Actively Recruiting
A Phase 1, Open-Label, Dose Finding Study of NI-1801, a Bispecific Mesothelin X CD47 Engaging Antibody, As a Single Agent, in Combination with Anti-PD-1 Antibody, and in Combination with Weekly Paclitaxel (Standard of Care) in Patients with Mesothelin Expressing Ovarian, Pancreatic, Non-Small-Cell-Lung and Triple-Negative Breast Cancers
Led by Light Chain Bioscience - Novimmune SA · Updated on 2024-10-29
70
Participants Needed
7
Research Sites
17 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating NI-1801, a bispecific antibody targeting mesothelin and CD47, in patients with advanced, metastatic, or recurrent solid tumors that express mesothelin. This Phase 1, open-label study includes dose escalation and expansion phases to determine the safety, tolerability, and recommended dose of NI-1801, both alone and in combination with an anti-PD-1 antibody. A randomized cohort specifically targets patients with platinum-resistant ovarian cancer to compare NI-1801 plus paclitaxel against standard paclitaxel treatment. Treatments are given in 28-day cycles for up to 12 months or until disease progression, unacceptable side effects, or withdrawal. The study includes multiple groups: NI-1801 alone at escalating doses, NI-1801 combined with pembrolizumab (anti-PD-1 antibody), and a randomized cohort where patients receive either NI-1801 plus weekly paclitaxel or paclitaxel alone. Dosing schedules involve biweekly or adjusted intervals, and pembrolizumab is given every 6 weeks. Participants will undergo biopsies, tumor assessments, and monitoring of side effects and treatment response throughout the study. Researchers will measure dose-limiting toxicities, maximum tolerated dose, progression-free survival, and adverse events over up to 12 months. Additional evaluations include response rates, duration of response, pharmacokinetics, and biomarker analyses. Safety follow-up and adherence to study procedures are maintained during treatment and observation periods.
CONDITIONS
Brief Title
A Study of NI-1801 in Patients with Mesothelin Expressing Solid Cancers
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults 18 years or older at the time of consent
- Confirmed diagnosis of epithelial ovarian cancer (high-grade serous or endometrioid), triple negative breast cancer, non-squamous non-small-cell lung cancer, or pancreatic adenocarcinoma as applicable per study arm
- Mesothelin expression with staining intensity of 2+ or higher in at least 40% of tumor cells confirmed by immunohistochemistry
- Advanced, metastatic, or recurrent disease after at least one prior systemic treatment and not eligible or intolerant to available therapies
- Measurable disease according to RECIST guideline v1.1
- Accessible lesions for biopsies if in single agent or pembrolizumab combination cohorts
- Eastern Cooperative Oncology Group performance status 0-1
- Negative pregnancy test at inclusion
- Life expectancy of at least 2 months
- For randomized arm, female patients with platinum-resistant high-grade serous epithelial ovarian cancer who meet additional treatment history and progression criteria
- Adequate hematologic, liver, and kidney function
- Willing and able to sign informed consent and comply with protocol
You will not qualify if you...
- Known hypersensitivity to NI-1801 or its components
- Radiotherapy to target lesions within 4 weeks before first NI-1801 infusion
- Prior anti-cancer therapy within 2 weeks or up to 4 weeks washout before study treatment
- Participation in other investigational therapies during the study
- Severe cardiac dysfunction (NYHA III-IV) or significant hepatic dysfunction unless due to liver metastasis
- Known HIV infection or history of hepatitis B or C infection; active SARS-CoV-2 infection
- Uncontrolled infections or recent intravenous anti-infective treatment
- Concurrent active malignancy requiring systemic treatment
- Known central nervous system metastases
- Low platelet count (<100 x 10^9/L), anemia (Hb <10 g/dL), or low absolute neutrophil count (<1 x 10^9/L)
- Pregnancy or lactation
- Psychiatric illness or substance abuse that interferes with compliance or consent
- Significant medical conditions increasing study risk, including recent major surgery
- Prior treatment with CD47, SIRPα, or mesothelin-targeting agents
- Unresolved toxic effects from prior therapies exceeding specified grades
- Legal incapacity or guardianship limiting consent
- Additional exclusions for pembrolizumab combination cohort including autoimmune diseases, prior severe immune-related toxicity, and hypersensitivity to pembrolizumab
- Exclusions for randomized arm including specific ovarian cancer histologies, platinum-refractory disease, prior wide-field radiotherapy affecting bone marrow, serious infections, significant cardiac disease, liver cirrhosis, interstitial lung disease, hypersensitivity to monoclonal antibodies, pregnancy or lactation, CNS metastases, recent other malignancies, and prior hypersensitivity to study drugs
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 12 months
Participants receive NI-1801 as a single agent, in combination with anti-PD-1 antibody pembrolizumab, or in combination with weekly paclitaxel chemotherapy as part of 28-day treatment cycles. Treatment continues for up to 12 months until disease progression, unacceptable toxicity, or withdrawal.
Dosing every two weeks and additional visits for pembrolizumab every 6 weeks; weekly visits for paclitaxel during 4-week cycles
Trial Site Locations
Total: 7 locations
1
Institut Curie
Paris, France, 75005
Actively Recruiting
2
Hôpital Européen Georges Pompidou
Paris, France, 75015
Actively Recruiting
3
Centre Eugène Marquis
Rennes, France, 35042
Actively Recruiting
4
Gustave Roussy
Villejuif, France, France, 94800
Actively Recruiting
5
Humanitas Research Hospital
Milan, Italy, 20089
Actively Recruiting
6
Istituto Europeo di Oncologia
Milan, Italy, 20141
Actively Recruiting
7
Centro Ricerche Cliniche Verona
Verona, Italy, 37134
Actively Recruiting
Research Team
C
Clinical Project Manager
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
3
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