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

NCT05403554 | Recruiting Phase 1

• 2 other identifiers: LCB-1801-0012021-003808-40
• Study Type: interventional
• Target: 70
• Locations: 2 countries
• Sites: 7

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 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.

Conditions

Epithelial Ovarian Cancer; Triple Negative Breast Cancer; Non-squamous Non-small-cell Lung Cancer; Pancreatic Adenocarcinoma (ductal Adenocarcinoma); Endometrioid Ovarian Cancer

Outcome Measures

Primary Outcomes (5)

• 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

• 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.

  Up to 12 months

• Adverse Events (AEs)

  Number of patients with AEs as assessed by CTCAE v5.0

  Up to 12 months

Secondary Outcomes (16)

• Overall Response Rate (ORR)

  Up to 12 months

• Disease Control Rate (DCR)

  Up to 12 months

• Best Overall Response (BOR)

  Up to 12 months

• Time to Response

  Up to 12 months

• Duration of Response

  Up to 12 months

Study Arms (3)

NI-1801 Single Agent

EXPERIMENTAL

NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors

Drug: Biological NI-1801

NI-1801 in Combination with Pembrolizumab

EXPERIMENTAL

NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors in combination with anti-PD-1 antibody

Drug: NI-1801 in combination with anti-PD1 (Pembrolizumab)

Randomized cohort

ACTIVE COMPARATOR

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.

Drug: NI-1801 in combination with paclitaxel; Drug: Paclitaxel

Interventions

Biological NI-1801 DRUG

Treatment 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 Single Agent

NI-1801 in combination with anti-PD1 (Pembrolizumab) DRUG

In 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 Pembrolizumab

NI-1801 in combination with paclitaxel DRUG

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.

Randomized cohort

Paclitaxel DRUG

The control arm will be treated with weekly administration of paclitaxel (80 mg/m\^2) over 4-week cycles.

Randomized cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• Measurable disease according to the revised RECIST guideline version 1.1(3)
• Patients treated in either the single agent recommended dose expansion cohort or in the combination with pembrolizumab cohort should have accessible lesions at screening for baseline and on treatment biopsies.
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
• Life expectancy of at least 2 months.
• Female patients ≥ 18 years of age.
• Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer.
• Patients must have platinum-resistant disease:
• Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between greater than 3 months and ≤ 6 months after the date of the last dose of platinum.
• Patients who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum

You may not qualify if:

• 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.
• Severe cardiac dysfunction (NYHA classification III-IV).
• Significant hepatic dysfunction (serum bilirubin ≥ 1.5 mg/dL or AST and/or ALT ≥ 2.5 times normal level), unless related to liver metastasis.
• Patients with known human immunodeficiency virus (HIV) infection or known history or serological evidence of prior hepatitis B or C virus infection. Active SARS-COV2 infection.
• 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.
• Patients with concomitant active malignancy, requiring ongoing systemic treatment.
• Patients with known CNS metastases.
• Platelet count lower than 100 x 10\^9/L (transfusion support within 14 days before the test is not allowed).
• Hemoglobin lower than 10.0 g/dL. Prior RBC transfusion is permitted.
• ANC lower than 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).
• Pregnancy and lactation.
• History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements or give informed consent.
• Significant medical diseases or conditions, including laboratory abnormalities, as assessed by the Investigators and Sponsor, which 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.
• Prior treatment with a CD47, SIRPα, or MSLN targeting agent.

Sponsors & Collaborators

• Light Chain Bioscience - Novimmune SA: lead

Study Sites (7)

Institut Curie

Paris, 75005, France

RECRUITING

Hôpital Européen Georges Pompidou

Paris, 75015, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

RECRUITING

Gustave Roussy

Villejuif, France, 94800, France

RECRUITING

Humanitas Research Hospital

Milan, 20089, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Centro Ricerche Cliniche Verona

Verona, 37134, Italy

RECRUITING

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial; Triple Negative Breast Neoplasms

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Chief Medical Officer, MD

  LCB - Novimmune SA

  STUDY DIRECTOR

Central Study Contacts

Clinical Project Manager

CONTACT

+41 79 26 83 513; ni1801clinical@lightchainbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: June 3, 2022
• Study Start: April 29, 2022
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: October 29, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4); IT (3)