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Status:

RECRUITING

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

Lead Sponsor:

Light Chain Bioscience - Novimmune SA

Conditions:

Epithelial Ovarian Cancer

Triple Negative Breast Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE1

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 malign...

Eligibility Criteria

Inclusion

  • Main Inclusion Criteria for the Single Agent Dose Escalation and the Combination with Pembrolizumab:
  • 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.
  • Negative pregnancy test at inclusion.
  • Life expectancy of at least 2 months.
  • Main Inclusion Criteria for the Randomized study arm:
  • 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:
  • 1. 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.
  • 2. 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
  • Patients must have progressed radiographically on or after their most recent line of therapy.
  • Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low risk, medically routine procedure for IHC confirmation of MSLN expression.
  • 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 can be done at the institution's pathology. A slice for centralized IHC assessment for validation and biomarker analysis is mandatory.
  • Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator).
  • Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment:
  • Adjuvant ± neoadjuvant considered one line of therapy
  • Maintenance therapy (e.g., bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (i.e., not counted independently)
  • Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (i.e., not counted independently)
  • Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
  • ECOG PS of 0 or 1
  • Time from prior therapy:
  • Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
  • Focal radiation completed at least 2 weeks prior to first dose of study drug
  • Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities.
  • Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery.
  • Patients must have adequate hematologic, liver and kidney functions
  • Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
  • Negative pregnancy test at inclusion
  • Main Exclusion Criteria for the Single Agent Dose Escalation and the Combination with Pembrolizumab:
  • 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).
  • 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.
  • 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).
  • People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship/curatorship), people who are unable to express their consent, and people who are subject to a legal guardianship order.
  • Furthermore, subjects presenting with any of the following criteria will not be included in the sub-study (combination with pembrolizumab cohort):
  • History of/active non-infectious pneumonitis or interstitial lung disease.
  • Known hypersensitivity to pembrolizumab or excipients.
  • Participants with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Prior organ or tissue allograft.
  • History of Grade ≥ 3 toxicity related to prior T-cell agonist or checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures.
  • History of myocarditis, regardless of etiology.
  • Main Exclusion Criteria for the Randomized study arm:
  • Patients with clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histology, or low-grade or borderline ovarian tumor.
  • Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy.
  • Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow.
  • Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
  • Active hepatitis B or C infection (whether or not on active antiviral therapy)
  • HIV infection
  • Active cytomegalovirus infection
  • Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated
  • Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
  • Patients with clinically significant cardiac disease including, but not limited to, any one of the following:
  • Myocardial infarction ≤ 6 months prior to first dose
  • Unstable angina pectoris
  • Uncontrolled congestive heart failure (New York Heart Association greater than class II)
  • Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
  • Uncontrolled cardiac arrhythmias
  • Patients assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
  • History of hemorrhagic or ischemic stroke within six months prior to randomization
  • History of cirrhotic liver disease (Child-Pugh Class B or C)
  • Previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
  • Patients with prior hypersensitivity to monoclonal antibodies.
  • Women who are pregnant or lactating.
  • Patients with prior treatment with a CD47, signal regulatory protein (SIRP) alpha, or MSLN targeting agent.
  • Patients with central nervous system (CNS) metastases.
  • Patients with a history of other malignancy within 3 years prior to randomization.
  • Prior known hypersensitivity reactions to study drugs and/or any of their excipients.

Exclusion

    Key Trial Info

    Start Date :

    April 29 2022

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ESTIMATED

    End Date :

    September 30 2026

    Estimated Enrollment :

    70 Patients enrolled

    Trial Details

    Trial ID

    NCT05403554

    Start Date

    April 29 2022

    End Date

    September 30 2026

    Last Update

    October 29 2024

    Active Locations (7)

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    Page 1 of 2 (7 locations)

    1

    Institut Curie

    Paris, France, 75005

    2

    Hôpital Européen Georges Pompidou

    Paris, France, 75015

    3

    Centre Eugène Marquis

    Rennes, France, 35042

    4

    Gustave Roussy

    Villejuif, France, France, 94800