One of the most relevant targets in the field of novel targeted anticancer therapy is the family of receptors to fibroblast growth factor receptors (FGFRs). FGFR1 is the main representative of the FGFR family. The goal of this clinical trial is to learn if monoclonal anti-FGFR1 antibody (OM-RCA-01) works to treat metastatic cancers expressing FGFR1. It will also learn about the safety of drug OM-RCA-01. The main questions it aims to answer are: 1. What medical problems do participants have when receiving drug OM-RCA-01? 2. What dose of the drug should patients receive in the next studies? 3. Does tumor growth slow down in patients receiving OM-RCA-01? All patients in this study will receive the antibody treatment. The drug will be given through a vein (by IV infusion) every two weeks, for as long as the disease remains under control and the treatment is well tolerated.
FGFR1 is expressed on cells of various tumors, enabling their development. Currently, there are no reported monoclonal antibodies that block FGFR1, and only one chemically synthesized non-selective pan-FGFR inhibitor has been approved in the treatment of FGFR1-positive relapsed or refractory myeloid/lymphoid neoplasms. OM-RCA-01 is an original innovative targeting drug focused on blocking FGFR1. OM-RCA-01 binds to the extracellular part of FGFR1. The main mechanism of action is blocking the activation processes of FGFR1. In studies, OM-RCA-01 was found to be a high-affinity and specific to FGFR1 antibody, inhibiting the phosphorylation of the receptor and the subsequent intracellular cascade. The amount of human protein in the structure of the humanized antibody is 92.9%. The present clinical trial is a Phase 1b/2, multicenter, open-label, non-randomized, cohort study designed to evaluate the safety and preliminary efficacy of the monoclonal antibody OM-RCA-01 in patients with metastatic solid tumors expressing FGFR1. This study adopts a basket trial design, enrolling patients based on the shared molecular characteristic of FGFR1 expression regardless of tumor histology. This approach enables the assessment of the anti-FGFR1 antibody's activity across multiple tumor types simultaneously. Patients with FGFR1 expression meeting inclusion criteria (see the relevant section) will be enrolled into one of five tumor-specific cohorts: * Renal cell carcinoma (RCC); * Non-small cell lung cancer (NSCLC); * Head and neck cancer (HNC); * Breast cancer (BC); * Prostate cancer (PCa) A total of 58 patients will be included. The study drug is administered intravenously, every 14 days till disease progression (RECIST 1.1) or unexaptable toxicity (CTCAE v.5.0).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
58
OM-RCA-01, solution for infusion, 25 mg/mL; 50 mg (dose level 1) or 100 mg (dose level 2), intravenously, every 14 days
Republican Dispensary of Tatarstan
Kazan', Russia
ACTIVE_NOT_RECRUITINGA.I. Kryzhanovsky Krasnoyarsk Regional Cancer Center
Krasnoyarsk, Russia
RECRUITINGHadassah Medical
Moscow, Russia
RECRUITINGI.P. Pavlov First Saint Petersburg State Medical University
Saint Petersburg, Russia
RECRUITINGRepublican Clinical Oncology Dispensary
Ufa, Russia
RECRUITINGPrimary endpoint in the phase 1b study
Recommended Phase 2 Dose (RP2D)
Time frame: 6 months
Primary endpoint in the phase 2 study
Objective response rate according to RECIST 1.1 criteria as assessed by the investigator
Time frame: 12 months
Number of Participants with Treatment-Related Adverse Events (AEs) as Assessed by CTCAE v5.0
Time frame: 12 months
Number of Participants with serious AEs
Time frame: 12 months
Median progression-free survival
Time frame: 12 months
12-month progression-free survival rate
Time frame: 12 months
Median overall survival
Time frame: 12 months
12-month overall survival rate
Time frame: 12 months
Median duration of response
Time frame: 12 months
Quality of life, assessed using the EORTC QLQ-C30 questionnaire
in patients before and after 8 weeks of therapy (0-100)
Time frame: 8 weeks
Concentration of anti-drug antibodies
Assessment of immunogenicity
Time frame: 12 months
Pharmacokinetics profile: Cmax
the highest concentration of OM-RCA-01 in the blood
Time frame: 1 month
Pharmacokinetics profile: Tmax
The time it takes for a antibody to reach the maximum concentration
Time frame: 1 month
Pharmacokinetics profile: AUC0-t
the area under the plasma concentration-time curve from time zero to time t
Time frame: 1 month
Pharmacokinetics profile: CL
clearance
Time frame: 1 month
Pharmacokinetics profile: T1/2
the time required for plasma concentration of a OM-RCA-01 to decrease by 50%
Time frame: 1 month
Pharmacokinetics profile: Vss
Steady-state volume of distribution
Time frame: 1 month
Pharmacokinetics profile: Kel
the elimination rate constant
Time frame: 1 month
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