A Phase 1b/2 Study of the Safety and Efficacy of the Monoclonal Antibody OM-RCA-01 in Patients With Metastatic Tumors Expressing Fibroblast Growth Factor Receptor 1

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).

Inclusion criteria

• Signed and dated Informed Consent Form confirming voluntary participation in the study.
• Age ≥ 18 years at the time of consent.
• Body weight ≥ 50 kg.
• Histologically confirmed metastatic solid tumors:

• clear-cell renal cell carcinoma;
• non-small cell lung cancer (adenocarcinoma or squamous cell cancer without EGFR and ALK mutations);
• prostate cancer (castration-resistant adenocarcinoma);
• breast cancer (adenocarcinoma with specified status for estrogen receptors, progesterone receptors, HER2);
• head and neck tumors (squamous carcinoma, salivary gland cancer).
• Immunohistochemical expression of FGFR1 of 2+ or higher.
• Documented disease progression after at least two lines of standard therapy, or lack of available or feasible alternative standard treatment options for any reason.
• Presence of at least one measurable lesion according to RECIST 1.1 criteria.
• Availability of formalin-fixed and paraffin-embedded tumor tissue samples for biomarker analysis.
• ECOG performance status 0 or 1.
• Adequate organ function, confirmed by laboratory test results obtained within 7 days prior to Cycle 1 Day 1, meeting the following parameters:

• Hemoglobin level ≥ 90 g/L
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
• Platelet count ≥ 100 × 10⁹/L
• Serum creatinine level ≤ 1.5 × upper limit of normal (ULN)
• Glomerular Filtration Rate (GFR) ≥ 30 mL/min
• AST and ALT ≤ 3 × ULN (≤ 5 × ULN in patients with liver metastases)
• Serum phosphorus within normal limits (≥ lower limit of normal and ≤ upper limit of normal)
• Serum calcium ≥ lower limit of normal
• Serum potassium ≥ lower limit of normal (note: use of medications to increase potassium during screening is permitted)
• Life expectancy of more than 12 weeks.
• Absence of any psychological, familial, social or geographical circumstances that could potentially serve as an obstacle to the fulfillment of the study protocol and follow-up procedures according to the prescribed schedule and the ability of the study participant to follow the requirements of the protocol; these circumstances should be discussed with the patient before inclusion in the study.
• Women capable of childbearing must be using an effective method of contraception.

Exclusion criteria

• Participation in another clinical trial or concomitant treatment with any investigational drug, or administration of any investigational anticancer therapy within 28 days prior to inclusion in this study.
• Presence of central nervous system (CNS) metastases and/or medullary carcinomatosis at the time of inclusion.

Exception: Patients with CNS metastases who have received therapy may participate if they have been clinically stable for at least 1 month prior to enrollment, defined by:

• No evidence of new or progressive CNS metastases
• No ongoing steroid therapy
• Stable mental status sufficient to provide informed consent
• History of or current evidence of any condition, therapy, or laboratory abnormality that could:

• Limit interpretation of study results,
• Prevent completion of the study protocol, or
• Pose a risk to patient safety or well-being. This includes any serious or unstable general medical, psychiatric, or other conditions potentially jeopardizing safety, informed consent, or compliance.
• Any second malignancy within the previous 5 years, except for adequately treated cervical carcinoma in situ, squamous cell carcinoma of the skin, or basal cell carcinoma of the skin with limited growth, provided these are well controlled.
• Known regular use of illicit substances or recreational drugs, or a history of drug abuse or alcoholism within the past year.
• Plans to conceive during the study period, current pregnancy, or lactation.
• Known HIV-positive status.
• Known active hepatitis B or C infection.
• Evidence of active bleeding or hemorrhagic diathesis.
• Radiation therapy within 14 days prior to inclusion.
• Receipt of any anti-tumor treatments including:

• Surgery or tumor embolization within 14 days prior to the first OM-RCA-01 dose, or
• Chemotherapy, immunotherapy, biological therapy, investigational therapy, or endocrine therapy (except ongoing androgen deprivation therapy for prostate cancer) within 14 days or within two half-lives of the drug (whichever is longer) prior to the first OM-RCA-01 dose.
• Prior treatment with any FGFR-inhibiting or FGFR-blocking agents.