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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer; Epithelial Ovarian Cancer; Non-squamous Non-small-cell Lung Cancer
• Intervention / Treatment: Biological: NI-1801

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Project Manager; Phone Number: +41 22 552 72 59; Email: ni1801clinical@lightchainbio.com

Study Locations

• France
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
    • Principal Investigator: E. Romano, MD
  • Paris, France, 75015
    • Recruiting
    • Hopital Europeen Georges Pompidou
    • Principal Investigator: J. Medioni, MD
  • Rennes, France, 35042
    • Recruiting
    • Centre Eugène Marquis
    • Principal Investigator: T. de la Motte Rouge, MD
• Italy
  • Milano, Italy, 20141
    • Recruiting
    • Istituto Europeo di Oncologia
    • Principal Investigator: G. Curigliano, MD
  • Milano, Italy, 20089
    • Recruiting
    • Humanitas Research Hospital
    • Principal Investigator: M. Simonelli, MD
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche Verona
    • Principal Investigator: A. Zivi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NI-1801

Biological: NI-1801; All treatments will be administered in 28-day cycles. Each subject will receive the assigned dose of NI-1801 on Cycle 1, Day 1. Subsequent doses will be given once weekly (QW) in Cycles 1 and 2 (e.g., Days 1, 8, 15, and 22), and once every two weeks (Q2W) in Cycles 3 through 6 (e.g., Days 1 and 15). NI-1801 treatment can extend beyond 6 cycles for those patients who do not have disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of patients with AEs	Up to 12 months
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.	Up to 12 months
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.	Up to 12 months
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.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 12 months
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).	Up to 12 months
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.	Up to 12 months
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)	Up to 12 months
Duration of Response	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	Up to 12 months
Progression Free Survival	Is defined as the time from the first dose of NI-1801 to progressive disease or death from any cause, whichever occurs first	Up to 12 months
Overall Survival	Is defined as the time from the first dose of NI-1801 to death from any cause	Up to 12 months
Pharmacokinetics - Cmax	Maximum concentration of drug	Up to 12 months
Pharmacokinetics - tmax	Time to maximum concentration	Up to 12 months
Pharmacokinetics - t1/2	Terminal Half-life	Up to 12 months
Pharmacokinetics - AUC	Area under the curve	Up to 12 months
Pharmacokinetics - CL	Total body clearance	Up to 12 months
Presence of anti-drug antibodies (ADA)	Detection of ADAs in patients	Up to 12 months
Frequency of anti-drug antibodies (ADA)	Frequency of ADAs in patients	Up to 12 months
Functional impact of anti-drug antibodies (ADA)	ADAs impact on Cmax and AUC as well as response variables	Up to 12 months

Collaborators and Investigators

• Sponsor: Light Chain Bioscience - Novimmune SA
• Investigators: Study Director: Chief Medical Officer, MD, LCB - Novimmune SA

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: May 24, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Ovarian Neoplasms; Breast Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma, Ovarian Epithelial; Triple Negative Breast Neoplasms
• Other Study ID Numbers: LCB-1801-001; 2021-003808-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No