Evaluation of the Value of [68Ga]Ga-PENTIXAFOR PET-CT in Patients With Metastatic Small Cell Lung Cancer (SCLC)

Small cell lung cancer (SCLC) accounts for approximately 15% of lung cancers, but remains a cancer with a poor prognosis, often detected at a metastatic stage and associated with a high rate of early recurrence.

Therapeutic options for unresectable SCLC are limited and essentially rely on first-line radiochemotherapy for limited disease or chemo-immunotherapy, possibly supplemented by radiotherapy, for extensive disease.

CXCR4 is a chemokine receptor that is highly expressed in this cancer. By targeting CXCR4 with [177Lu]Lu-PentixaTher or [90Y]Y-PentixaTher, patients with SCLC could benefit from a new type of treatment in this indication: Peptide Receptor Radionuclide Therapy (PRRT).

However, there is a need for a preliminary diagnostic study due to a lack of published data.

[68Ga]Ga-PentixaFor is an experimental compound that binds with high affinity to CXCR4 and appears to be a promising candidate for PET-CT imaging of SCLC. This initial step is crucial to confirm CXCR4 targeting by [68Ga]Ga-PentixaFor before considering PRRT with therapeutic radionuclides such as Lu-177 or Y-90 in future trials.

Inclusion criteria

• Written informed consent signed before performing any trial specific procedure.
• Male or female, age ≥ 18 years at time of study entry.
• Patient with histologically proven small cell lung carcinoma, inoperable, non-pre-treated.
• Metastatic disease documented by conventional imaging and/or [18F]FDG PET-CT with at least one metastatic measurable lesion (RECIST 1.1). Patients eligible for 1st line metastatic treatment.
• Availability of tissue material (primary lesion and/or metastatic site) to allow additional immunohistochemical studies.
• PS < 2.
• Consent to use a contraception method for at least 3 months after each administration of [68Ga]Ga-PentixaFor.
• Adequate Organ function confirmed by laboratory test results allowing for safe the [68Ga]Ga-PentixaFor administration.
• Life expectancy greater than 3 months.
• Patient has valid health insurance.
• Patient willing and able to comply with the protocol throughout the duration of the study, including during treatment and scheduled visits and examinations, including follow-up.

Exclusion criteria

• History of cancer in the 3 years prior to entry into the trial other than basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• History of anti-cancer treatments such as chemotherapy, radiotherapy or immunotherapy as well as other clinical trials for SCLC before the first [68Ga]Ga-PentixaFor PET-CT imaging.
• Inability to lie still for at least 1 hour, or known claustrophobia.
• Serious non-malignant disease (e.g., psychiatric, infectious, autoimmune, or metabolic) which may interfere with study objectives or patient safety or compliance, in the judgment of the investigator.
• Unstable diabetes with blood glucose > 2 g/L.
• Known hypersensitivity to any active pharmaceutical agent or constituent of the [68Ga]Ga-PentixaFor and/or [18F]FDG product.
• Body weight of less than 48 kg.
• Mental impairment that may compromise the ability to give informed consent and comply with study requirements.
• Pregnant, likely to be pregnant or breastfeeding woman.
• Patient deprived of liberty, under judicial safeguard, under curatorship or placed under the authority of a guardian.
• Disorder preventing understanding of trial information or informed consent.