A Phase 1, Open-label, Dose Finding Study of NI-1801, a Bispecific Mesothelin x CD47 Engaging Antibody, in Patients With Mesothelin Expressing Solid Cancers

LCB-1801-001

Study LCB-1801-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of NI-1801 in subjects with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of NI-1801, administered intravenously (IV) to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of both the first dose and subsequent doses of NI-1801. The expansion part (Part B) will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 20 subjects in order to determine the recommended Phase 2 dose (RP2D). Treatments will be administered in 28-day cycles for up to 6 months until confirmed disease progression, unacceptable toxicity, or subject/Investigator decision to withdraw. NI-1801 treatment can extend beyond 6 cycles for those patients who do not have disease progression.

2022-04-29

2025-06-30

2025-09-30

Recruiting

Early phase I

40

Main Inclusion Criteria: 1. Adults ≥ 18 years of age at the time of signing the informed consent form. 2. Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer (high-grade serous or endometroid), triple-negative breast cancer, or non-squamous non-small cell lung cancer. 3. MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 60 % of tumor cells. 4. Patients with advanced, metastatic, or recurrent disease * after at least 1 prior systemic treatment for the primary malignancy and * who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer a clinical benefit to patients with these tumor entities. 5. Measurable disease according to the revised RECIST guideline version 1.1 6. Eastern Cooperative Oncology Group performance status 0-1. 7. Adequate organ function 8. Adequate contraception 9. Life expectancy of at least 2 months. Main Exclusion Criteria: 1. Patient has known hypersensitivity to NI-1801 or any of the constituent compounds. 2. Radiotherapy to the target lesions within 4 weeks prior to the first NI-1801 infusion. 3. Prior anti-cancer therapy including chemotherapy, hormonal therapy, and investigational agents within 2 weeks or within ≤ 5 half-lives prior to starting NI-1801 dosing (up to a maximum of 4 weeks), whichever is longer. 4. Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study. 5. Severe cardiac dysfunction (NYHA classification III-IV). 6. Significant hepatic dysfunction (serum bilirubin ≥ 1.5 mg/dL or AST and/or ALT ≥ 2.5 times normal level), unless related to liver metastasis. 7. Uncontrolled active systemic bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks prior to first dose of NI-1801. 8. Patients with concomitant active malignancy, requiring ongoing systemic treatment. 9. Patients with known CNS metastases. 10. Platelet count \< 100 x 10\^9/L (transfusion support within 14 days before the test is not allowed). 11. Hemoglobin \< 10.0 g/dL. Prior RBC transfusion is permitted. 12. ANC \< 1 x 10\^9/L (the use of colony stimulating factors, G-CSF or GM-CSF, within 14 days before the test is not allowed). 13. Pregnancy and lactation. 14. Significant medical diseases or conditions, including laboratory abnormalities, as assessed by the Investigators and Sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, and severely immunocompromised state, major surgery ≤ 4 weeks prior to starting NI-1801. 15. Prior treatment with a CD47, SIRPα, or MSLN targeting agent. 16. Patients in whom acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure have not resolved to Grade ≤ 1 or returned to baseline except for alopecia (any grade), anemia, and peripheral neuropathy (for the latter, recovery to Grade ≤ 2 is acceptable).

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2023-05-30