Clinical trial NCT06112808: A Clinical Study of the Pharmacokinetics and Safety of BCD-263 and Opdivo® as Monotherapy in Subjects With Advanced Melanoma of the Skin
Official title: A Double-Blind, Randomized Clinical Study of the Pharmacokinetics and Safety of BCD-263 and Opdivo® as Monotherapy in Subjects With Advanced Melanoma of the Skin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Melanoma
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2023-11-02
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study BCD-263-1 is to prove the comparability of the pharmacokinetics and similarity of the safety, immunogenicity and pharmacodynamic profiles of BCD-263 and Opdivo following intravenous administration to subjects with advanced unresectable or metastatic melanoma of the skin. The study will have randomized, double-blind design with parallel assignment.

Detailed description: Following screening, subjects will be randomized to receive either BCD-263 or Opdivo in a 1:1 ratio and enter the main study period.

During the main study period, subjects will receive therapy with BCD-263 or Opdivo, which will be administered intravenously until disease progression or signs of unacceptable toxicity develop (whichever occurs earlier).

At Week 25, after completion of all scheduled procedures subjects in both groups will continue to receive open-label BCD-263 for up to a total of 2 years of therapy, or disease progression, or signs of unacceptable toxicity (whichever occurs first).

Following discontinuation of the study therapy, the subjects will enter a follow-up period, during which data on overall survival will be collected through telephone contacts.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form;
2. Body weight 60 to 90 kg.
3. Histologically confirmed melanoma with the following prognostic characteristics:

   * LDH \<ULN of local laboratory (enrollment of subjects with LDH \<2x ULN of local laboratory is allowed until the number of subjects with LDH \>ULN is 30% of the total population of randomized subjects. The Sponsor will inform when enrollment of subjects is limited by LDH level \<ULN of the local laboratory).
   * Absence, according to the Investigator, of clinically significant symptoms associated with the tumor.
   * Absence, according to the Investigator, of rapidly progressing metastatic melanoma.
4. Newly diagnosed advanced unresectable (stage III) or metastatic disease (stage IV), or progressive disease during / relapsing after radical treatment.

Exclusion Criteria:

1. Indications for radical treatment (surgery, radiation therapy).
2. Uveal or mucosal melanoma.
3. Previous systemic anticancer therapy for advanced unresectable or metastatic skin melanoma (a history of neoadjuvant or adjuvant therapy is allowed, provided that the therapy was completed at least 12 weeks before randomization).
4. Active CNS metastases and/or carcinomatous meningitis.
5. Previous invasive cancer, excluding diseases treated with potentially curative therapy with no evidence of recurrence for 2 years from the start of this therapy (subjects with radically resected basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, cervical carcinoma in situ of the uterus and other carcinomas in situ may be included).
6. Subjects with severe concomitant disorders, life-threatening acute complications of the primary disease (including massive pleural, pericardial, or peritoneal effusions requiring intervention, pulmonary lymphangitis, bleeding or organ perforation) at the time of signing the informed consent and during the screening period.
7. Concomitant diseases and/or conditions that significantly increase the risk of adverse events (AEs) during the study.

Primary outcomes:
measure: AUC(0-672) of nivolumab
timeFrame: pre-dose to week 25
Secondary outcomes:
measure: Cmax
timeFrame: week 25
measure: AUC(0-∞)
timeFrame: week 25
measure: Tmax
timeFrame: week 25
measure: T½
timeFrame: week 25
measure: Kel
timeFrame: week 25
measure: Vd
timeFrame: week 25
measure: Cl
timeFrame: week 25
measure: Ceoi
timeFrame: week 25
measure: Ctrough
timeFrame: week 25
measure: Safety assessment
timeFrame: week 25
measure: Immunogenicity assessment
timeFrame: week 25
measure: Pharmacodynamics assessment
timeFrame: week 25
measure: Efficacy assessment: ORR
timeFrame: week 25
measure: Efficacy assessment: PFS
timeFrame: week 25
measure: Efficacy assessment: overall survival
timeFrame: week 25
measure: Efficacy assessment: DCR
timeFrame: week 25
measure: Efficacy assessment: time to response
timeFrame: week 25
measure: Efficacy assessment: duration of response
timeFrame: week 25
Other outcomes:
Locations:
city: Minsk
country: Belarus
facility: Healthcare Institution "Minsk City Clinical Cancer Center"
city: Minsk
country: Belarus
facility: State Institution "Republic Scientific and Practical Centre for Oncology and Medical Radiology Named after N.N.Aleksandrov"
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
state: Chelyabinsk Oblast
city: Pyatigorsk
country: Russian Federation
facility: LLC "New Clinic"
state: Stavropol Krai
city: Arkhangel'sk
country: Russian Federation
facility: State Budgetary Institution of Healthcare of the Arkhangelsk Region "Severodvinsk City Hospital №2 of Emergency"
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"
city: Kaliningrad
country: Russian Federation
facility: Federal State Educational Institution of Higher Education "Baltic Federal University Named after Immanuel Kant"
city: Kaliningrad
country: Russian Federation
facility: Limited Liability Company "Ars Medica Centre"
city: Kaluga
country: Russian Federation
facility: State Budgetary Healthcare Institution of Kaluga Region "Kaluga Region Clinical Oncological Dispensary"
city: Kazan
country: Russian Federation
facility: State Autonomous Health Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
city: Kostroma
country: Russian Federation
facility: Regional State Budgetary of Healthcare Insti-tution "Kostroma Clinical Oncology Dispensary"
city: Moscow
country: Russian Federation
facility: "Russian Cancer Research Center named after N.N. Blokhin "of the Ministry of Health of the Russian Federation
city: Moscow
country: Russian Federation
facility: JSC "Medsi Group"
city: Moscow
country: Russian Federation
facility: Moscow City Oncology Hospital No. 62
city: Moscow
country: Russian Federation
facility: State budgetary health care institution of the city of Moscow "City Clinical Oncology Hospital No. 1 of the Department of Health of the City of Moscow"
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution "Moscow Clinical Scientific Center funded by Moscow Health Department" (SBHI MCSC MHD)
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Region State Budgetary Healthcare Institution "Nizhny Novgorod Regional Clinical Oncological Dispensary"
city: Novosibirsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Region Clinical Oncological Dispensary"
city: Omsk
country: Russian Federation
facility: State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: JSC "Modern Medical Technologies"
city: Saint Petersburg
country: Russian Federation
facility: Private healthcare institution "Clinical hospital "RZD-Medicine" of the city of Saint Petersburg"
city: Saint Petersburg
country: Russian Federation
facility: "Saint Petersburg Clinical Research and Practice Center for Specialized Medical Care (Oncology)"
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Oncological Research Center"
city: Saint Petersburg
country: Russian Federation
facility: Private Medical Institution Evromedservis
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution "N.N. Petrov Research Institute of Oncology" of the Ministry of Healthcare of the Russian Federation
city: Samara
country: Russian Federation
facility: State-financed Health Institution "Samara Region Clinical Oncology Dispensary"
city: Saransk
country: Russian Federation
facility: Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
city: Tomsk
country: Russian Federation
facility: Limited Liability Company "Nebbiolo"
city: Ufa
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Health republic Bashkortostan
city: Volgograd
country: Russian Federation
facility: State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
Study officials:
affiliation: Director of Clinical Development Department, BIOCAD
name: Arina V Zinkina-Orikhan
role: STUDY_DIRECTOR
References: