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

Last updated: March 13, 2024
Sponsor: R-Pharm
Overall Status: Active - Not Recruiting

Phase

3

Condition

Melanoma

Malignant Melanoma

Skin Cancer

Treatment

Keytruda®

RPH-075

Clinical Study ID

NCT06320353
CL01860211
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. A voluntarily signed and dated Informed Consent form (ICF) of the patient.
  2. Histologically verified (there are documented results of relevant studies, in theabsence of previous studies results, verification will be performed in the centrallaboratory) skin melanoma (patients with uveal melanoma or melanoma of the mucousmembranes are not included in the study).
  3. 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 antitumortherapy 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 thedrug used, before randomization (the drug will be used as a 1-line therapy);
  1. The Eastern Cooperative Oncology Group (ECOG) score 0-2.
  2. The presence of measurable control tumor foci (at least 1 focus), according to theResponse evaluation criteria in solid tumors (RECIST) 1.1, confirmed by the conclusionof the Blinded Independent Central Response Assessment Committee.
  3. Absence or resolution of toxic effects of previous therapy or negative consequences ofsurgical operations up to ≤ 2 grade according to Common Terminology Criteria forAdverse Events (CTCAE) 5.0, with the exception of chronic / irreversible adverseevents that do not affect the safety parameters of the studied therapy (for example,alopecia).
  4. Life expectancy is at least 12 weeks from the date of randomization (according to theResearcher assessment).
  5. Consent of female participants capable of childbirth, defined as all women with thephysiological ability to conceive (with the exception of women with the finalcessation of menstruation, which should be determined retrospectively after 12 monthsof natural amenorrhea, i.e. amenorrhea with an appropriate clinical status, forexample, a suitable age), to use highly effective methods of contraception, startingwith 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 thepresence of a negative pregnancy test result (chorionic gonadotropin test). Consent ofsexually active male participants in a clinical trial to use highly effective methodsof contraception, starting from the moment of signing the informed consent form andthroughout the study (for at least 28 days after the last infusion of pembrolizumab).

Exclusion

Exclusion Criteria:

  1. Severe concomitant diseases, with life-threatening, acutely developing complicationsof the underlying disease (including massive pleural, pericardial or peritonealeffusion requiring aspiration, requiring intervention, pulmonary lymphangitis).
  2. Metastases in the central nervous system, progressing or accompanied by clinicalsymptoms (for example, cerebral edema, spinal cord compression) or requiring the useof glucocorticosteroids (GCS) and/or anticonvulsants in doses specified in criterionNo. 6; Patients with brain metastases can be included in the study if they receiveadequate therapy (surgery or radiotherapy) and are stabilized by imaging studies forat least 4 weeks before the expected date of randomization into the study.
  3. Concomitant diseases that are ongoing at the time of the screening examination andthat increase the patient's risk of developing adverse events during the use of studytherapy:
  • stable exertional angina of functional class III-IV, unstable angina, or ahistory of myocardial infarction suffered less than 1 month before the expecteddate of randomization into the study;
  • clinically significant rhythm disturbances (patients with asymptomatic atrialfibrillation can be included in the study provided the ventricular rhythm iscontrolled);
  • chronic heart failure of classes III-IV according to the New York HeartAssociation (NYHA) classification;
  • uncontrolled arterial hypertension (systolic blood pressure above 150 mmHg ordiastolic blood pressure above 90 mmHg during antihypertensive therapy);
  • severe respiratory failure;
  • any other concomitant disease or condition that significantly increases the riskof developing adverse event (AE) during the study, in the opinion of theInvestigator.
  1. Systemic autoimmune diseases in the active phase (including, but not limited to:systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis (UC), systemicscleroderma, inflammatory myopathy, mixed forms of connective tissue diseases, overlapsyndrome, etc.), requiring systemic therapy for 2 years before expected date ofrandomization into the study.
  2. Endocrine disorders that cannot be compensated for by regular hormone replacementtherapy or other standard therapy at a constant dose for 28 days before the expecteddate of randomization into the study.
  3. The need for therapy with GCS and any other drugs that have an immunosuppressiveeffect (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 thatJAK inhibitor therapy has been completed for at least 1.5 months. Beforerandomization, 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 passedbefore the expected date of randomization into the study.
  4. Hematological disorders:
  • neutrophils < 1.5 x 10^9 /L,
  • platelets < 100 x 10^9 /L,
  • hemoglobin < 90 g/L.
  1. Renal dysfunction: • creatinine > 1.5 × Upper limit of normal (ULN) or glomerular filtration rate < 45ml/min.
  2. Impaired liver function :
  • bilirubin ≥ 1.5 × ULN (except for patients with Gilbert's syndrome, whose totalbilirubin values should not exceed 50 mmol/L),
  • Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) ≥ 2.5 × ULN (5 × ULN for patients with liver metastases),
  • Alkaline phosphatase ≥ 5 × ULN
  1. Conducting surgical treatment less than 28 days, radiation therapy less than 14 daysbefore the expected date of randomization into the study.
  2. Uveal melanoma or melanoma of the mucous membranes.
  3. Possibility of radical removal of all metastatic foci.
  4. Conducting 2 or more lines of systemic antitumor therapy for the underlying disease. (Prior therapy with targeted drugs (Serine/threonine-protein kinase B-raf (BRAF)/Mitogen-activated protein kinase (MEK) inhibitors, c-KIT (CD117) inhibitors) isallowed as 1st line therapy)
  5. Previous therapy with pembrolizumab and other anti- Programmed cell death 1 (PD-1)/PD-L1/Programmed Cell Death 1 Ligand 2 (PD-L2) drugs.
  6. The presence of another oncological pathology that is progressing or requiresantitumor therapy (including hormonal) within 5 years before signing the ICF, with theexception of radically removed cervical carcinoma in situ, radically removed breastcancer in situ or radically removed basal cell/ squamous cell skin carcinoma.
  7. Conditions that limit the patient's ability to comply with the requirements of theprotocol (dementia, neurological or psychiatric disorders, drug and alcohol addiction,etc.).
  8. Concurrent participation in other interventional clinical trials, participation inother clinical trials less than 30 days before signing the ICF (provided the patienthas received at least one administration of experimental therapy), as well as previousparticipation in this clinical trial (provided the patient has received at least oneadministration of the drug RPH-075).
  9. Acute infectious diseases or activation of chronic infectious diseases less than 28days before the expected date of randomization into the study.
  10. Active hepatitis B, hepatitis C, human immunodeficiency viruses (HIV) infection.
  11. Therapy with live vaccines during the period 30 days before the expected date ofrandomization into the study. For patients receiving therapy with approvedsevere-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV2) vaccines,instructions for use and/or local requirements should be followed. The use of theSputnik V vaccine is acceptable, provided that at least 7 days have passed from themoment of administration of the second component of the vaccine to the firstadministration of the study drug).
  12. History of interstitial lung disease (non-infectious nature)/pneumonitis requiring theuse of steroid therapy, current pneumonitis/Interstitial lung disease (ILD).
  13. Impossibility of intravenous administration of the study drug.
  14. Impossibility of intravenous contrast.
  15. Hypersensitivity (grade 3 or more) to any of the components of the drugRPH-075/Keytruda®.
  16. History of hypersensitivity to monoclonal antibody drugs.
  17. Pregnancy or breastfeeding.
  18. The presence of any other significant concomitant diseases or conditions that could,in the reasonable opinion of the study physician, adversely affect the patient'sparticipation and well-being in the study and/or distort the evaluation of the studyresults.

Study Design

Total Participants: 266
Treatment Group(s): 2
Primary Treatment: Keytruda®
Phase: 3
Study Start date:
September 27, 2023
Estimated Completion Date:
January 31, 2026

Study Description

This study will include the following periods:

  1. Screening period (before the first administration of the test drug). Before being included in the study, patients will be provided with complete information about this clinical trial, its objectives, as well as the risks associated with participating in it, as set out in the patient information sheet.

    After the patient signs the Informed consent Form (IF), he will be examined as part of the screening period, at the end of which the researcher will decide whether or not the patient can be randomized into the study.

  2. Main period (days: 1 - 168) Patients who meet the selection criteria will be randomized in a 1:1 ratio to one of the two study groups: RPH-075 and Keytruda®.

    Patients will receive pembrolizumab (RPH-075 or Keytruda®) in a monotherapy regimen, at a dose of 200 mg, intravenously, with a frequency of once every 3 weeks (3 weeks - 1 cycle).

    Therapy within the Main Study period will continue until (whichever comes first):

    • 24 weeks (8 cycles, 168 days);

    • disease progression (according to the Immune-Related Response Evaluation Criteria In Solid Tumors (iRECIST)/clinical progression);

    • the development of phenomena of intolerable toxicity.

    The assessment of tumor response to the therapy at this step will be carried out every 12 weeks.

  3. Continued therapy period (days: 169 - 365) During the period of continued therapy, all patients will receive therapy with RPH-075, including those patients who received therapy with Keytruda® during the Main Study Period. Pembrolizumab will be administered intravenously, at a dose of 200 mg, with a frequency of once every 3 weeks. In case of significant AEs, pembrolizumab therapy may be postponed for up to 12 weeks.

    Therapy within the period of continued therapy will be carried out until (whichever comes first):

    • a period of up to 1 year;

    • before the disease progression (according to the criteria of iRECIST /clinical progression);

    • the development of phenomena of intolerable toxicity.

    The assessment of tumor response to the therapy at this step will be carried out every 12 weeks.

  4. The period of further treatment (days: 366-730]) Participants in this period will be patients who, after 1 year of therapy, will have a stabilization of the disease or a tumor response to therapy. The decision to switch to this period wil be made by the researcher. If, according to the decision of the researcher, the patient will not be recommended to switch to this period, then the patient goes into the Follow-up Period.

    During the the period of further treatment patients will receive therapy with RPH-075 according to the same scheme as in the period of Continued therapy.

    Therapy within the Period will be carried out until (whichever comes first):

    • a total period of up to 2 years; all examinations will be carried out within the framework of routine clinical practice;

    • before the disease progression;

    • the development of phenomena of intolerable toxicity. All examinations necessary for the patient, including radiation diagnostics, and concomitant therapy during the Period will be carried out within the framework of routine clinical practice and through the healthcare system, with the exception of visits where therapy will be administered (every 3 weeks). Also, during these visits, data on the AEs and occurrence of events (progression) will be collected.

  5. Follow-up period (FU)

For patients who will have completed their planned participation, namely:

  • The period of further treatment,

  • The period of continued therapy (those patients who will not be transferred during the pre-treatment Period),

one follow-up visit (FU-visit) will be scheduled 28 ± 3 days after the last administration.

For patients who will complete therapy ahead of schedule (within the Main period or the Period of continued therapy), due to the progression of the disease or the development of intolerant toxicity phenomena, FU visits will be conducted with a multiplicity of 1 every 12 weeks until the Day 365 of the study.

All examinations and concomitant therapy during the Follow-up Period will be provided through the health care system (as a part of routine clinical practice), with the exception of a radiation diagnostic visit conducting to assess the response (every 12 weeks).

The total expected duration of the study is approximately 3 years. The expected duration of participation of each subject is approximately 26 months (about 2 years).

Connect with a study center

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

    Obninsk, Kaluga Region 249036
    Russian Federation

    Site Not Available

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

    Krasnodar, Krasnodar Territory 350040
    Russian Federation

    Site Not Available

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

    Kislino, Kursk Region 305524
    Russian Federation

    Site Not Available

  • 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 Region 143515
    Russian Federation

    Site Not Available

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

    Pyatigorsk, Stavropol Territory 357502
    Russian Federation

    Site Not Available

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

    Ekaterinburg, Sverdlovsk Region 620036
    Russian Federation

    Site Not Available

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

    Ufa, The Republic Of Bashkortostan 450054
    Russian Federation

    Site Not Available

  • 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
    Russian Federation

    Site Not Available

  • 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
    Russian Federation

    Site Not Available

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

    Arkhangelsk, 163045
    Russian Federation

    Site Not Available

  • State Budgetary Healthcare Institution "Regional Oncological Dispensary"

    Irkutsk, 664035
    Russian Federation

    Site Not Available

  • Regional budgetary healthcare institution "Ivanovo Regional Oncological Dispensary"

    Ivanovo, 153040
    Russian Federation

    Site Not Available

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

    Kaluga, 248007
    Russian Federation

    Site Not Available

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

    Kemerovo, 650036
    Russian Federation

    Site Not Available

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

    Krasnoyarsk, 660133
    Russian Federation

    Site Not Available

  • "Moscow Center for Rehabilitation Treatment" LLC

    Moscow, 121552
    Russian Federation

    Site Not Available

  • "Research lab" LLC

    Moscow, 127521
    Russian Federation

    Site Not Available

  • Branch Office of "Hadassah Medical Ltd"

    Moscow, 121205
    Russian Federation

    Site Not Available

  • 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
    Russian Federation

    Site Not Available

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

    Moscow, 115478
    Russian Federation

    Site Not Available

  • Medsi Group of Companies JSC

    Moscow, 123056
    Russian Federation

    Site Not Available

  • 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
    Russian Federation

    Site Not Available

  • 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
    Russian Federation

    Site Not Available

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

    Nizhny Novgorod, 603126
    Russian Federation

    Site Not Available

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

    Novosibirsk, 630108
    Russian Federation

    Site Not Available

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

    Omsk, 644013
    Russian Federation

    Site Not Available

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

    Perm, 614066
    Russian Federation

    Site Not Available

  • "Euro Cityclinic" LLC

    Saint Petersburg, 197022
    Russian Federation

    Site Not Available

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

    Saint Petersburg, 195271
    Russian Federation

    Site Not Available

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

    Saint Petersburg, 197022
    Russian Federation

    Site Not Available

  • State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital

    Saint Petersburg, 188300
    Russian Federation

    Site Not Available

  • State Budgetary Healthcare Institution "Samara Regional Clinical Oncological Dispensary"

    Samara, 443031
    Russian Federation

    Site Not Available

  • State Healthcare Institution "Regional Clinical Oncological Dispensary"

    Saratov, 410053
    Russian Federation

    Site Not Available

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

    Smolensk, 214000
    Russian Federation

    Site Not Available

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

    Tomsk, 634050
    Russian Federation

    Site Not Available

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

    Tyumen, 625041
    Russian Federation

    Site Not Available

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.