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

NCT07689643 | Recruiting Early Phase 1

• 1 other identifier: Xlan-20251245
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Non-small Cell Lung Cancer

Keywords

Metastatic Non-Small Cell Lung Cancer; 177Lu; FAP; Radioligand Therapy; PD-1

Outcome Measures

Primary Outcomes (1)

• 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.

  From the first administration of [177Lu]Lu-RTX-2358 until 30 days after the last administration of study treatment.

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  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)

  Up to 12 months after the last study treatment.

Study Arms (1)

[177Lu]Lu-RTX-2358 plus Immune Checkpoint Inhibitor

EXPERIMENTAL

Participants will receive one or two intravenous administrations of \[177Lu\]Lu-RTX-2358 in combination with standard PD-1 inhibitor therapy. The treatment schedule depends on cohort assignment.

Drug: [177Lu]Lu-RTX-2358

Interventions

[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

Also known as: PD-1 inhibitor

[177Lu]Lu-RTX-2358 plus Immune Checkpoint Inhibitor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Xiaoli Lan

CONTACT

0086-027-83692633; lxl730724@hotmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 8, 2026
• Study Start: April 28, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: July 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)