Study Comparing the Pharmacokinetics, Safety, and Efficacy of RPH-075 and Keytruda® in Patients With Malignant Neoplasms

NCT06307093 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: CL01860198
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 23

Brief 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 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.

Conditions

Skin Melanoma; Squamous Non-small-cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

cancer; melanoma; carcinoma; lung cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  Days: 1 - 22

Secondary Outcomes (13)

• Maximum Plasma Concentration (Cmax) of pembrolizumab

  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)

  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)

  pre-dose on days: 43, 64, 85, 148

• Area under the curve "concentration-time" of pembrolizumab at steady state (AUCtau ss)

  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)

  Days: 1 - 168

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

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); 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);
• 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).

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 "NMIC of Hematology" of the Ministry of Health of the Russian Federation: collaborator
• Federal State Budgetary Institution of the Central Research Institute of Epidemiology of Rospotrebnadzor: collaborator

Study Sites (23)

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, Russia

Location

"New Clinic" LLC

Pyatigorsk, Stavropol Territory, 357500, Russia

Location

Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"

Barnaul, The Altai Republic, 656045, Russia

Location

Autonomous Institution of the Chuvash Republic "Republican Clinical Oncological Dispensary" of the Ministry of Health of the Chuvash Republic

Cheboksary, The Chuvash Republic, 428020, 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 Budgetary Healthcare Institution of the Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary"

Arkhangelsk, 163045, Russia

Location

Regional budgetary healthcare institution "Ivanovo Regional Oncological Dispensary"

Ivanovo, 153040, Russia

Location

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

Kemerovo, 650036, 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, 105005, Russia

Location

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, 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

Federal State Budgetary Scientific Institution "Russian Scientific Center of Surgery named after Academician B.V. Petrovsky"

Moscow, 119435, Russia

Location

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, Russia

Location

Medsi Group of Companies JSC

Moscow, 123056, Russia

Location

"Research lab" LLC

Moscow, 127521, 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

"Av Medical Group" LLC

Saint Petersburg, 196006, Russia

Location

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

Saint Petersburg, 197022, Russia

Location

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, Russia

Location

State Budgetary Healthcare Institution "Samara Regional Clinical Oncological Dispensary"

Samara, 443031, 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; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Carcinoma; Lung 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; Carcinoma, Squamous Cell; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Mikhail Samsonov

  R-Pharm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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 5, 2024
• First Posted: March 12, 2024
• Study Start: March 1, 2023
• Primary Completion: December 11, 2023
• Study Completion: July 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

RU (23)