A Phase I Comparative Study of Pharmacokinetics, Safety, and Efficacy of RPH-002 and Erbitux® in Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma

An Open-label, Randomized, Multicenter Comparative Study of the Pharmacokinetics, Safety, and Efficacy of RPH-002 and Erbitux® in Patients With Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma

The primary objective of this clinical study is to compare the pharmacokinetic parameters of drugs RPH-002 and Erbitux® after a single intravenous administration, as well as to evaluate the safety of drug RPH-002 in comparison with drug Erbitux® when used in combination with Docetaxel and Cisplatin as first-line therapy in patients with Recurrent Head and Neck Squamous Cell Carcinoma. In addition, this study will include a comparative assessment of immunogenicity and a pilot evaluation of efficacy

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: RPH-002; Drug: cisplatin; Drug: docetaxel; Drug: Erbitux®

Detailed Description

This study is a multicenter, open-label, randomized Phase I study

This clinical study includes the following stages:

• Stage 1: Evaluation of the pharmacokinetics of drugs RPH-002 and Erbitux® after the first administration, and evaluation of the safety and immunogenicity of drugs RPH-002 and Erbitux® after four administrations of the study therapy
• Stage 2: Evaluation of pharmacokinetics, safety, immunogenicity, and pilot efficacy of drugs RPH-002 and Erbitux® during up to 18 weeks of therapy
• Stage 3: Evaluation of safety, immunogenicity, and pilot efficacy of RPH-002 and Erbitux® after 6 months of therapy, as well as evaluation of safety, immunogenicity, and pilot efficacy of drug RPH-002 after 1 year of therapy

Therapy with cetuximab within this clinical study will continue until disease progression or the development of unacceptable toxicity

Disease progression is defined as the presence of one or more of the following criteria:

• Clinical progression as assessed by the investigator
• Radiologically confirmed progression according to RECIST 1.1 criteria: an increase of at least 20% in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions

The maximum duration of therapy with cetuximab within the study will be 54 weeks

The study will include the following periods:

1. Screening Period 1 (up to 15 days)

   Includes Days -14 to 0 (prior to the first administration of the investigational product/comparator)

2. Main Period (Period 1)

   The main study period includes Days 1-126

   Patients will be randomized in a 1:1 ratio into one of two study groups: RPH-002 and Erbitux®. Patients will receive combination therapy with RPH-002 or Erbitux®, docetaxel, and cisplatin for 18 weeks, or until the development of unacceptable toxicity or disease progression

   The Main Period includes collection of data on complaints and symptoms, physical examination, assessment of vital signs (body temperature, blood pressure, pulse), monitoring of laboratory parameters (hematology, serum biochemistry, coagulation tests, blood analysis, and urinalysis), blood sampling for determination of serum cetuximab concentration and immunogenicity assessment, ECG, and evaluation of Karnofsky performance status. Tumor response assessment will be performed every 6 weeks during Period 1

3. Screening Period 2 (up to 8 days)

   Includes Days -7 to 0 (prior to Visit 1 of the Maintenance Therapy Period). During Screening Period 2, the patient's general condition and laboratory and instrumental test results will be evaluated to determine eligibility for continuation of therapy in the Maintenance Therapy Period

4. Maintenance Therapy Period (Period 2)

   Days 127-386

   Patients eligible for the Maintenance Therapy Period will be those who have achieved stable disease or an objective tumor response according to RECIST 1.1 at Week 18 of the Main Period

   During the Maintenance Therapy Period, patients will receive monotherapy with RPH-002 or Erbitux® at the same dose regimen (250 mg/m²) once weekly. The maximum number of administrations of cetuximab during this period will be 36

   Treatment during this period will continue until the earliest of the following:

   • 54 weeks from the start of study therapy;
   • Disease progression (according to RECIST 1.1 or clinical progression);
   • Development of unacceptable toxicity

   The Period includes collection of data on complaints and symptoms, physical examination, assessment of vital signs (body temperature, blood pressure, pulse), monitoring of laboratory parameters (hematology, serum biochemistry, coagulation tests, and urinalysis), collection of biological samples for immunogenicity analysis, ECG, and evaluation of Karnofsky performance status. Tumor response assessment will be performed every 6 weeks during Period 2

5. Follow-up Period

This study period includes safety evaluation of the investigational therapy in all patients who completed Period 1 and did not enter Period 2, as well as all patients who completed therapy during Period 2. The follow-up visit will be conducted 28 ± 3 days after the last administration of the study treatment

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russia
  • Barnaul, Russia, 656045
    • Regional State Budgetary Healthcare Institution "Altai Regional Oncological Dispensary"
  • Cheboksary, Russia, 428020
    • Autonomous Institution of the Chuvash Republic "Republican Clinical Oncological Dispensary" of the Ministry of Health of the Chuvash Republic
  • Irkutsk, Russia, 664035
    • State Budgetary Healthcare Institution "Regional Oncological Dispensary"
  • Istra, Russia, 143515
    • State Budgetary Healthcare Institution of Moscow "Moscow City Oncological Hospital No. 62, Department of Health of Moscow"
  • Ivanovo, Russia, 153040
    • Regional Budgetary Healthcare Institution "Ivanovo Regional Oncological Dispensary"
  • Kaluga, Russia, 248007
    • State Budgetary Healthcare Institution of Kaluga Region "Kaluga Regional Clinical Oncological Dispensary"
  • Kuz'molovskiy, Russia, 191104
    • State Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital"
  • Moscow, Russia, 129090
    • State Budgetary Healthcare Institution of Moscow "City Clinical Hospital named after S.S. Yudin, Department of Health of Moscow"
  • Moscow, Russia, 143442
    • Joint-Stock Company "Medsi Group of Companies"
  • Moscow, Russia, 119435
    • Federal State Autonomous Higher Education Institution "First Moscow State Medical University named after I.M. Sechenov" of the Ministry of Health of the Russian Federation (Sechenov University)
  • Moscow, Russia, 119602
    • Limited Liability Company "COMPAS-LA"
  • Novosibirsk, Russia, 630108
    • State Budgetary Healthcare Institution of Novosibirsk Region "Novosibirsk Regional Clinical Oncological Dispensary"
  • Obninsk, Russia, 249036
    • Federal State Budgetary Institution "National Medical Research Center of Radiology" of the Ministry of Health of the Russian Federation, Branch: A.F. Tsyba Medical Radiological Research Center
  • Omsk, Russia, 644013
    • Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
  • Pushkin, Russia, 196603
    • Private Medical Institution "Euromedservice"
  • Saint Petersburg, Russia, 197022
    • Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
  • Ufa, Russia, 450054
    • State Autonomous Healthcare Institution "Republican Clinical Oncological Dispensary" of the Ministry of Health of the Republic of Bashkortostan
  • Yaroslavl, Russia, 150054
    • State Budgetary Healthcare Institution of Yaroslavl Region "Regional Clinical Oncological Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Main Period (Period 1)

1. A voluntarily signed and dated Informed Consent form (ICF) of the patient
2. Histologically confirmed squamous cell carcinoma of the head and neck
3. Body mass index (BMI) between 18 and 30 kg/m^2, inclusive
4. Documented unresectable locoregional recurrence or distant metastases, or progression after prior chemoradiotherapy or combination therapy completed >3 months before screening, not amenable to local treatment (except cases with high risk of tumor lysis or bleeding), or newly diagnosed metastatic disease not previously treated with systemic therapy. Study treatment is first-line therapy
5. At least one measurable lesion per RECIST 1.1
6. Karnofsky performance status ≥70%

7. Screening laboratory values within the following limits (per local lab normal ranges):

   • Hemoglobin ≥90 g/L
   • Leukocytes ≥3.0 × 10^9/L
   • Neutrophils ≥1.5 × 10^9/L
   • Platelets ≥100 × 10^9/L
   • Total bilirubin ≤2 × Upper Limit of Normal (ULN)
   • Aspartate aminotransferase (AST) ≤3 × ULN
   • Alanine aminotransferase (ALT) ≤3 × ULN
   • Estimated glomerular filtration rate (eGFR) ≥60 mL/min
8. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
9. Ability and willingness to comply with study protocol and procedures for the planned duration of participation
10. Ability to undergo required pharmacokinetic sample collection, as judged by the investigator

Maintenance Therapy Period (Period 2)

1. Documented tumor response or disease stabilization per RECIST 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) at Week 18 of the Main Period
2. Ability and willingness to provide written informed consent for participation in Period 2
3. Karnofsky performance status ≥ 70%

4. Laboratory values within the following limits (per local lab normal ranges):

   • Hemoglobin ≥ 90 g/L
   • Leukocytes ≥ 3.0 × 10^9/L
   • Neutrophils ≥ 1.5 × 10^9/L
   • Platelets ≥ 100 × 10^9/L
   • Total bilirubin ≤ 2 × ULN (upper limit of normal)
   • AST ≤ 3 × ULN
   • ALT ≤ 3 × ULN
   • eGFR ≥ 60 mL/min
5. Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt

Exclusion Criteria:

Main Period (Period 1)

1. Prior therapy with cetuximab or other monoclonal antibody-based biologics
2. Chemotherapy, radiotherapy, or surgery for head and neck cancer within 3 months before screening
3. Any other surgery (except biopsy, implantable venous port placement, or urgent non-cancer surgery) within 3 months before screening
4. Nasopharyngeal carcinoma
5. Other malignancy within the past 5 years or prior/concurrent squamous cell carcinoma (except cured in situ ductal carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer)
6. Expected survival < 3 months
7. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
8. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
9. Active infection requiring systemic antibiotic therapy
10. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol within 6 months prior to screening or during the study
11. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
12. Positive screening for HBsAg, anti-HCV, anti-HIV1/2 antibodies, or syphilis within 3 months prior to screening
13. Conditions preventing compliance with the study protocol per investigator
14. Participation in another investigational drug study within 6 months prior to screening
15. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
16. Known hypersensitivity to any component of study therapy or combination chemotherapy drugs
17. Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits

Maintenance Therapy Period (Period 2)

1. No documented tumor response or disease stabilization per RECIST 1.1 by CT or MRI at Week 18 of the Main Period
2. Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
3. Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
4. Active infection requiring systemic antibiotics
5. Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol for Period 2
6. Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
7. Conditions preventing compliance with study procedures per investigator
8. Participation in another investigational drug study
9. Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
10. Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RPH-002 + docetaxel + cisplatin; Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity	Drug: RPH-002; RPH-002: solution for infusion, 5 mg/mL RPH-002 is administered IV once weekly. The first dose is 400 mg/m², given as a 20 mg/m² IV test dose over 10 minutes followed by 380 mg/m² IV over the remainder of 120 minutes. Subsequent weekly doses are 250 mg/m² IV over 60 minutes Thirty to sixty minutes prior to the infusion of RPH-002, premedication with diphenhydramine 50 mg (or other H1-receptor antagonist) administered orally or intravenously and a glucocorticosteroid (e.g., dexamethasone 8 mg) is required; Other Names: cetuximab; Drug: cisplatin; Solution for injection (500 μg / 1 mg / 1 mL; 10 / 25 / 50 / 100 mg per vial) Cisplatin is administered intravenously at 75 mg/m² once every 3 weeks. Hydration is required to promote diuresis and reduce cisplatin-related nephrotoxicity; Drug: docetaxel; Concentrate for solution for infusion (40 mg/mL; 0.5 mL / 2 mL per vial) Docetaxel is administered intravenously at 75 mg/m² over 60 minutes once every 3 weeks, prior to the cisplatin infusion and concurrently with prehydration
Active Comparator: Erbitux® + docetaxel + cisplatin; Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity	Drug: cisplatin; Solution for injection (500 μg / 1 mg / 1 mL; 10 / 25 / 50 / 100 mg per vial) Cisplatin is administered intravenously at 75 mg/m² once every 3 weeks. Hydration is required to promote diuresis and reduce cisplatin-related nephrotoxicity; Drug: docetaxel; Concentrate for solution for infusion (40 mg/mL; 0.5 mL / 2 mL per vial) Docetaxel is administered intravenously at 75 mg/m² over 60 minutes once every 3 weeks, prior to the cisplatin infusion and concurrently with prehydration; Drug: Erbitux®; Erbitux®: solution for infusion, 5 mg/mL Erbitux® is administered IV once weekly. The first dose is 400 mg/m², given as a 20 mg/m² IV test dose over 10 minutes followed by 380 mg/m² IV over the remainder of 120 minutes. Subsequent weekly doses are 250 mg/m² IV over 60 minutes Thirty to sixty minutes prior to the infusion of Erbitux®, premedication with diphenhydramine 50 mg (or other H1-receptor antagonist) administered orally or intravenously and a glucocorticosteroid (e.g., dexamethasone 8 mg) is required; Other Names: cetuximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients (%) with adverse drug reactions (ADRs) of any severity	Proportion of patients (%) with adverse drug reactions (ADRs) of any severity	Up to Day 365
Area under the pharmacokinetic curve "concentration-time" (AUC(0-168)) of cetuximab	Area under the pharmacokinetic curve "concentration-time" of cetuximab after the first (single dose) administration, truncated at the point before the second administration, i.e. up to 168 hours	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients (%) with adverse events (AEs) of any severity	Proportion of patients (%) with adverse events (AEs) of any severity	Up to Day 365
Proportion of patients (%) with AEs of severity grade ≥ 3	Proportion of patients (%) with AEs of severity grade ≥ 3 according to CTCAE 5.0	Up to Day 365
Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab	Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab	Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36
Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab	Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab	Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36
Maximum serum concentration of cetuximab after the first administration (Cmax)	Maximum serum concentration of cetuximab after the first administration (Cmax)	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Maximum serum concentration of cetuximab at steady state (Cmax ss)	Maximum serum concentration of cetuximab at steady state (Cmax ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Minimum serum concentration of cetuximab at steady state (Cmin ss)	Minimum serum concentration of cetuximab at steady state (Cmin ss)	Within 30 ± 10 minutes prior to dosing at Visits 3 (Day 15), 5 (Day 29), 6 (Day 36), 7 (Day 43), 8 (Day 50), 9 (Day 57), 12 (Day 78), 15 (Day 99), and 18 (Day 120)
Area under the pharmacokinetic curve "concentration-time" of cetuximab at steady state (AUC tau)	Area under the pharmacokinetic curve "concentration-time" of cetuximab at steady state (AUC tau ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Proportion of patients (%) with serious adverse events (SAEs)	Proportion of patients (%) with SAEs	Up to Day 365
Proportion of patients (%) with serious adverse drug reactions (SADRs)	Proportion of patients (%) with SADRs	Up to Day 365
Proportion of patients (%) with ADRs of severity grade ≥ 3	Proportion of patients (%) with ADRs of severity grade ≥ 3	Up to Day 365
Proportion of patients (%) who required discontinuation of treatment due to development of ADRs	Proportion of patients (%) who required discontinuation of treatment due to development of ADRs	Up to Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) expressed as the rate (%) of 6-month PFS PFS is defined as the time from randomization to disease progression according to RECIST 1.1 (an increase of at least 20% in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions), clinical progression, or death from any cause	Up to Week 9 (Visit 9) in Period 2
Progression-free survival (PFS) (non-comparative evaluation in the RPH-002 group)	Progression-free survival (PFS) expressed as the rate (%) of 1-year PFS (non-comparative evaluation in the RPH-002 group) PFS is defined as the time from randomization to disease progression according to RECIST 1.1 (an increase of at least 20% in the sum of diameters of target lesions compared with the smallest sum recorded during the study (with an absolute increase of at least 5 mm), or the appearance of one or more new lesions), clinical progression, or death from any cause	Up to Day 365
Overall survival (OS) (non-comparative evaluation in the RPH-002 group)	Overall survival (OS) expressed as median OS for a period of up to 1 year of therapy (non-comparative evaluation in the RPH-002 group)	Up to Day 365
Area under the pharmacokinetic curve "concentration-time" (AUC(0-∞)) of cetuximab	Area under the pharmacokinetic curve "concentration-time" of cetuximab after the first administration to infinity (AUC(0-∞))	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Time to reach the maximum concentration of cetuximab in the blood serum after the first administration (Tmax)	Time to reach the maximum concentration of cetuximab in the blood serum after the first administration (Tmax)	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Elimination half-life of cetuximab after the first administration (T1/2)	Elimination half-life of cetuximab after the first administration (T1/2)	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Volume of distribution of cetuximab after the first administration (Vd)	Volume of distribution of cetuximab after the first administration (Vd)	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Elimination rate constant of cetuximab after the first administration (Kel)	Elimination rate constant of cetuximab after the first administration (Kel)	Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Area under the pharmacokinetic curve "concentration-time" of cetuximab to infinity at steady state (AUC(0-∞) ss)	Area under the pharmacokinetic curve "concentration-time" of cetuximab to infinity at steady state (AUC(0-∞) ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Time to reach the maximum concentration of cetuximab at steady state (Tmax ss)	Time to reach the maximum concentration of cetuximab at steady state (Tmax ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Elimination half-life of cetuximab at steady state (T1/2 ss)	Elimination half-life of cetuximab at steady state (T1/2 ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Volume of distribution of cetuximab at steady state (Vd, ss)	Volume of distribution of cetuximab at steady state (Vd, ss)	Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose
Residual concentration of cetuximab at repeated administration (Cthrough)	Residual concentration of cetuximab at repeated administration (Cthrough)	Visits 18 (Day 120)
Objective response rate (%) (ORR)	Objective response rate (%) (ORR) for a period of up to 18 weeks of therapy inclusive The objective response rate (ORR) is defined as the percentage of patients in each treatment group who achieve a complete or partial tumor response to therapy according to RECIST 1.1 criteria: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks compared with the baseline sum at screening	At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120)
Objective response rate (%) (ORR)	Objective response rate (%) (ORR) for a period of up to 6 months of therapy inclusive The objective response rate (ORR) is defined as the percentage of patients in each treatment group who achieve a complete or partial tumor response to therapy according to RECIST 1.1 criteria: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks compared with the baseline sum at screening	Up to Week 9 (Visit 9) in Period 2
Disease control rate (DCR) (%)	Disease control rate (DCR) (%) for a period of up to 18 weeks of therapy inclusive The disease control rate is defined as the percentage of patients in a given treatment group who achieve a complete response, partial response, or stable disease during therapy, in accordance with RECIST 1.1 criteria: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study	At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120)
Disease control rate (DCR) (%)	Disease control rate (DCR) (%) for a period of up to 6 months of therapy inclusive The disease control rate is defined as the percentage of patients in a given treatment group who achieve a complete response, partial response, or stable disease during therapy, in accordance with RECIST 1.1 criteria: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study	Up to Week 9 (Visit 9) in Period 2
Disease control rate (DCR) (%) (non-comparative evaluation in the RPH-002 group)	Disease control (DCR) (%) within a period of up to 1 year of therapy inclusive (non-comparative evaluation in the RPH-002 group) The disease control rate is defined as the percentage of patients in a given treatment group who achieve a complete response, partial response, or stable disease during therapy, in accordance with RECIST 1.1 criteria: Complete Response (CR) - disappearance of all target lesions, confirmed by CT scans for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be <10 mm; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions, maintained for at least 4 weeks compared with baseline (screening) measurements; Stable Disease (SD) - neither sufficient shrinkage in the sum of diameters to qualify as partial response nor sufficient increase to qualify as progressive disease compared with the smallest sum recorded during the study	At Visits 6, 12, and 18 in Period 1 (Days 36, 78, and 120) and Visits 6, 12, 18, 24, 30, and 36 in Period 2 (Weeks 6-36)
Objective response rate (%) (ORR) (non-comparative evaluation in the RPH-002 group)	Objective response rate (%) (ORR) for a period of up to 1 year of therapy inclusive (non-comparative evaluation in the RPH-002 group) The objective response rate (ORR) is defined as the percentage of patients in each treatment group who achieve a complete or partial tumor response to therapy according to RECIST 1.1 criteria: Complete response (CR): disappearance of all target lesions confirmed by CT for at least 4 weeks; the short axis of any lymph node previously considered pathological (target or non-target) must be < 10 mm; Partial response (PR): at least a 30% decrease in the sum of diameters of target lesions sustained for at least 4 weeks compared with the baseline sum at screening	At Visits 6, 12, and 18 in Period 1 (Days 36, 78, and 120) and Visits 6, 12, 18, 24, 30, and 36 in Period 2 (Weeks 6-36)

Collaborators and Investigators

• Sponsor: R-Pharm
• Investigators: Study Director: Mikhail Samsonov, R-Pharm

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2020
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): July 17, 2024

Study Registration Dates

• First Submitted: February 20, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Head and Neck Squamous Cell Carcinoma; RPH-002
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Docetaxel; Cetuximab; Cisplatin
• Other Study ID Numbers: CL01002062

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No