Recruiting PHASE1 Epithelial Ovarian Cancer

New treatment option for Epithelial Ovarian Cancer

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

ClinicalTrials.gov ID: NCT05403554

What this study is testing

What is Biological NI-1801?

Biological NI-1801 is an investigational medicine, given as an once-weekly, being studied as a potential treatment for epithelial ovarian cancer.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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.

Phase 1: an early, usually small safety study
Time commitment: about 12 months
Which group you join is decided by chance.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join if

Main 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...
MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 40% of tumor cells. Staining for MSLN expression can be performed using archival...
Patients with advanced, metastatic, or recurrent disease

You likely can't join if

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...
Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study...
Severe cardiac dysfunction (NYHA classification III-IV).

See the full eligibility criteria

Who can join

Main 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 people with histologically or...
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...
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 for the assigned by chance 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: 3.1. 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...
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...
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

What rules you out

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...
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...
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...
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...
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...
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...
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...
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 assigned by chance 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.

The study team makes the final eligibility decision.

Where it's taking place

Paris, France
Rennes, France
Villejuif, France, France
Milan, Italy
Verona, Italy

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The study runs about 12 months per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Paris, France; Rennes, France; Villejuif, France, France; Milan, Italy; Verona, Italy. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.