
Istituto Di Ricerche Farmacologiche Mario Negri
Treatments:
Carboplatin cemiplimab Cisplatin Drug Therapy Paclitaxel Pemetrexed