This is a prospective, single-center, open-label investigator-initiated study designed to evaluate the safety, tolerability, radiation dosimetry, biodistribution, and preliminary antitumor activity of \[177Lu\]Lu-RTX-2358 in combination with immune checkpoint inhibitors (ICIs) in patients with fibroblast activation protein (FAP)-positive metastatic non-small cell lung cancer (NSCLC). Eligible participants will receive one or two cycles of \[177Lu\]Lu-RTX-2358 followed by standard PD-1 inhibitor therapy. Safety, tumor response, biodistribution, radiation dosimetry, and survival outcomes will be evaluated throughout treatment and follow-up.
Written informed consent must be obtained prior to any study-related procedures.
Age ≥ 18 years old.
Histologically or cytologically confirmed metastatic non-small cell lung cancer (NSCLC).
FAP-positive lesions confirmed by FAPI PET imaging.
History of another active malignancy requiring treatment within 2 years before the first administration of [177Lu]Lu-RTX-2358, except adequately treated basal cell carcinoma of the skin or carcinoma in situ treated with curative intent.
Symptomatic brain metastases or central nervous system metastases requiring active treatment. Participants with previously treated brain metastases are eligible if the disease has remained clinically and radiographically stable for at least 24 weeks.
Symptomatic spinal cord compression or radiographic evidence of impending spinal cord compression.
Major surgery, open biopsy (excluding needle biopsy), or significant traumatic injury within 4 weeks before the first administration of [177Lu]Lu-RTX-2358.
Single group
[177Lu]Lu-RTX-2358
Drug\[177Lu\]Lu-RTX-2358 is a lutetium-177-labeled fibroblast activation protein (FAP)-targeted radioligand administered by intravenous infusion. Participants will receive one or two treatment cycles of approximately 7.4 GBq (200 mCi) per administration, depending on cohort assignment. A dosimetry cohort may receive a single low-dose administration (approximately 0.74 GBq, one-tenth of the therapeutic dose) followed by serial SPECT/CT imaging to evaluate biodistribution and radiation dosimetry before therapeutic administration.A commercially approved programmed cell death protein 1 (PD-1) inhibitor will be administered according to the approved prescribing information and institutional standard of care. Treatment will begin approximately 14 days after the first administration of \[177Lu\]Lu-RTX-2358 and will continue every 3 weeks until disease progression, unacceptable toxicity, or treatment discontinuation. The selected PD-1 inhibitor will remain unchanged throughout the combination treatmen
Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
To evaluate the safety and tolerability of \[177Lu\]Lu-RTX-2358 in combination with a PD-1 inhibitor by assessing the incidence, severity, seriousness, and relationship of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs), graded according to NCI CTCAE version 5.0.
Objective Response Rate (ORR)
Objective response rate, defined as the proportion of participants achieving a confirmed complete response (CR) or partial response (PR) according to RECIST version 1.1.
Disease Control Rate (DCR)
Disease control rate, defined as the proportion of participants achieving complete response (CR), partial response (PR), or stable disease (SD) according to RECIST version 1.1.
Click on the lead sponsor to view all of their trials.
