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).
Single group
Biological NI-1801
DrugTreatment 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. Each subject will receive the assigned dose of NI-1801 on Cycle 1, Day 1. Subsequent doses will be given Q2W, which may be adjusted to every three weeks if recommended from the ongoing PK/PD model analysis.
NI-1801 in combination with anti-PD1 (Pembrolizumab)
DrugIn the combination with pembrolizumab cohort, the starting NI-1801 dose will be 300 mg. Pembrolizumab will be administered at the dosage of 400 mg every 6 weeks, in 4 cycles. Pembrolizumab will be administered as first drug; later, NI-1801 will be infused after 30 minutes.
NI-1801 in combination with paclitaxel
DrugThe 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.
Paclitaxel
DrugThe control arm will be treated with weekly administration of paclitaxel (80 mg/m\^2) over 4-week cycles.
Dose Limiting Toxicity (DLT)
Is defined as any of the toxicities occurring within the DLT window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.
Non-Tolerated Dose (NTD)
Is defined as a dose level at which 2 or more of up to 6 evaluable patients in a cohort experience a DLT in the 4-week DLT window.
Maximum Tolerated Dose (MTD)
Is defined as the last cohort below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during the 4-week DLT window.
Progression Free Survival (PFS) (Randomized Cohort only)
Defined as the time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.
Overall Response Rate (ORR)
Is defined as the proportion of patients who achieve a partial response (PR) or better better, i.e., PR + complete response (CR), of the defined target lesions compared to baseline.
Disease Control Rate (DCR)
Is defined as the proportion of patients who achieve a clinical benefit from NI-1801 treatment, i.e., CR + PR + stable disease (SD).
Best Overall Response (BOR)
Is defined as the best response recorded from start of NI-1801 treatment until the first date that recurrent or progressive disease is objectively documented.
Time to Response
Is defined as the time from the first NI-1801 dose date to the date of first documented response (i.e., PR or better)
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