Study сomparing the Efficacy and Safety of RPH-075 and Keytruda® in Patients With Unresectable or Metastatic Skin Melanoma

NCT06320353 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: CL01860211
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 36

Brief Summary

The goal of this double-blind, randomized study is to establish the equivalence of the efficacy, safety and immunogenicity of the drugs RPH-075 (international nonproprietary name (INN) is pembrolizumab) and Keytruda® (INN is pembrolizumab) when used in patients with unresectable or metastatic skin melanoma first or second line therapy in a monotherapy regimen. The main task is to evaluate and compare the effectiveness of RPH-075 and Keytruda® drugs when used in patients with unresectable or metastatic skin melanoma as a 1 or 2 line therapy in monotherapy regimen, according to the objective response rate (ORR) parameter for up to 24 weeks of therapy.

Conditions

Skin Melanoma

Keywords

cancer; melanoma

Outcome Measures

Primary Outcomes (1)

• The objective response rate (ORR)

  The objective response rate parameter (ORR) is the percentage of patients in a particular group who experienced a complete or partial tumor response to therapy during treatment, according to the criteria of Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. The complete response (CR) is the disappearance of all control lesions, confirmed by Computed tomography (CT) data for at least 4 weeks; the short diameter of any lymph node previously considered pathological (control or non-control) should be \< 10 mm. The partial response (PR) is a decrease in the sum of the diameters of the control foci by 30% or more for at least 4 weeks, compared with the initial sum of the diameters of the foci (at screening).

  up to 24 weeks

Secondary Outcomes (4)

• The disease control rate (DCR)

  up to 24 weeks

• The time to response (TTR)

  from the start of study therapy to the first tumor response to therapy, up to 24 weeks

• The Duration of response (DOR)

  from the first tumor response to therapy to the disease progression, up to 24 weeks

• The Progression-free survival (PFS)

  up to 12 months

Study Arms (2)

RPH-075

EXPERIMENTAL

Pembrolizumab will be administered as an intravenous infusion every 3 weeks, at a fixed dose of 200 mg, for 30 minutes (it is permissible, but not desirable, to carry out an infusion in the range from 25 to 40 minutes). Premedication before administration of pembrolizumab is not mandatory.

Drug: RPH-075

Keytruda®

ACTIVE COMPARATOR

Pembrolizumab will be administered as an intravenous infusion every 3 weeks, at a fixed dose of 200 mg, for 30 minutes (it is permissible, but not desirable, to carry out an infusion in the range from 25 to 40 minutes). Premedication before administration of pembrolizumab is not mandatory.

Drug: Keytruda®

Interventions

RPH-075 DRUG

100 mg/4 mL (25 mg/mL) concentrate for solution for infusions in a single-dose vial The required volume (8 ml) of the Drug concentrate solution should be withdrawn from the vials and transferred into an intravenous bag containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection. (The final concentration of the diluted solution should be between 1 mg/mL to 10 mg/mL.)

Also known as: pembrolizumab, Arfleyda

RPH-075

Keytruda® DRUG

100 mg/4 mL (25 mg/mL) concentrate for solution for infusions in a single-dose vial The required volume (8 ml) of the Drug concentrate solution should be withdrawn from the vials and transferred into an intravenous bag containing 0.9% Sodium Chloride Injection or 5% Dextrose Injection. (The final concentration of the diluted solution should be between 1 mg/mL to 10 mg/mL.)

Also known as: pembrolizumab

Keytruda®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A voluntarily signed and dated Informed Consent form (ICF) of the patient.
• Histologically verified (there are documented results of relevant studies, in the absence of previous studies results, verification will be performed in the central laboratory) skin melanoma (patients with uveal melanoma or melanoma of the mucous membranes are not included in the study).
• The following patient populations:
• with skin melanoma:
• newly diagnosed, previously untreated, unresectable (stage III) or metastatic (stage IV) (the drug will be used as a 1st line therapy);
• unresectable or metastatic, with progression during or after systemic antitumor therapy of the 1st line (the drug will be used as a therapy of the 2nd line);
• with progression after previously performed neoadjuvant /adjuvant therapy, provided that the therapy was completed in a time exceeding 5 half-lives of the drug used, before randomization (the drug will be used as a 1-line therapy);
• The Eastern Cooperative Oncology Group (ECOG) score 0-2.
• The presence of measurable control tumor foci (at least 1 focus), according to the Response evaluation criteria in solid tumors (RECIST) 1.1, confirmed by the conclusion of the Blinded Independent Central Response Assessment Committee.
• Absence or resolution of toxic effects of previous therapy or negative consequences of surgical operations up to ≤ 2 grade according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0, with the exception of chronic / irreversible adverse events that do not affect the safety parameters of the studied therapy (for example, alopecia).
• Life expectancy is at least 12 weeks from the date of randomization (according to the Researcher assessment).
• Consent of female participants capable of childbirth, defined as all women with the physiological ability to conceive (with the exception of women with the final cessation of menstruation, which should be determined retrospectively after 12 months of natural amenorrhea, i.e. amenorrhea with an appropriate clinical status, for example, a suitable age), to use highly effective methods of contraception, starting with from the moment of signing the informed consent form and throughout the study (for at least 28 days after the last infusion of pembrolizumab) as well as the presence of a negative pregnancy test result (chorionic gonadotropin test). Consent of sexually active male participants in a clinical trial to use highly effective methods of contraception, starting from the moment of signing the informed consent form and throughout the study (for at least 28 days after the last infusion of pembrolizumab).

You may not qualify if:

• Severe concomitant diseases, with life-threatening, acutely developing complications of the underlying disease (including massive pleural, pericardial or peritoneal effusion requiring aspiration, requiring intervention, pulmonary lymphangitis).
• Metastases in the central nervous system, progressing or accompanied by clinical symptoms (for example, cerebral edema, spinal cord compression) or requiring the use of glucocorticosteroids (GCS) and/or anticonvulsants in doses specified in criterion No. 6; Patients with brain metastases can be included in the study if they receive adequate therapy (surgery or radiotherapy) and are stabilized by imaging studies for at least 4 weeks before the expected date of randomization into the study.
• Concomitant diseases that are ongoing at the time of the screening examination and that increase the patient's risk of developing adverse events during the use of study therapy:
• stable exertional angina of functional class III-IV, unstable angina, or a history of myocardial infarction suffered less than 1 month before the expected date of randomization into the study;
• clinically significant rhythm disturbances (patients with asymptomatic atrial fibrillation can be included in the study provided the ventricular rhythm is controlled);
• chronic heart failure of classes III-IV according to the New York Heart Association (NYHA) classification;
• uncontrolled arterial hypertension (systolic blood pressure above 150 mmHg or diastolic blood pressure above 90 mmHg during antihypertensive therapy);
• severe respiratory failure;
• any other concomitant disease or condition that significantly increases the risk of developing adverse event (AE) during the study, in the opinion of the Investigator.
• Systemic autoimmune diseases in the active phase (including, but not limited to: systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis (UC), systemic scleroderma, inflammatory myopathy, mixed forms of connective tissue diseases, overlap syndrome, etc.), requiring systemic therapy for 2 years before expected date of randomization into the study.
• Endocrine disorders that cannot be compensated for by regular hormone replacement therapy or other standard therapy at a constant dose for 28 days before the expected date of randomization into the study.
• The need for therapy with GCS and any other drugs that have an immunosuppressive effect (at a dose equivalent to the daily use of prednisolone at a dose of \>10 mg); the use of inhaled/topical drugs GCS is allowed; patients receiving Janus kinase (JAK) inhibitor therapy for coronavirus infection can be included in the study provided that JAK inhibitor therapy has been completed for at least 1.5 months. Before randomization, patients treated with anti-IL-6 drugs can be included in the study, provided that at least 5 half-lives of the anti-Interleukin 6 (IL-6) drug have passed before the expected date of randomization into the study.
• Hematological disorders:
• neutrophils \< 1.5 x 10\^9 /L,
• platelets \< 100 x 10\^9 /L,

Sponsors & Collaborators

• R-Pharm: lead
• Data Management 365: collaborator
• Exacte Labs LLC: collaborator
• Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor: collaborator

Study Sites (36)

Federal State Budgetary Institution "National Medical Research Center of Radiology" of the Ministry of Health of the Russian Federation

Obninsk, Kaluga Oblast, 249036, Russia

Location

State Budgetary Healthcare Institution "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar Territory

Krasnodar, Krasnodar Territory, 350040, Russia

Location

Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G.E. Ostroverkhov"

Kislino, Kursk Oblast, 305524, Russia

Location

State Budgetary Healthcare Institution of the city of Moscow "Moscow City Oncological Hospital No. 62 of the Department of Health of the City of Moscow"

Istra, Moscow Oblast, 143515, Russia

Location

The State budgetary healthcare Institution of the Stavropol Territory "Pyatigorsk Interdistrict Oncological Dispensary"

Pyatigorsk, Stavropol Territory, 357502, Russia

Location

The State Autonomous Healthcare Institution of the Sverdlovsk region "Sverdlovsk Regional Oncological Dispensary"

Yekaterinburg, Sverdlovsk Oblast, 620036, Russia

Location

State Autonomous Healthcare Institution Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan

Ufa, The Republic of Bashkortostan, 450054, Russia

Location

State Autonomous Healthcare Institution "Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z.Segal"

Kazan', The Republic of Tatarstan, 420029, Russia

Location

Budgetary Healthcare Institution of the Udmurt Republic "Sergey Grigoryevich Primushko Republican Clinical Oncological Dispensary of the Ministry of Health of the Udmurt Republic"

Izhevsk, Udmurt Republic, 426009, Russia

Location

State Budgetary Healthcare Institution of the Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, 163045, Russia

Location

State Budgetary Healthcare Institution "Regional Oncological Dispensary"

Irkutsk, 664035, Russia

Location

Regional budgetary healthcare institution "Ivanovo Regional Oncological Dispensary"

Ivanovo, 153040, Russia

Location

Kaluga Region State Budgetary Healthcare Institution "Kaluga Regional Clinical Oncological Dispensary"

Kaluga, 248007, Russia

Location

State Budgetary healthcare Institution "Kuzbass Clinical Oncological Dispensary named after M.S. Rappoport"

Kemerovo, 650036, Russia

Location

Regional State Budgetary Healthcare Institution "Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky"

Krasnoyarsk, 660133, Russia

Location

State Budgetary Institution of healthcare of the city of Moscow "Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Healthcare of the City of Moscow"

Moscow, 108814, Russia

Location

Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation

Moscow, 115478, Russia

Location

State Budgetary Healthcare Institution of the city of Moscow "City Clinical Oncological Hospital No. 1 of the Department of Health of the City of Moscow"

Moscow, 117152, Russia

Location

Federal State Autonomous Education Insitution of High Education the First Moscow State Medical University named after I.M. Sechenov of Ministry of Healthcare of Russian Federation (Sechenov University)

Moscow, 119991, Russia

Location

Branch Office of "Hadassah Medical Ltd"

Moscow, 121205, Russia

Location

"Moscow Center for Rehabilitation Treatment" LLC

Moscow, 121552, Russia

Location

Medsi Group of Companies JSC

Moscow, 123056, Russia

Location

"Research lab" LLC

Moscow, 127521, Russia

Location

State Budgetary Healthcare Institution of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Oncological Dispensary"

Nizhny Novgorod, 603126, Russia

Location

State Budgetary Healthcare Institution of the Novosibirsk region "Novosibirsk Regional Clinical Oncological Dispensary"

Novosibirsk, 630108, Russia

Location

Budgetary healthcare institution of the Omsk region "Clinical Oncological Dispensary"

Omsk, 644013, Russia

Location

State Budgetary Healthcare Institution of the Perm Territory "Perm Regional Oncological Dispensary"

Perm, 614066, Russia

Location

State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital

Saint Petersburg, 188300, Russia

Location

Private healthcare institution "Clinical Hospital "Russian Railways-Medicine" of the city of St. Petersburg"

Saint Petersburg, 195271, Russia

Location

"Euro Cityclinic" LLC

Saint Petersburg, 197022, Russia

Location

St. Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"

Saint Petersburg, 197022, Russia

Location

State Budgetary Healthcare Institution "Samara Regional Clinical Oncological Dispensary"

Samara, 443031, Russia

Location

State Healthcare Institution "Regional Clinical Oncological Dispensary"

Saratov, 410053, Russia

Location

Regional State Budgetary Healthcare Institution "Smolensk Regional Oncological Clinical Dispensary"

Smolensk, 214000, Russia

Location

Siberian State Medical University of the Ministry of Healthcare of Russian Federation

Tomsk, 634050, Russia

Location

The State Autonomous healthcare Institution of the Tyumen region "Multidisciplinary clinical Medical Center "Medical City"

Tyumen, 625041, Russia

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 20, 2024
• Study Start: September 27, 2023
• Primary Completion: June 1, 2024
• Study Completion: January 1, 2026
• Last Updated: March 20, 2024

Record last verified: 2024-03

Locations

RU (36)