Skin MelanomaPhase 1NCT06307093
Study Comparing the Pharmacokinetics, Safety, and Efficacy of RPH-075 and Keytruda® in Patients With Malignant Neoplasms
A Phase 1 study testing RPH-075 and Keytruda® in people with Skin Melanoma and Squamous Non-small-cell Lung Cancer, run by R-Pharm at 23 sites in Russia.
Trial summary
The goal of this double-blind, randomized study is to establish the equivalence of pharmacokinetic properties, as well as the comparability of safety, immunogenicity and pharmacodynamics of the drug RPH-075 (international nonproprietary name (INN) is pembrolizumab) in comparison with the drug Keytruda® (INN is… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Skin Melanoma, Squamous Non-small-cell Lung Cancer, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- RPH-075 and Keytruda®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 23 sitesRussia
- Study dates
- 1 Mar 2023to 28 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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); squamous non-small cell lung cancer with Programmed death-ligand 1 (PD-L1) expression level ≥ 1% of tumor cells; head and neck squamous cell carcinoma with PD-L1 Tumor Proportion Score (TPS) expression level ≥ 50%.
- 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);
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- 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);
- with squamous non-small-cell lung cancer:
- newly identified unresectable (stage III) or metastatic (stage IV) with PD-L1 expression level ≥ 1%, with intolerance to 1st line chemotherapy (the drug will be used as 1st line therapy);
- unresectable (stage III) or metastatic (stage IV) with PD-L1 expression level ≥ 1 %, with progression against the background of 1st line antitumor therapy (the drug will be used as a 2nd line therapy);
- head and neck squamous cell carcinoma: • unresectable (stage III) or metastatic (stage IV) with PD-L1 TPS expression level ≥ 50% with progression during or after platinum-containing chemotherapy of the 1st line (the drug will be used as a therapy of the 2nd line).
- 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).
- Body weight: 50 to 100 kg.
- 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).
Who cannot join
- 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;
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- 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,
- hemoglobin < 90 g/L.
- Renal dysfunction:
- creatinine > 1.5 × Upper limit of normal (ULN) or glomerular filtration rate < 45 ml/min.
- 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
- Conducting surgical treatment less than 28 days, radiation therapy less than 14 days before the expected date of randomization into the study.
- Uveal melanoma or melanoma of the mucous membranes.
- Possibility of radical removal of all metastatic foci.
- 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)
- Previous therapy with pembrolizumab and other anti- Programmed cell death 1 (PD-1)/PD-L1/Programmed Cell Death 1 Ligand 2 (PD-L2) drugs.
- 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 carcinoma of the skin.
- 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.).
- 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).
- Acute infectious diseases or activation of chronic infectious diseases less than 28 days before the expected date of randomization into the study.
- Active hepatitis B, hepatitis C, human immunodeficiency viruses (HIV) infection.
- 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).
- History of interstitial lung disease (non-infectious nature)/pneumonitis requiring the use of steroid therapy, current pneumonitis/Interstitial lung disease (ILD).
- Impossibility of intravenous administration of the study drug.
- Impossibility of intravenous contrast.
- Hypersensitivity (grade 3 or more) to any of the components of the drug RPH-075/Keytruda®.
- History of hypersensitivity to monoclonal antibody drugs.
- Pregnancy or breastfeeding.
- 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.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Russia23 sites
State Budgetary Healthcare Institution of the Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"
Arkhangelsk, 163045
Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"
Barnaul, The Altai Republic, 656045
Autonomous Institution of the Chuvash Republic "Republican Clinical Oncological Dispensary" of the Ministry of Health of the Chuvash Republic
Cheboksary, The Chuvash Republic, 428020
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, 143423
Regional budgetary healthcare institution "Ivanovo Regional Oncological Dispensary"
Ivanovo, 153040
State Budgetary healthcare Institution "Kuzbass Clinical Oncological Dispensary named after M.S. Rappoport"
Kemerovo, 650036
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, 105005
State Budgetary Institution of Healthcare of the city of Moscow "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of the Department of Healthcare of the City of Moscow"
Moscow, 111123
Federal State Budgetary Institution "N.N. Blokhin National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation
Moscow, 115478
Federal State Budgetary Scientific Institution "Russian Scientific Center of Surgery named after Academician B.V. Petrovsky"
Moscow, 119435
Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
Moscow, 119991
Medsi Group of Companies JSC
Moscow, 123056
"Research lab" LLC
Moscow, 127521
State Budgetary Healthcare Institution of the Perm Territory "Perm Regional Oncological Dispensary"
Perm, 614066
"New Clinic" LLC
Pyatigorsk, Stavropol Territory, 357500
State Budgetary Healthcare Institution Leningrad Regional Clinical Hospital
Saint Petersburg, 188300
Private healthcare institution "Clinical Hospital "Russian Railways-Medicine" of the city of St. Petersburg"
Saint Petersburg, 195271
"Av Medical Group" LLC
Saint Petersburg, 196006
St. Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
Saint Petersburg, 197022
Federal State Budgetary Institution "N.N. Petrov National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation
Saint Petersburg, 197758
State Budgetary Healthcare Institution "Samara Regional Clinical Oncological Dispensary"
Samara, 443031
The State Autonomous healthcare Institution of the Tyumen region "Multidisciplinary clinical Medical Center "Medical City"
Tyumen, 625041
State Autonomous Healthcare Institution Republican Clinical Oncological Dispensary of the Ministry of Health of the Republic of Bashkortostan
Ufa, The Republic of Bashkortostan, 450054
About this study
Official title: International, Multicenter, Double-blind, Randomized, Comparative Study of the Pharmacokinetics, Safety and Efficacy of RPH-075 and Keytruda® in Patients With Malignant Neoplasms
The goal of this double-blind, randomized study is to establish the equivalence of pharmacokinetic properties, as well as the comparability of safety, immunogenicity and pharmacodynamics of the drug RPH-075 (international nonproprietary name (INN) is pembrolizumab) in comparison with the drug Keytruda® (INN is pembrolizumab) after a single intravenous injection to patients with malignant neoplasms as a first or second line therapy in a monotherapy regimen.
The main main tasks are:
Read more
- To evaluate and compare the pharmacokinetic properties of RPH-075 and Keytruda® after a single intravenous administration of pembrolizumab to patients with malignant neoplasms;
- To evaluate the safety profile of the drug RPH-075 in comparison with the drug Keytruda® when used in patients with malignant neoplasms when used as a 1st or 2nd line therapy in a monotherapy regimen.
This study will also include a comparative assessment of immunogenicity, pharmacodynamic parameters and a pilot evaluation of RPH-075 efficacy.
Read the detailed description
This study will include the following periods:
- Screening period (before 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.
- 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). In case of significant adverse events (AEs), pembrolizumab therapy may be postponed for up to 12 weeks. Therapy within the Main Study period will continue until (whichever comes first):
- 24 weeks (8 cycles);
- 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.
- 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.
- 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.
- 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).
- Being tested
- RPH-075, Keytruda®
- Keywords
- cancer, melanoma, carcinoma, lung cancer
- Medical subject headings
- Melanoma, Squamous Cell Carcinoma of Head and Neck, Neoplasms, Carcinoma, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RPH-075Drug
Also called pembrolizumab
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.)
Keytruda®Drug
Also called pembrolizumab
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.)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Keytruda® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the curve "concentration-time" (AUC(0-504)) of pembrolizumab
The area under the pharmacokinetic curve "concentration-time" of pembrolizumab after the first (single) administration, truncated to the second administration, i.e. the point 504 hours in both treatment groups.
Measured: pre-dose on Day 1 and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Incidence of Adverse Reactions (ARs)
Incidence of ARs in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 22
Secondary outcomes (13)
Maximum Plasma Concentration (Cmax) of pembrolizumab
Pembrolizumab Cmax after the first administration in both treatment groups.
Measured: pre-dose on Day 1 and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Maximum serum concentration of pembrolizumab at steady state (Сmax ss)
Pembrolizumab C(max ss) after 6th administration in both treatment groups.
Measured: pre-dose on Day 106 (6th administration) and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Minimal serum concentration of pembrolizumab at steady state (Сmin ss)
Pembrolizumab C(min ss) after 6th administration in both treatment groups.
Measured: pre-dose on days: 43, 64, 85, 148
Area under the curve "concentration-time" of pembrolizumab at steady state (AUCtau ss)
Area under the pharmacokinetic curve "concentration-time" of pembrolizumab at steady state (AUCtau ss) after 6th administration in both treatment groups.
Measured: pre-dose on Day 106 (6th administration) and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Incidence of Treatment-Emergent Adverse Events (AEs)
Incidence of treatment-emergent AEs in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 168
Incidence of Immune-mediated adverse reactions (imARs)
Incidence of imARs in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 168
Incidence of Treatment-Emergent AEs with grade 3 or more
Incidence of Treatment-Emergent AEs with grade 3 or more in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 743 (up to 28 days after last pembrolizumab administration)
Incidence of Treatment-Emergent ARs with grade 3 or more
Incidence of Treatment-Emergent ARs with grade 3 or more in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 168
Incidence of imARs with grade 3 or more
Incidence of imARs with grade 3 or more in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 168
Incidence of serious adverse events (SAEs)
Incidence of SAEs in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 743 (up to 28 days after last pembrolizumab administration)
Incidence of serious adverse reactions (SARs)
Incidence of SARs in both treatment groups by system Organ Class or Preferred Term
Measured: Days: 1 - 168
The proportion of patients (%) who required therapy discontinuation due to AR development
Measured: Days: 1 - 715
The proportion of patients (%) who developed binding antibodies and neutralizing antibodies to pembrolizumab
Measured: Days: 1, 22, 64, 106, 148
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2024
- Study start1 Mar 2023
- Primary completion15 Jul 2023
- Study completion28 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Skin MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- R-Pharm
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Data Management 365, Exacte Labs LLC, Federal State Budgetary Institution "NMIC of Hematology" of the Ministry of Health of the Russian Federation, Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor
- Responsible party
- Sponsor
- Investigators
- Mikhail Samsonov, Study director, R-Pharm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06307093
- Sponsor's protocol ID
- CL01860198
- Status last verified
- Jul 2026
- First submitted
- 5 Mar 2024
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International, Multicenter, Double-blind, Randomized, Comparative Study of the Pharmacokinetics, Safety and Efficacy of RPH-075 and Keytruda® in Patients With Malignant Neoplasms
- ClinicalTrials.gov ID
- NCT06307093
- Acronym / sponsor ID
- CL01860198
- Keywords
- cancer, melanoma, carcinoma, lung cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- R-PharmIndustry (pharma, biotech, devices)
- Collaborators
- Data Management 365, Exacte Labs LLC, Federal State Budgetary Institution "NMIC of Hematology" of the Ministry of Health of the Russian Federation, Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 15 Jul 2023 (actual)
- Study completion
- 28 Jul 2025 (actual)
- First posted
- 12 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this double-blind, randomized study is to establish the equivalence of pharmacokinetic properties, as well as the comparability of safety, immunogenicity and pharmacodynamics of the drug RPH-075 (international nonproprietary name (INN) is pembrolizumab) in comparison with the drug Keytruda® (INN is pembrolizumab) after a single intravenous injection to patients with malignant neoplasms as a first or second line therapy in a monotherapy regimen.
The main main tasks are:
- To evaluate and compare the pharmacokinetic properties of RPH-075 and Keytruda® after a single intravenous administration of pembrolizumab to patients with malignant neoplasms;
- To evaluate the safety profile of the drug RPH-075 in comparison with the drug Keytruda® when used in patients with malignant neoplasms when used as a 1st or 2nd line therapy in a monotherapy regimen.
This study will also include a comparative assessment of immunogenicity, pharmacodynamic parameters and a pilot evaluation of RPH-075 efficacy.
Detailed description
This study will include the following periods:
- Screening period (before 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.
- 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). In case of significant adverse events (AEs), pembrolizumab therapy may be postponed for up to 12 weeks. Therapy within the Main Study period will continue until (whichever comes first):
- 24 weeks (8 cycles);
- 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.
- 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.
- 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.
- 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RPH-075 | Experimental | Drug: RPH-075Pembrolizumab 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. |
| Keytruda® | Active comparator | Drug: Keytruda®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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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); squamous non-small cell lung cancer with Programmed death-ligand 1 (PD-L1) expression level ≥ 1% of tumor cells; head and neck squamous cell carcinoma with PD-L1 Tumor Proportion Score (TPS) expression level ≥ 50%.
- The following patient populations:
- 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.
Key exclusion criteria (40 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RPH-075Also: pembrolizumab100 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.) | Drug | RPH-075 |
| Keytruda®Also: pembrolizumab100 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.) | Drug | Keytruda® |
Primary outcome
Area under the curve "concentration-time" (AUC(0-504)) of pembrolizumab
Time frame: pre-dose on Day 1 and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
The area under the pharmacokinetic curve "concentration-time" of pembrolizumab after the first (single) administration, truncated to the second administration, i.e. the point 504 hours in both treatment groups.
Incidence of Adverse Reactions (ARs)
Time frame: Days: 1 - 22
Incidence of ARs in both treatment groups by system Organ Class or Preferred Term
13 secondary outcomes
Maximum Plasma Concentration (Cmax) of pembrolizumab
Time frame: pre-dose on Day 1 and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Maximum serum concentration of pembrolizumab at steady state (Сmax ss)
Time frame: pre-dose on Day 106 (6th administration) and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Minimal serum concentration of pembrolizumab at steady state (Сmin ss)
Time frame: pre-dose on days: 43, 64, 85, 148
Area under the curve "concentration-time" of pembrolizumab at steady state (AUCtau ss)
Time frame: pre-dose on Day 106 (6th administration) and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose
Incidence of Treatment-Emergent Adverse Events (AEs)
Time frame: Days: 1 - 168
Incidence of Immune-mediated adverse reactions (imARs)
Time frame: Days: 1 - 168
Incidence of Treatment-Emergent AEs with grade 3 or more
Time frame: Days: 1 - 743 (up to 28 days after last pembrolizumab administration)
Incidence of Treatment-Emergent ARs with grade 3 or more
Time frame: Days: 1 - 168
Incidence of imARs with grade 3 or more
Time frame: Days: 1 - 168
Incidence of serious adverse events (SAEs)
Time frame: Days: 1 - 743 (up to 28 days after last pembrolizumab administration)
Incidence of serious adverse reactions (SARs)
Time frame: Days: 1 - 168
The proportion of patients (%) who required therapy discontinuation due to AR development
Time frame: Days: 1 - 715
The proportion of patients (%) who developed binding antibodies and neutralizing antibodies to pembrolizumab
Time frame: Days: 1, 22, 64, 106, 148
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikhail Samsonov study director
R-Pharm
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RPH-075 and Keytruda® in people with Skin Melanoma and Squamous Non-small-cell Lung Cancer, run by R-Pharm at 23 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the curve "concentration-time" (AUC(0-504)) of pembrolizumab (time frame: pre-dose on Day 1 and 0, 2, 4, 5, 6, 8, 12, 24, 48, 72, 120, 168, 336, 504 hours post-dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.