Phase I Clinical Study of LNF2105 in Patients With Advanced Solid Tumors

Official title

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Antitumor Efficacy of LNF2105 in Patients With Advanced Solid Tumors.

Overview

This study is a Phase I clinical trial evaluating the safety, tolerability, pharmacokinetic characteristics, and preliminary antitumor efficacy of LNF2105 in patients with advanced solid tumors.

Interventions

• Drug LNF2105(Antibody-Drug Conjugate (ADC) targeting Nectin-4)
  The dosage of LNF2105 was increased sequentially from 0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg, 2.0 mg/kg, 3.0 mg/kg, to 4.5 mg/kg.

Primary outcome measures

• To evaluate of Safety and Tolerability of LNF2105 in Patients with Advanced Solid Tumors [Time frame: Approximately 24months]
• To confirm Dose Limiting Toxicities (DLT) and determine MTD and RP2D for LNF2105 [Time frame: 28 days]

Secondary outcome measures (11)

• Maximum observed plasma concentration of LNF2105 (ADC), Total Antibody and Free Payload (Cmax) [Time frame: Approximately 24 months]
• Time to reach Cmax of LNF2105 (ADC), Total Antibody and Free Payload (Tmax) [Time frame: 24 month]
• Total Area Under the plasma concentration-time curve of LNF2105 (ADC), Total Antibody and Free Payload (AUC) [Time frame: 24 month]
• Minimum Plasma Concentration (Cmin) of LNF2105 (ADC), Total Antibody and Free Payload [Time frame: 24 month]
• To evaluate the preliminary antitumor activity of LNF2105: Overall response rate (ORR) [Time frame: Approximately 24months]
• To evaluate the preliminary antitumor activity of LNF2105: Progression free survival (PFS) [Time frame: Approximately 24months]
• To evaluate the preliminary antitumor activity of LNF2105: Duration of response (DOR) [Time frame: Approximately 24months]
• To evaluate the preliminary antitumor activity of LNF2105: Disease control rate (DCR) [Time frame: Approximately 24months]
• To evaluate the preliminary antitumor activity of LNF2105: Time to response (TTR) [Time frame: Approximately 24months]
• To evaluate the preliminary antitumor activity of LNF2105: Overall survival (OS) [Time frame: Approximately 24months]
• To evaluate the immunogenicity of LNF2105 [Time frame: Approximately 24months]

Eligibility criteria

Inclusion criteria

• Male or female aged ≥18 years.
• Patients with advanced solid tumors (including but not limited to urothelial carcinoma, breast cancer, non-small cell lung cancer, ovarian cancer, endometrial cancer, and cervical cancer) that have been histologically or cytologically confirmed as having failed/cannot tolerate/have no standard treatment/are currently unsuitable for standard treatment.
• Able to provide previous Nectin-4 expression testing results or preserved/fresh tumor tissue for Nectin-4 expression testing.
• At least one measurable lesion (CT or MRI long axis ≥ 10 mm, lymph node short axis ≥ 15 mm) according to RECIST v1.1 criteria. For lesions previously treated with radiotherapy, they will only be included as measurable lesions if there has been clear disease progression after radiotherapy.
• The function of vital organs must meet the following requirements (no blood components or cytokines may be used within 14 days prior to the first dose).

7\) ECOG score 0-1. 8) Expected survival ≥ 3 months. 9) Willing to participate and sign informed consent form, and willing to follow the trial treatment protocol and visitation plan.

Exclusion criteria

• Prior treatment with an antibody-drug conjugate (ADC) exhibiting one of the following characteristics: payload as a topoisomerase I inhibitor (TOP 1 inhibitor); antibody target as Nectin-4.
• Received any P-glycoprotein (P-gp) inducer/inhibitor, strong CYP3A inhibitor, or breast cancer resistance protein (BCRP) inhibitor within 14 days prior to first administration (see Appendix 3 for the exclusion list).
• Patients who received chemotherapy within 3 weeks or radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor treatments within 4 weeks prior to first administration of the study drug, excluding the following.
• Patients who received systemic glucocorticoid therapy or any other form of immunosuppressive therapy (equivalent to a prednisone dose >10 mg/day) within 2 weeks prior to the first dose.
• Patients whose adverse reactions to previous antitumor therapy have not recovered to a CTCAE 5.0 grade ≤1 or the level specified in the inclusion/exclusion criteria (excluding toxicities deemed safe by the investigator, such as alopecia, grade 2 peripheral neurotoxicity, and stable hypothyroidism after hormone replacement therapy).
• Patients with primary central nervous system (CNS) malignancies, CNS metastases that have failed local treatment, or carcinomatous meningitis; patients with asymptomatic brain metastases, or stable clinical symptoms such as neurological symptoms and who do not require corticosteroids or other treatments targeting brain metastases for ≥4 weeks may be enrolled.
• Patients with uncontrollable pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
• Patients with known interstitial lung disease (ILD) or non-infectious pneumonia, currently symptomatic or requiring prior systemic glucocorticoid therapy, whose toxicity assessment or management is deemed by the investigator to potentially affect the investigational treatment.
• Patients with a history of organ transplantation or allogeneic bone marrow transplantation, or who received autologous stem cell transplantation within 3 months prior to the first dose.
• Patients who underwent major surgery within 4 weeks prior to the first dose or have not yet recovered from surgery.
• Patients with any of the following laboratory findings.
• Patients with uncontrolled or severe cardiovascular disease, including those who developed NYHA Class II or higher congestive heart failure, unstable angina, myocardial infarction, or other cardiovascular diseases within 6 months prior to the first dose; or those with uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg after treatment).
• Patients with active infections requiring intravenous anti-infective therapy or a history of the following conditions, including but not limited to active autoimmune diseases, severe mental illness, severe endocrine disorders such as severe thyroid dysfunction.
• Patients with the following ocular diseases: a) active infection or corneal ulcer; b) history of corneal transplantation; c) expected contact lens wear during the study period; d) poorly controlled glaucoma; e) poorly controlled or progressive retinopathy, wet macular degeneration, uveitis, papilledema, or optic disc disease; f) or other currently existing ocular diseases that would affect the assessment of ocular toxicity after the trial intervention.
• Glycated hemoglobin (HbA1c) ≥ 8.0%.
• Suffering from severe and/or uncontrolled comorbidities, such as decompensated cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, active inflammatory bowel disease, gastrointestinal perforation, intestinal obstruction, or gastrointestinal bleeding.
• Having a bleeding tendency (e.g., abnormal coagulation function tests, clinically significant as determined by the investigator, or clinically significant bleeding symptoms as assessed by the investigator).
• Having received any other clinical trial drug/device treatment within 4 weeks prior to the first dose.
• Having a history of drug abuse or alcoholism within 6 months prior to the first dose.
• Having a history of severe allergies, or a known history of allergy to macromolecular protein preparations/monoclonal antibodies, or to any component of the investigational drug.
• Having received a live or attenuated live vaccine within 4 weeks prior to the first dose.
• Pregnant or breastfeeding women, female participants of childbearing age, or male participants whose partners are women of childbearing age who do not agree to use medically approved effective contraception (such as an intrauterine device or condom) during the study period and for 6 months after the last study drug treatment.
• Individuals deemed unsuitable for enrollment by the investigator.

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07661797 · NTP-LNF2105-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗