Overcoming Resistance to Immunotherapy Combining Gemcitabine With Ivonescimab in Advanced NSCLC
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSwiss Cancer Institute
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
Written informed consent according to Swiss law and ICH GCP E6 regulations before registration and prior to any trial specific procedures including patient screening.
Confirmed squamous or non-squamous mNSCLC stage IIIB-IV (based on 9th edition Tumor-Node-Metastasis (TNM) classification of lung cancers with disease recurrence or progression during or after one or more prior immunotherapy or CIT regimens for metastatic disease.
Previous CNS-directed therapy has been completed at least 4 weeks prior to treatment start.
No evidence of progression after completion of CNS-directed therapy as ascertained by clinical examination and brain imaging with Magnetic Resonance Imaging (MRI) or CT.25
Disqualifiers
Symptomatic brain metastases.
Prior treatment with gemcitabine in combination with immunotherapies.
Tumor progression within the first 8 weeks from start of first-line treatment.
Activating EGFR or ALK mutations.
Trial design
Design model
Single group
Treatments tested in this trial
Gemcitabine + Ivonescimab
DrugThe 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.
Treatment groups
47 Participants
are divided into 1 treatment groupGroup A: Gemcitabine + Ivonescimab in Advanced NSCLC Resistant to ImmunotherapyExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Objective response rate (ORR) according to RECIST v1.1
ORR according to RECIST v1.1 is defined as the proportion of patients, whose best overall response is either complete response (CR) or partial response (PR) achieved before disease progression according to RECIST v1.1 or start of a subsequent anti-cancer treatment whichever occurs first. Patients with CR or PR as best observed response will be considered as success; otherwise as failures for this endpoint. Patients without any tumor assessment or with non-evaluable response (NE) during trial treatment will be considered as failures for this endpoint. The primary analysis will be based on the results from the Independent Response Review.
Time frame
At the end of trial treatment, up to 2 years from registration.Secondary outcomes
1
Duration of response (DoR) according to RECIST v1.1
DoR according to RECIST v1.1 is defined as the time from the first documentation of CR or PR (whichever occurs first) until disease progression according to RECIST v1.1 or death due to any cause. Patients not experiencing an event at the time of analysis and those starting a subsequent anticancer treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent anti-cancer treatment, if any. This endpoint will be calculated for the subgroup of patients achieving CR or PR. The analysis of this endpoint will be based on the independent response review.
Time frame
From first response up to 2 years from treatment start.2
Progression-free Survival (PFS) according to RECIST v1.1
PFS according to RECIST v1.1 is measured as the time from the first dose of ivonescimab/gemcitabine until disease progression according to RECIST v1.1 or death due to any cause. Patients not experiencing an event at the time of analysis and those receiving a subsequent anti-cancer treatment without an event will be censored at the date of their last available tumor assessment before starting subsequent anti-cancer treatment, if any. The analysis of this endpoint will be based on the independent response review.
Time frame
From first dose of ivonescimab/gemcitabine, up to 2 years from treatment start.Sponsors and contacts
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Source ClinicalTrials.gov