BCD-106-1 – An Open-Label Phase 1–2 Cohort Study to Select a Dose and Evaluate the Tolerability, Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BCD-106 in the Treatment of Adult Subjects with Certain Solid Tumors.
During the clinical study BCD-106-1, the tolerability, safety, pharmacokinetics, and pharmacodynamics of BCD-106 will be evaluated, and a preliminary evaluation of its efficacy will be performed in patients with certain solid tumors1, who:
For the first stage2 of the CS:
Have reached the age of 18–75 years at the time of signing the Informed Consent Form.
Have a documented locally progressive unresectable or metastatic malignancy in one of the following sites:
breast cancer (triple-negative phenotype3),
squamous cell carcinoma of the head and neck,
gastric or gastroesophageal junction cancer,
renal cell carcinoma,
non-small cell lung cancer (with activating EGFR mutations)4,
cutaneous melanoma (excluding mucosal melanoma).
Standard treatment methods have been exhausted; at least one line of systemic therapy for locally progressive unresectable or metastatic melanoma has been used (mandatory condition).
Do not have treatment options that can potentially cure the disease.
The clinical trial protocol provides for mandatory testing of tumor samples for the presence of certain biomarkers.
Have at least one measurable tumor lesion according to the RECIST 1.1 criteria.13
Have an ECOG score14) of14 0–1.
Have adequate function of internal organs according to the results of complete blood count, blood chemistry, and coagulation tests.
If they have preserved childbearing potential, they agree to use reliable methods of contraception throughout the study from the moment of signing the Informed Consent Form and for at least 6 months after the last dose of the investigational product BCD-106.
Contraindications for participation in this study include pregnancy, breastfeeding, or planned pregnancy for the entire duration of participation in the study and 6 months after the last administration of the investigaonal product.
For the second5 stage of the CS:
Have reached the age of 18–75 years at the time of signing the Informed Consent Form.
Have documented locally advanced unresectable or metastatic triple-negative breast cancer (TNBC). Subjects with tumor expression of PD-L16 (CPS7 ≥1) will be included in the study.
Do not have BRCA gene mutations8 (if BRCA test results are available).
Have not received systemic therapy for locally recurrent unresectable or metastatic TNBC (in some cases, previous preoperative and postoperative anticancer therapy will be allowed).
Have adequate function of internal organs according to the results of complete blood count, blood chemistry, and coagulation tests.
If they have preserved childbearing potential, they agree to use reliable methods of contraception throughout the study from the moment of signing the Informed Consent Form and for at least 6 months after the last dose of the investigational product BCD-106/chemotherapy (whichever occurs later).
The clinical trial protocol provides for mandatory testing of tumor samples for the presence of certain biomarkers.
Have at least one measurable tumor lesion according to the RECIST 1.1 criteria. An ECOG score of 0–1.
This study has exclusion criteria (precluding participation in this clinical study), which will all be explained to the potential participant by the study doctor. In particular, the exclusion criteria are:
Prior therapy with anti-CD479, monoclonal antibodies, anti-SIRPα10, antibodies or CD47/SIRPα recombinant protein.
Prior antineoplastic therapy (including chemotherapy, targeted therapy, hormonal therapy, or chemoembolization) completed at least 4 weeks before the first dose of the investigational product. Prior radiotherapy completed at least 3 weeks before the first dose of the investigational product (this criterion applies only to the first stage of the study).
Prior anticancer immunotherapy (e.g., pembrolizumab, nivolumab, prolgolimab, atezolizumab, avelumab, durvalumab) is prohibited only for the second stage of the study. For the first stage of the study, prior immunotherapy will be allowed if the subject has no history of severe immune-mediated adverse reactions (imARs) and mild to moderate imARs resolve to baseline before initiation of therapy with the investigational product.
Subjects participating in another interventional study. Simultaneous participation in this study and in an observational (non-interventional) study is allowed.
Subjects receiving anticoagulant therapy (other than anticoagulants for primary prevention of thromboembolic complications).
Subjects who received blood transfusion15 within 2 weeks before signing the Informed Consent Form, or received therapy with erythropoietins, granulocyte/granulocyte-macrophage colony-stimulating factors (G-CSF/GM-CSF), thrombopoietin receptor agonists, or interleukin-11 (oprelvekin) within a month before signing the Informed Consent Form.
The subject received the study11 therapy within 4 weeks prior to the first dose of the investigational product BCD-106.
Subjects taking immunosuppressants within 7 days before the first dose of the investigational product (except for topical drugs, intranasal, or inhaled forms of glucocorticoids, or systemic glucocorticoids at a dose equivalent to ≤10 mg of prednisolone a day).
Any clinically significant ongoing adverse event associated with prior anticancer therapy, with the exception of alopecia and fatigue.
Subjects with active metastases to the central nervous system.
Subjects with an underlying active autoimmune disease or a history of documented autoimmune disease for which systemic therapy has been used within the past 2 years (excluding vitiligo, psoriasis, alopecia, Graves’ disease, for which no systemic treatment has been required in the past 2 years; hypothyroidism, for which only hormone replacement therapy was used, or type 1 diabetes mellitus, for which insulin therapy was used).
A concomitant cancer, except cancers that have been treated radically and in remission for more than 5 years before the start of therapy within the framework of this study. The exception is radically resected cervical carcinoma in situ12 or radically resected basal cell/squamous cell carcinoma.
A clinically significant immunodeficiency.
An active infectious disease requiring systemic etiological therapy within 2 weeks before the first administration of the investigational product.
Active tuberculosis.
Interstitial lung disease (active or past).
A history of non-infectious pneumonitis for which GC therapy was required, or active moderate to severe pneumonitis.
Clinically significant heart failure or a history of acute myocardial infarction less than 6 months before signing the Informed Consent Form.
Active hepatitis B, active hepatitis C, HIV infection.
A history of allogeneic organ or hematopoietic stem cell transplantation.
An allergic reaction to any component of the investigational product. For the second stage, additionally: allergies to accompanying chemotherapy drugs/drugs used for premedication.
Allergic reaction to contrast agents for CT and MRI (both methods).
Pregnancy and lactation.
Conditions that, in the opinion of the Investigator, limit the subject’s ability to fulfill the Protocol requirements (dementia, neurological or mental disorders, drug and alcohol addiction, etc.).
The BCD-106-1 study is being conducted in study centers in different cities of the Russian Federation, such as Moscow, St. Petersburg, Volgograd, Chelyabinsk, and Omsk.
You can ask questions about participation in the clinical study and clarify the contact information of study centers through the “Any questions?” form at the website ct.biocad.ru.
The study doctor will tell the potential participant about other eligibility criteria and contraindications for participation in this clinical study. The potential participant should read the full information about the study and consult the study doctor and/or attending physician.
Clinical Study Authorization No. 668 of the Ministry of Health of the Russian Federation dated November 23, 2022 and the list of approved study centers have been published in the State Register of Medicines.
The term “solid” tumors is used for tumors that have a clear localization, shape, and boundaries, in contrast to tumors originating from cells of the hematopoietic system.
Phase 1 of the study involves patients with locally progressive unresectable or metastatic malignant tumors of various sites, who have exhausted the possibilities of standard therapy, and who will receive different doses of the investigational product BCD-106.
Triple-negative phenotype breast cancer is a special type of malignant breast tumor with no expression of hormonal receptors and the HER2/neu oncoprotein in the tumor.
EGFR (Epidermal Growth Factor Receptor) is a receptor that is activated when binding to epidermal growth factor. EGFR gene mutations are characteristic of a certain type of lung tumor.
Stage 2 of the study involves patients with locally advanced unresectable or metastatic triple-negative breast cancer who will receive a selected dose of the investigational product BCD-106.
PD-L1 is programmed cell death ligand 1.
The combined positive score is the ratio of the number of cells with PD-L1 expression in the tumor, lymphocytes, and macrophages to the total number of tumor cells, multiplied by 100.
BRCA genes (Breast Cancer Genes) are genes associated with susceptibility to breast cancer.
Cell surface glycoprotein, which plays a role in intercellular interaction, normally prevents the capture of normal red blood cells by phagocytic cells and suppresses the activity of the immune system.
Molecules that block signal regulatory protein alpha and prevent it from binding to CD47.
An investigational therapy is a treatment used in a clinical study.
The term “in situ”, translated from Latin as “in the original place”, is used in oncology to refer to a tumor in the initial stage of development.
RECIST (Response Evaluation Criteria in Solid Tumors) is a set of standardized criteria used to evaluate tumor shrinkage in response to therapy.
ECOG is a disease severity rating scale developed by the Eastern Cooperative Oncology Group.
Hemotransfusion is a blood transfusion, a particular type of transfusion in which the biological fluid transfused from the donor to the recipient is blood or its component. This process is one of the types of replacement therapy.