RecruitingPhase 2NCT07158489

Overcoming Resistance to Immunotherapy Combining Gemcitabine With Ivonescimab in Advanced NSCLC

Protocol SAKK 18/ 25 Overcoming Resistance to Immunotherapy Combining Gemcitabine With Ivonescimab in Advanced NSCLC Progressing on Immune Checkpoint Inhibitors: A Multicenter, Single-arm, Open-label Phase II Trial (ORIGIN2)

Sponsor

Swiss Cancer Institute

Enrollment

47 participants

Start Date

Aug 21, 2026

Study Type

INTERVENTIONAL

Conditions

NSCLC NSCLC (Advanced Non-small Cell Lung Cancer)

Summary

This Phase II clinical trial (investigates the efficacy of combining gemcitabine, a chemotherapy agent, with ivonescimab, a bispecific PD-1/VEGF antibody, in patients with advanced non-small cell lung cancer (NSCLC) who have experienced disease progression following chemoimmunotherapy (CIT). Lung cancer remains the leading cause of cancer-related death globally, and treatment options after CIT failure are limited. Gemcitabine has demonstrated immunostimulatory properties, including enhanced T-cell infiltration and reduced immunosuppressive cell populations, which may synergize with immune checkpoint inhibitors. Ivonescimab targets both PD-1 and VEGF pathways, potentially enhancing antitumor immune responses and inhibiting tumor angiogenesis. The trial aims to evaluate the objective response rate (ORR) according to RECIST v1.1 criteria. The combination therapy is expected to offer a novel and effective treatment strategy for patients with relapsed NSCLC, addressing a significant unmet medical need.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This clinical trial is studying a drug called Gemcitabine + Ivonescimab for people with nsclc and nsclc (advanced non-small cell lung cancer). The study is currently recruiting participants at 7 locations. People eligible for this study include aged 18 Years and older.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGGemcitabine + Ivonescimab

The trial combines two Investigational Medicinal Products (IMPs): * Gemcitabine, either alone or in combination regimens, is the standard of care (SoC) for several solid tumors, such as advanced or metastatic non-small cell lung cancer (mNSCLC). * Ivonescimab is developed for cancer immunotherapy. Ivonescimab binds to human vascular endothelial growth factor (VEGF) which is involved in tumor angiogenesis, and to human programmed cell death 1 (PD-1) that is a cell surface receptor expressed primarily on activated T cells and acts to inhibit their activation.