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

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

The primary objective of the study is to evaluate the comparability of efficacy, safety, and immunogenicity of RPH-002 and Erbitux® when administered in combination with docetaxel and cisplatin as first-line therapy in patients with advanced head and neck squamous cell carcinoma

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: RPH-002; Drug: Cisplatin; Drug: Docetaxel; Drug: Erbitux®

Detailed Description

This study is a international, multicenter, open-label, randomized, parallel-group Phase III study

The study will include the following periods:

1. Screening Period 1

   Includes Days -14 to -1 (prior to the first administration of the investigational product/comparator)

2. Main Period (Period 1)

   The main study period includes Days 1-126

   The Main Period begins with administration of cetuximab (RPH-002 or Erbitux®) and chemotherapy on Day 1 of Cycle 1. Chemotherapy continues for up to 6 cycles, each lasting 3 weeks (21 days). Chemotherapy agents are administered no earlier than 1 hour after completion of cetuximab infusion. Cetuximab is administered weekly for up to 18 doses

   In Period 1, tumor response is assessed every 6 weeks

3. Screening Period 2

   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 are evaluated to determine eligibility for continuation of therapy in the Maintenance Therapy Period

4. Maintenance Therapy Period (Period 2)

   Includes Days 127-386

   In the Maintenance Therapy Period, patients with a tumor response or stable disease at Week 18 of Period 1 are included in the study. Tumor response is assessed according to 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
   • Progressive Disease (PD) - at least a 20% increase 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
   • 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

   During the Maintenance Therapy Period, patients receive monotherapy with cetuximab at 250 mg/m² once weekly. The maximum number of administrations of cetuximab during this period is 36

   Therapy continues until the earliest of the following:

   • up to 54 weeks from the start of study treatment
   • disease progression (per RECIST 1.1 or clinical progression)
   • unacceptable toxicity

   Radiologically confirmed progression according to RECIST 1.1 criteria is defined as 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

   In Period 2, tumor response is assessed every 6 weeks

5. Follow-up Period

The Follow-Up Period assesses the safety of study therapy in all patients who complete Period 1 and do not enter Period 2, as well as in patients who complete therapy in Period 2. The period lasts 28 ± 3 days after the last study drug administration (if therapy completes as planned at 54 weeks) or until death, loss to follow-up, or Day 365, whichever occurs first. A single follow-up visit is conducted 28 ± 3 days after the last study drug administration

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russia
  • Arkhangelsk, Russia, 163045
    • State Budgetary Healthcare Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncological Dispensary"
  • 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"
  • Izhevsk, Russia, 571207
    • Budgetary Healthcare Institution of the Udmurt Republic "Sergey Grigoryevich Primushko Republican Clinical Oncological Dispensary" of the Ministry of Health of the Udmurt Republic
  • Kaluga, Russia, 248007
    • State Budgetary Healthcare Institution of Kaluga Region "Kaluga Regional Clinical Oncology Dispensary"
  • Kazan', Russia, 420029
    • State Autonomous Healthcare Institution "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan named after Professor M.Z. Sigal"
  • Kemerovo, Russia, 650036
    • State Budgetary Healthcare Institution "Kuzbass Clinical Oncology Dispensary named after M.S. Rappoport" (SBHI "KCOD")
  • Kirov, Russia, 610045
    • Kirov Regional State Clinical Budgetary Healthcare Institution "Center of Oncology and Medical Radiology"
  • Krasnodar, Russia, 350040
    • State Budgetary Healthcare Institution "Clinical Oncological Dispensary No. 1" of the Ministry of Health of Krasnodar Krai
  • Kuz'molovskiy, Russia, 191104
    • State Budgetary Healthcare Institution "Leningrad Regional Clinical Hospital"
  • Moscow, Russia, 119435
    • Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after I.M. Sechenov of the Ministry of Health of the Russian Federation (Sechenov University)
  • Moscow, Russia, 121205
    • Branch of the Limited Liability Company "Hadassah Medical Ltd." (LLC Branch "Hadassah Medical")
  • Moscow, Russia, 125367
    • Federal State Autonomous Institution "National Medical Research Center 'Medical and Rehabilitation Center'" of the Ministry of Health of the Russian Federation
  • Moscow, Russia, 105094
    • Federal State Budgetary Institution "N.N. Burdenko Main Military Clinical Hospital" of the Ministry of Defense of the Russian Federation
  • Moscow, Russia, 111123
    • State Budgetary Healthcare Institution of Moscow "A.S. Loginov Moscow Clinical Scientific and Practical Center" of the Moscow Department of Health
  • 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"
  • Nizhny Novgorod, Russia, 603081
    • State Autonomous Healthcare Institution of the Nizhny Novgorod Region "Research Institute of Clinical Oncology 'Nizhny Novgorod Regional Clinical Oncology Dispensary'"
  • Novosibirsk, Russia, 630091
    • Limited Liability Company Medical and Sanitary Unit "Clinician-Pretor Clinic"
  • 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
  • Obninsk, Russia, 249036
    • Federal State Budgetary Institution "National Medical Research Center of Radiology" of the Ministry of Health of the Russian Federation, Branch: P.A. Herzen Moscow Research Oncology Institute
  • Omsk, Russia, 644013
    • Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
  • Pushkin, Russia, 196603
    • Private Medical Institution "Euromedservice"
  • Pyatigorsk, Russia
    • State Budgetary Healthcare Institution of Stavropol Krai "Pyatigorsk Interdistrict Oncology Dispensary"
  • Rostov-on-Don, Russia, 344037
    • Federal State Budgetary Institution "National Medical Research Center of Oncology" of the Ministry of Health of the Russian Federation
  • Saint Petersburg, Russia, 197022
    • Limited Liability Company "EuroCityClinic"
  • Saint Petersburg, Russia, 195271
    • Private Healthcare Institution "RZD-Medicine Clinical Hospital" of Saint Petersburg
  • Saint Petersburg, Russia, 197022
    • Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
  • Tomsk, Russia, 634028
    • Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation
  • 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"
  • Yekaterinburg, Russia, 620036
    • State Autonomous Healthcare Institution of Sverdlovsk Region "Sverdlovsk Regional Oncology Dispensary"
• Uzbekistan
  • Tashkent, Uzbekistan, 100128
    • Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology, Tashkent Regional Branch

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. 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
4. At least one measurable lesion per RECIST 1.1
5. Karnofsky performance status ≥70%

6. 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
7. 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
8. Ability and willingness to comply with study protocol and procedures for the planned duration of participation

Maintenance Therapy Period (Period 2)

1. Registered objective response (stable disease or partial/complete response according to RECIST 1.1 criteria) to the therapy administered during the main study 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. Absence of a confirmed objective response to the administered therapy during the main study period, defined as failure to achieve disease stabilization or a partial/complete response according to RECIST v1.1
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, 100 mg/20 mL (5 mg/mL) per vial 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; Arcetux®; L01002; 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 8 weeks), or until disease progression or unacceptable toxicity Patients who received therapy with Erbitux® during the Main Period will be switched to therapy with RPH-002 starting from Week 9 of the Maintenance Period	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; vials of 10, 20, 50, and 100 mL containing 50, 100, 250, and 500 mg of the drug, respectively 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
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 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	At Visits 6 (Day 36), 12 (Day 78), and 18 (Day 120)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (%) (DCR; CR + PR + SD)	Disease Control Rate (DCR; CR + PR + SD), %, achieved within up to 18 weeks from the start of study treatment (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)
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
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 (%) with ADRs of severity grade ≥ 3	Proportion of patients (%) with ADRs of severity grade ≥ 3 according to CTCAE 5.0	Up to Day 365
Proportion of patients (%) with serious adverse events (SAEs)	Proportion of patients (%) with serious adverse events (SAEs)	Up to Day 365
Proportion of patients (%) with serious adverse drug reactions (SADRs)	Proportion of patients (%) with serious adverse drug reactions (SADRs)	Up to Day 365
Proportion of patients (%) who required discontinuation of treatment due to development of ADRs/SADRs	Proportion of patients (%) who required discontinuation of treatment due to development of ADRs/SADRs	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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	Up to Week 9 (Visit 9) in Period 2
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 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	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)
Disease Control Rate (%) (DCR; CR + PR + SD)	Disease control rate (DCR; CR + PR + SD) (%) 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; CR + PR + SD) (non-comparative evaluation in the RPH-002 group)	Disease Control Rate (%) (DCR; CR + PR + SD) for 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)
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2024
• Primary Completion (Actual): September 29, 2025
• Study Completion (Estimated): June 21, 2026

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: CL01002356

Drug and device information, study documents

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