Safety and Preliminary Efficacy of [177Lu]Lu-RTX-2358 Combined With Immune Checkpoint Inhibitors in Patients With FAP-positive Metastatic Non-Small Cell Lung Cancer

Official title

A Single-Center, Prospective, Open-Label, Investigator-Initiated Study Evaluating the Safety, Biodistribution, Radiation Dosimetry, and Preliminary Efficacy of [177Lu]Lu-RTX-2358 Combined With Immune Checkpoint Inhibitors in Patients With FAP-positive Metastatic Non-Small Cell Lung Cancer

Overview

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.

Interventions

• Drug [177Lu]Lu-RTX-2358
  \[177Lu\]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 befor

Primary outcome measures

• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From the first administration of [177Lu]Lu-RTX-2358 until 30 days after the last administration of study treatment.]

Secondary outcome measures (2)

• Objective Response Rate (ORR) [Time frame: From baseline until disease progression, initiation of new anticancer therapy, death, or up to 12 months after the last study treatment, whichever occurs first.]
• Disease Control Rate (DCR) [Time frame: Up to 12 months after the last study treatment.]

Eligibility criteria

Inclusion criteria

• 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.
• At least one measurable lesion per RECIST version 1.1 criteria.
• ECOG performance status 0 or 1.
• Estimated life expectancy ≥ 3 months.
• Adequate bone marrow, hepatic, renal, and coagulation function.
• Willing to comply with all radiation protection requirements throughout study participation.
• Willing to use highly effective contraception during study treatment and post-treatment follow-up period.

Exclusion criteria

• 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.

Prior treatment with any radioligand therapy or therapeutic radiopharmaceutical.

• Receipt of systemic anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, biologic therapy, investigational agents, or antitumor traditional Chinese medicine, within 21 days before the first administration of \[177Lu\]Lu-RTX-2358, unless the protocol-defined washout period has been satisfied.
• Receipt of curative radiotherapy within 6 weeks before the first administration of \[177Lu\]Lu-RTX-2358. Palliative radiotherapy is permitted if completed at least 2 weeks before treatment, involves less than 10% of bone marrow, and does not include target lesions.
• Unresolved toxicities from previous anticancer therapy greater than Grade 1 according to NCI CTCAE version 5.0, except stable chronic toxicities judged by the investigator not to pose a safety risk (e.g., alopecia, peripheral neuropathy, or fatigue).
• Endocrine dysfunction involving the thyroid, adrenal, pituitary, or pancreas that would preclude treatment with immune checkpoint inhibitors.

Known interstitial lung disease, immune-related pneumonitis, pulmonary fibrosis, or active pulmonary fibrosis.

• Severe urinary incontinence, hydronephrosis, bladder outlet obstruction, or other clinically significant urinary tract disorders that may interfere with radiopharmaceutical clearance.
• Clinically significant cardiovascular disease, including myocarditis, pericarditis, myocardial infarction, unstable angina, New York Heart Association Class III or IV heart failure, uncontrolled arrhythmias, uncontrolled hypertension, or conditions associated with clinically significant QT interval prolongation within 6 months before enrollment.
• Active uncontrolled infection, including human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C infection, active syphilis, or any infection requiring systemic therapy that is not adequately controlled.

Serious or non-healing wounds, active ulcers, or fractures requiring ongoing treatment.

• Severe psychiatric illness or any medical condition that, in the investigator's judgment, would compromise participant safety, interfere with study participation, or affect protocol compliance.
• Pregnant or breastfeeding women.
• Known hypersensitivity to \[177Lu\]Lu-RTX-2358 or any of its components. History of significant occupational exposure to ionizing radiation exceeding applicable regulatory limits.
• Participation in another interventional clinical trial within 4 weeks before screening.
• Inability or unwillingness to undergo required study procedures, including PET/CT, SPECT/CT, CT/MRI examinations, or inability to comply with protocol requirements.
• Any other condition that, in the investigator's judgment, would make the participant unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Union Hospital, Huazhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT07689643 · Xlan-20251245

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗