Trial Title:
Study сomparing the Efficacy and Safety of RPH-075 and Keytruda® in Patients With Unresectable or Metastatic Skin Melanoma
NCT ID:
NCT06320353
Condition:
Skin Melanoma
Conditions: Official terms:
Melanoma
Melanoma, Cutaneous Malignant
Skin Neoplasms
Pembrolizumab
Conditions: Keywords:
cancer
melanoma
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Double (Participant, Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
RPH-075
Description:
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The required volume (8 ml) of the Drug concentrate solution should be withdrawn from the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.)
Arm group label:
RPH-075
Other name:
pembrolizumab
Other name:
Arfleyda
Intervention type:
Drug
Intervention name:
Keytruda®
Description:
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The required volume (8 ml) of the Drug concentrate solution should be withdrawn from the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.)
Arm group label:
Keytruda®
Other name:
pembrolizumab
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.
Detailed 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).
Criteria for eligibility:
Criteria:
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 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).
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 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);
4. The Eastern Cooperative Oncology Group (ECOG) score 0-2.
5. 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.
6. 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).
7. Life expectancy is at least 12 weeks from the date of randomization (according to
the Researcher assessment).
8. 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).
Exclusion Criteria:
1. 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).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Hematological disorders:
- neutrophils < 1.5 x 10^9 /L,
- platelets < 100 x 10^9 /L,
- hemoglobin < 90 g/L.
8. Renal dysfunction:
• creatinine > 1.5 × Upper limit of normal (ULN) or glomerular filtration rate < 45
ml/min.
9. Impaired liver function :
- bilirubin ≥ 1.5 × ULN (except for patients with Gilbert's syndrome, whose total
bilirubin 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
10. Conducting surgical treatment less than 28 days, radiation therapy less than 14 days
before the expected date of randomization into the study.
11. Uveal melanoma or melanoma of the mucous membranes.
12. Possibility of radical removal of all metastatic foci.
13. 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)
is allowed as 1st line therapy)
14. Previous therapy with pembrolizumab and other anti- Programmed cell death 1
(PD-1)/PD-L1/Programmed Cell Death 1 Ligand 2 (PD-L2) drugs.
15. The presence of another oncological pathology that is progressing or requires
antitumor therapy (including hormonal) within 5 years before signing the ICF, with
the exception of radically removed cervical carcinoma in situ, radically removed
breast cancer in situ or radically removed basal cell/ squamous cell skin carcinoma.
16. Conditions that limit the patient's ability to comply with the requirements of the
protocol (dementia, neurological or psychiatric disorders, drug and alcohol
addiction, etc.).
17. Concurrent participation in other interventional clinical trials, participation in
other clinical trials less than 30 days before signing the ICF (provided the patient
has received at least one administration of experimental therapy), as well as
previous participation in this clinical trial (provided the patient has received at
least one administration of the drug RPH-075).
18. Acute infectious diseases or activation of chronic infectious diseases less than 28
days before the expected date of randomization into the study.
19. Active hepatitis B, hepatitis C, human immunodeficiency viruses (HIV) infection.
20. Therapy with live vaccines during the period 30 days before the expected date of
randomization into the study. For patients receiving therapy with approved
severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV2) vaccines,
instructions for use and/or local requirements should be followed. The use of the
Sputnik V vaccine is acceptable, provided that at least 7 days have passed from the
moment of administration of the second component of the vaccine to the first
administration of the study drug).
21. History of interstitial lung disease (non-infectious nature)/pneumonitis requiring
the use of steroid therapy, current pneumonitis/Interstitial lung disease (ILD).
22. Impossibility of intravenous administration of the study drug.
23. Impossibility of intravenous contrast.
24. Hypersensitivity (grade 3 or more) to any of the components of the drug
RPH-075/Keytruda®.
25. History of hypersensitivity to monoclonal antibody drugs.
26. Pregnancy or breastfeeding.
27. The presence of any other significant concomitant diseases or conditions that could,
in the reasonable opinion of the study physician, adversely affect the patient's
participation and well-being in the study and/or distort the evaluation of the study
results.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Federal State Budgetary Institution "National Medical Research Center of Radiology" of the Ministry of Health of the Russian Federation
Address:
City:
Obninsk
Zip:
249036
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution "Clinical Oncological Dispensary No. 1" of the Ministry of Health of the Krasnodar Territory
Address:
City:
Krasnodar
Zip:
350040
Country:
Russian Federation
Facility:
Name:
Regional Budgetary Healthcare Institution "Kursk Oncological Research and Clinical Center named after G.E. Ostroverkhov"
Address:
City:
Kislino
Zip:
305524
Country:
Russian Federation
Facility:
Name:
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"
Address:
City:
Istra
Zip:
143515
Country:
Russian Federation
Facility:
Name:
The State budgetary healthcare Institution of the Stavropol Territory "Pyatigorsk Interdistrict Oncological Dispensary"
Address:
City:
Pyatigorsk
Zip:
357502
Country:
Russian Federation
Facility:
Name:
The State Autonomous Healthcare Institution of the Sverdlovsk region "Sverdlovsk Regional Oncological Dispensary"
Address:
City:
Ekaterinburg
Zip:
620036
Country:
Russian Federation
Facility:
Name:
State Autonomous Healthcare Institution Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan
Address:
City:
Ufa
Zip:
450054
Country:
Russian Federation
Facility:
Name:
State Autonomous Healthcare Institution "Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z.Segal"
Address:
City:
Kazan
Zip:
420029
Country:
Russian Federation
Facility:
Name:
Budgetary Healthcare Institution of the Udmurt Republic "Sergey Grigoryevich Primushko Republican Clinical Oncological Dispensary of the Ministry of Health of the Udmurt Republic"
Address:
City:
Izhevsk
Zip:
426009
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution of the Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
Address:
City:
Arkhangelsk
Zip:
163045
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution "Regional Oncological Dispensary"
Address:
City:
Irkutsk
Zip:
664035
Country:
Russian Federation
Facility:
Name:
Regional budgetary healthcare institution "Ivanovo Regional Oncological Dispensary"
Address:
City:
Ivanovo
Zip:
153040
Country:
Russian Federation
Facility:
Name:
Kaluga Region State Budgetary Healthcare Institution "Kaluga Regional Clinical Oncological Dispensary"
Address:
City:
Kaluga
Zip:
248007
Country:
Russian Federation
Facility:
Name:
State Budgetary healthcare Institution "Kuzbass Clinical Oncological Dispensary named after M.S. Rappoport"
Address:
City:
Kemerovo
Zip:
650036
Country:
Russian Federation
Facility:
Name:
Regional State Budgetary Healthcare Institution "Krasnoyarsk Regional Clinical Oncological Dispensary named after A.I. Kryzhanovsky"
Address:
City:
Krasnoyarsk
Zip:
660133
Country:
Russian Federation
Facility:
Name:
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"
Address:
City:
Moscow
Zip:
108814
Country:
Russian Federation
Facility:
Name:
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation
Address:
City:
Moscow
Zip:
115478
Country:
Russian Federation
Facility:
Name:
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"
Address:
City:
Moscow
Zip:
117152
Country:
Russian Federation
Facility:
Name:
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)
Address:
City:
Moscow
Zip:
119991
Country:
Russian Federation
Facility:
Name:
Branch Office of "Hadassah Medical Ltd"
Address:
City:
Moscow
Zip:
121205
Country:
Russian Federation
Facility:
Name:
"Moscow Center for Rehabilitation Treatment" LLC
Address:
City:
Moscow
Zip:
121552
Country:
Russian Federation
Facility:
Name:
Medsi Group of Companies JSC
Address:
City:
Moscow
Zip:
123056
Country:
Russian Federation
Facility:
Name:
"Research lab" LLC
Address:
City:
Moscow
Zip:
127521
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution of the Nizhny Novgorod region "Nizhny Novgorod Regional Clinical Oncological Dispensary"
Address:
City:
Nizhny Novgorod
Zip:
603126
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution of the Novosibirsk region "Novosibirsk Regional Clinical Oncological Dispensary"
Address:
City:
Novosibirsk
Zip:
630108
Country:
Russian Federation
Facility:
Name:
Budgetary healthcare institution of the Omsk region "Clinical Oncological Dispensary"
Address:
City:
Omsk
Zip:
644013
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution of the Perm Territory "Perm Regional Oncological Dispensary"
Address:
City:
Perm
Zip:
614066
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital
Address:
City:
Saint Petersburg
Zip:
188300
Country:
Russian Federation
Facility:
Name:
Private healthcare institution "Clinical Hospital "Russian Railways-Medicine" of the city of St. Petersburg"
Address:
City:
Saint Petersburg
Zip:
195271
Country:
Russian Federation
Facility:
Name:
"Euro Cityclinic" LLC
Address:
City:
Saint Petersburg
Zip:
197022
Country:
Russian Federation
Facility:
Name:
St. Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
Address:
City:
Saint Petersburg
Zip:
197022
Country:
Russian Federation
Facility:
Name:
State Budgetary Healthcare Institution "Samara Regional Clinical Oncological Dispensary"
Address:
City:
Samara
Zip:
443031
Country:
Russian Federation
Facility:
Name:
State Healthcare Institution "Regional Clinical Oncological Dispensary"
Address:
City:
Saratov
Zip:
410053
Country:
Russian Federation
Facility:
Name:
Regional State Budgetary Healthcare Institution "Smolensk Regional Oncological Clinical Dispensary"
Address:
City:
Smolensk
Zip:
214000
Country:
Russian Federation
Facility:
Name:
Siberian State Medical University of the Ministry of Healthcare of Russian Federation
Address:
City:
Tomsk
Zip:
634050
Country:
Russian Federation
Facility:
Name:
The State Autonomous healthcare Institution of the Tyumen region "Multidisciplinary clinical Medical Center "Medical City"
Address:
City:
Tyumen
Zip:
625041
Country:
Russian Federation
Start date:
September 27, 2023
Completion date:
January 2026
Lead sponsor:
Agency:
R-Pharm
Agency class:
Industry
Collaborator:
Agency:
Data Management 365
Agency class:
Industry
Collaborator:
Agency:
Exacte Labs LLC
Agency class:
Other
Collaborator:
Agency:
Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor
Agency class:
Other
Source:
R-Pharm
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06320353