A Study of NI-1801 in Patients With Mesothelin Expressing Solid Cancers

Phase 1

Recruiting

• Conditions: Epithelial Ovarian Cancer; Triple Negative Breast Cancer; Non-squamous Non-small-cell Lung Cancer; Pancreatic Adenocarcinoma (ductal Adenocarcinoma); Endometrioid Ovarian Cancer
• Interventions: Drug: Biological NI-1801; Drug: NI-1801 in combination with anti-PD1 (Pembrolizumab); Drug: NI-1801 in combination with paclitaxel; Drug: Paclitaxel

• Registration Number: NCT05403554
• Lead Sponsor: Light Chain Bioscience - Novimmune SA

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-29
• Study First Submitted: 2022-05-24
• Study First Submitted QC: 2022-05-31
• Study First Posted: 2022-06-03
• Status Verified: 2024-09
• Last Update Submitted: 2024-10-25
• Last Update Posted: 2024-10-29
• Primary Completion: 2026-05-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NI-1801 Single Agent	Biological NI-1801	NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors
NI-1801 in Combination with Pembrolizumab	NI-1801 in combination with anti-PD1 (Pembrolizumab)	NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors in combination with anti-PD-1 antibody
Randomized cohort	NI-1801 in combination with paclitaxel	In the randomized, open-label cohort design, the experimental arm will receive the investigational drug NI-1801 at the P2RD in combination with weekly administration of paclitaxel (80 mg/m\^2) over 4-week cycles.
Randomized cohort	Paclitaxel	In the randomized, open-label cohort design, the experimental arm will receive the investigational drug NI-1801 at the P2RD in combination with weekly administration of paclitaxel (80 mg/m\^2) over 4-week cycles.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT)	Up to 12 months	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)	Up to 12 months	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)	Up to 12 months	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)	Up to 12 months	Defined as the time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.
Adverse Events (AEs)	Up to 12 months	Number of patients with AEs as assessed by CTCAE v5.0

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to 12 months	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)	Up to 12 months	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)	Up to 12 months	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	Up to 12 months	Is defined as the time from the first NI-1801 dose date to the date of first documented response (i.e., PR or better)
Duration of Response	Up to 12 months	Is defined as the time from the earliest date of documented response (i.e., CR or PR) to the first date that disease progression, recurrence of disease, or death, whichever occurs first, is objectively documented
Progression Free Survival	Up to 12 months	Is defined as the time from the first dose of NI-1801 to progressive disease or death from any cause, whichever occurs first
Overall Survival	Up to 12 months	Is defined as the time from the first dose of NI-1801 to death from any cause
Pharmacokinetics - Cmax	Up to 12 months	Maximum concentration of drug
Pharmacokinetics - tmax	Up to 12 months	Time to maximum concentration
Pharmacokinetics - t1/2	Up to 12 months	Terminal Half-life
Pharmacokinetics - AUC	Up to 12 months	Area under the curve
Pharmacokinetics - CL	Up to 12 months	Total body clearance
Presence of anti-drug antibodies (ADA)	Up to 12 months	Detection of ADAs in patients
Frequency of anti-drug antibodies (ADA)	Up to 12 months	Frequency of ADAs in patients
Functional impact of anti-drug antibodies (ADA)	Up to 12 months	ADAs impact on Cmax and AUC as well as response variables
Biomarker CA125 (Randomized cohort only)	Up to 12 months	Evaluate changes of CA125 levels compared to baseline

Trial Locations

Locations (7)

Gustave Roussy; 🇫🇷 Villejuif, France, France

Institut Curie; 🇫🇷 Paris, France

Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France

Centre Eugène Marquis; 🇫🇷 Rennes, France

Humanitas Research Hospital; 🇮🇹 Milano, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Centro Ricerche Cliniche Verona; 🇮🇹 Verona, Italy