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Hyperprogression in PD-L1 ≥ 50% NSCLC: a Biomarker Guided Phase 2 Trial

NCT07274384 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 74

Last updated 2025-12-10

No results posted yet for this study

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 TPS≥50%, 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.

Conditions

  • NSCLC (Non-small Cell Lung Cancer)
  • Hyperprogression

Interventions

COMBINATION_PRODUCT

chemotherapy plus cemiplimab

Combination of platinum-based chemotherapy (PCT) with ICI. PCT regimens will include both carboplatin or cisplatin plus pemetrexed (for non-squamous histology) or paclitaxel (for squamous histology) in combination with cemiplimab. PCT will be administered for three cycles.

DRUG

Cemiplimab

single-agent immune-checkpoint inhibitors

Sponsors & Collaborators

  • Istituto Di Ricerche Farmacologiche Mario Negri

    collaborator OTHER

  • Università Vita-Salute San Raffaele

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-01-01
Primary Completion
2029-12-31
Completion
2030-06-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07274384 on ClinicalTrials.gov