Clinical trial NCT06640530: Clinical Study of the Efficacy 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 Efficacy and Safety of BCD-263 and Opdivo® As Monotherapy in Subjects with Advanced Melanoma of the Skin
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Melanoma
Melanoma (Skin)
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2024-10-15
Enrollment: 392
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-263-2/UNIVERSE is to demonstrate comparable efficacy and similar safety and immunogenicity profile of BCD-263 and Opdivo after repeated intravenous doses in subjects with advanced unresectable or metastatic melanoma of the skin.

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. Signed informed consent and the subject's ability to comply with the protocol requirements.
2. Age ≥18 years at the time of signing the informed consent form.
3. Histologically confirmed melanoma with the following prognostic characteristics:

   * LDH \<ULN of local laboratory (enrollment of subjects with LDH \<2 x 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.
5. Presence of a tumor sample (archived or new biopsy) that is suitable for evaluation for PD L1 expression in the Investigator's opinion.
6. At least one measurable lesion as per RECIST 1.1 based on independent central review.
7. ECOG score 0-1.
8. Laboratory test results consistent with adequate functioning of systems and organs.

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.
4. Active CNS metastases and/or carcinomatous meningitis.
5. Previous invasive cancer, excluding diseases treated with potentially radical 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.
8. Active, known or suspected autoimmune disorders (subjects with type 1 diabetes mellitus or hypothyroidism requiring only hormone-replacement therapy and those with skin disorders \[vitiligo, alopecia, or psoriasis\] not requiring systemic therapy are eligible to participate).
9. The need for systemic corticosteroids (at doses equivalent to \>10 mg/day prednisolone) or any other immunosuppressive drugs within 14 days prior to randomization. The use of inhaled and topical corticosteroids is allowed.
10. History of (non-infectious) pneumonitis requiring corticosteroid therapy or pneumonitis at the time of screening.
11. Any anticancer therapy or major surgery within 28 days prior to randomization, or the subject's AE (other than alopecia) caused by anticancer therapy has not yet recovered to CTCAE grade 1 or has not completely resolved.
12. Concomitant use of drugs or medical devices studied in other clinical studies or their use within 28 days prior to randomization.
13. Infections requiring therapy or systemic antibiotics within 14 days prior to randomization.
14. Administration of a live and/or attenuated vaccine within 28 days prior to randomization.
15. Positive HIV-1 or HIV-2 test.
16. HBV/HCV infections (subjects with a negative PCR result for hepatitis C virus RNA, without significant abnormalities in blood chemistry tests, examined by an infectious disease specialist and not requiring specific antiviral treatment at the time of screening, may be included in the study. Subjects with a positive HbsAg test result cannot be included in the study).
17. Impossibility to administer intravenous contrast agents (including due to hypersensitivity to contrast media).
18. Hypersensitivity or allergy to any of the nivolumab product components. Hypersensitivity or allergy to medicinal products obtained based on Chinese hamster ovary cells, or history of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or hybrid proteins.
19. Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period.

Primary outcomes:
measure: Overall response rate (ORR) according to RECIST 1.1
timeFrame: Week 25
Secondary outcomes:
measure: Time to response
timeFrame: Week 25
measure: Duration of response
timeFrame: week 25
measure: DCR
timeFrame: week 25
measure: PFS
timeFrame: week 25
measure: Overall survival
timeFrame: week 25
measure: Safety assessment
timeFrame: Through week 105
measure: Immunogenicity assessment
timeFrame: Through week 105
Other outcomes:
measure: AUC(0-∞) (optional)
timeFrame: week 25
measure: AUC(0-672) of nivolumab (optional)
timeFrame: week 25
measure: Cmax (optional)
timeFrame: week 25
measure: Tmax (optional)
timeFrame: week 25
measure: T½ (optional)
timeFrame: week 25
measure: Kel (optional)
timeFrame: week 25
measure: Vd (optional)
timeFrame: week 25
measure: Cl (optional)
timeFrame: week 25
measure: Ceoi (optional)
timeFrame: week 25
measure: Cmin (optional)
timeFrame: week 25
measure: Cmax, ss (optional)
timeFrame: week 25
measure: Ctrough, ss (optional)
timeFrame: week 25
measure: Ctrough (optional)
timeFrame: week 25
Locations:
city: Brest
country: Belarus
facility: Healthcare Institution "Brest Regional Oncological Dispensary"
city: Gomel
country: Belarus
facility: Health Institution "Gomel Regional Clinical Oncology Center"
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: Islamabad
country: Pakistan
facility: Shaheed Zulfiqar Ali Bhutto Medical University
city: Peshawar
country: Pakistan
facility: Rehman Medical Institute
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Center for Oncology and Nuclear Medicine
state: Chelyabinsk Oblast
city: Krasnodar
country: Russian Federation
facility: Clinical Oncologic Dispensary No. 1
state: Krasnodar Kari
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky
state: Krasnoyarsk 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: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Oncology Center
city: Ivanovo
country: Russian Federation
facility: Ivanovo Regional Oncology Center
city: Izhevsk
country: Russian Federation
facility: State Health Care Institution "Republican Clinical Cancer Center," the Ministry of Health of the Udmurt Republic
city: Kaliningrad
country: Russian Federation
facility: State Budgetary Health Institution "Regional Clinical Hospital of Kaliningrad Region"
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: 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: 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: Moscow
country: Russian Federation
facility: State Budgetary Institution of Healthcare of the City of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Health of the City of Moscow"
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 "Novosibirsk Regional Clinical Oncology Center" of the Novosibirsk Region
city: Omsk
country: Russian Federation
facility: State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
city: Perm
country: Russian Federation
facility: Perm Region Oncology Dispensary
city: Perm
country: Russian Federation
facility: State Budgetary Healthcare Institution of Perm Krai "Order of Honour" Perm Regional Clinical Hospital "
city: Rostov-on-Don
country: Russian Federation
facility: Federal Government Budgetary Institution "National Institute of Cancer Research" of Ministry of Health of Russian Federation
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 Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncological)
city: Saint Petersburg
country: Russian Federation
facility: JSC "North-West Centre of Evidence-Based Mediccine"
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: Smolensk
country: Russian Federation
facility: Provincial health official body "Smolensk Regional Clinical Oncological Dispensary"
city: Tomsk
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation
city: Tver
country: Russian Federation
facility: Federal State Budgetary Institution of Health "Tver Regional Clinical Oncological Dispensary" of the Tver Region
city: Tyumen
country: Russian Federation
facility: State Autonomus Institution of Health "Mulitiprofile Clinical Medical Centre "Medical City""
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:
References: