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 patients with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN).
The dose escalation part (Part A) of the main study will evaluate the safety and tolerability of escalating doses of NI-1801 to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of NI-1801. The expansion part (Part B) of the main study will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 10 additional subjects in order to determine the recommended Phase 2 dose (RP2D).
Treatments will be administered in 28-day cycles for up to 12 months until disease progression, unacceptable toxicity, or Investigator/patient decision to withdraw study consent.
The dose escalation part (Part A) of the sub-study will evaluate the safety and tolerability of escalating doses of NI-1801 in combination with anti-PD-1 antibody. The expansion part (Part B) of the sub-study will further evaluate the safety and efficacy of NI-1801 administered in combination with anti-PD-1 antibody at or below the MTD.
In the randomized cohort, the experimental arm will receive the investigational drug NI-1801 at the P2RD every two weeks in combination with weekly administration of paclitaxel (80 mg/m\^2) over 4-week cycles. The control arm will be treated with weekly paclitaxel at the same regimen representing one of the standards of care (SoC) in this population. This trial specifically targets patients with platinum-resistant ovarian cancer. This cohort will be made up of 20 evaluable patients, 10 per arm.
Adults ≥ 18 years of age at the time of signing the informed consent form
Histologically or cytologically confirmed diagnosis of epithelial OC (high-grade serous or endometroid), TNBC, or non-squamous NSCLC. For the combination with pembrolizumab, only subjects with histologically or cytologically confirmed diagnosis of epithelial OC (high-grade serous or endometroid), non-squamous NSCLC and ductal pancreatic adenocarcinoma.
MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 40% of tumor cells. Staining for MSLN expression can be performed using archival tumor tissue and is foreseen to be performed at the institution's pathology. A slice for centralized IHC assessment for validation and biomarker analysis is mandatory.
Patients with advanced, metastatic, or recurrent disease
Patient has known hypersensitivity to NI-1801 or any of the constituent compounds.
Radiotherapy to the target lesions within 4 weeks prior to the first NI-1801 infusion.
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. The maximum required washout period will thus not exceed 4 weeks prior to the day of first treatment with NI-1801. Note: Low dose steroids (oral prednisone or equivalent ≤ 20 mg per day, including systemic or topic use), localized noncentral nervous system (CNS) radiotherapy of non-target lesions, and treatment with bisphosphonates and RANKL inhibitors are not criteria for exclusion.
Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study. COVID-19 vaccination is allowed only starting from Cycle 2 (if not completed before study inclusion).