Clinical trial NCT03257267: Study of Cemiplimab in Adults With Cervical Cancer
Official title: An Open-Label, Randomized, Phase 3 Clinical Trial of REGN2810 Versus Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Squamous Cell Carcinoma (SCC)
Recurrent or Metastatic, Platinum-refractory Cervical Cancer
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-08-22
Enrollment: 608
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to compare overall survival (OS) for patients with recurrent or metastatic cervical cancer who have histology of squamous cell carcinoma (SCC) and who have any eligible histology treated with either cemiplimab or investigator's choice (IC) chemotherapy.

The secondary objectives performed among SCC patients and among all eligible histologies (SCC and adenocarcinoma/adenosquamous carcinoma (AC) are:

* To compare progression-free survival (PFS) of cemiplimab versus IC chemotherapy
* To compare objective response rate (ORR) (partial response \[PR\] + complete response \[CR\]) of cemiplimab versus IC chemotherapy per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* To compare the duration of response (DOR) of cemiplimab versus IC chemotherapy
* To compare the safety profiles of cemiplimab versus IC chemotherapy by describing adverse events (AE)
* To compare quality of life (QOL) for patients treated with cemiplimab versus IC chemotherapy using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)


Eligibility criteria: The criteria listed below are not intended to contain all considerations relevant to a patient's potential participation in this clinical trial.

Key Inclusion Criteria:

1. Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology, for which there is not a curative-intent option (surgery or radiation therapy with or without chemotherapy).

   * Acceptable histologies (squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma) as defined in the protocol
2. Tumor progression or recurrence after treatment with platinum therapy (must have been used to treat metastatic, persistent, or recurrent cervical cancer)
3. Patient must have measurable disease as defined by RECIST 1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
5. ≥18 years old
6. Adequate organ or bone marrow function
7. Received prior bevacizumab therapy or had clinically documented reason why not administered
8. Received prior paclitaxel therapy or had clinically documented reason why not administered

Key Exclusion Criteria:

1. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
2. Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
3. Prior treatment with other systemic immune-modulating agents that was

   1. within fewer than 4 weeks (28 days) of the enrollment date, or
   2. associated with irAEs of any grade within 90 days prior to enrollment, or
   3. associated with toxicity that resulted in discontinuation of the immune modulating agent
4. Active or untreated brain metastases
5. Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study drug cemiplimab or IC chemo)
6. Active infection requiring therapy
7. History of pneumonitis within the last 5 years
8. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
9. Concurrent malignancy other than cervical cancer and/or history of malignancy other than cervical cancer within 3 years of date of first planned dose of study drug cemiplimab or IC chemo), except for tumors with negligible risk of metastasis or death, such as adequately treated cutaneous squamous cell carcinoma or basal cell carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with hematologic malignancies (eg, chronic lymphocytic leukemia) are excluded.

Note: Other protocol defined Inclusion/Exclusion apply

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From first dose up to 90 following last dose (~42 months)
measure: Overall Survival (OS) in the SCC Population
timeFrame: From first dose up to 90 following last dose (~42 months)
Secondary outcomes:
measure: Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
timeFrame: Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months)
measure: Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1
timeFrame: From date of randomization up to 40 months
measure: Duration of Response (DOR) Assessed Per RECIST 1.1
timeFrame: Time from the date of first response to the date of the first documented progressive disease or death due to any cause (up to 40 months)
measure: Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales
timeFrame: From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death
timeFrame: From first dose up to 90 following last dose (~36 months)
measure: Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade
timeFrame: From first dose up to 90 following last dose (~36 months)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Orange
country: United States
facility: University of California Irvine
state: California
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Springfield
country: United States
facility: Cancer Research for the Ozarks
state: Missouri
city: Flushing
country: United States
facility: New York Presbyterian Queens
state: New York
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Laura and Issac Perlmutter Cancer Center at NYU Langone
state: New York
city: Pinehurst
country: United States
facility: First Health of the Carolinas Outpatient Cancer Center
state: North Carolina
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Austin
country: United States
facility: Texas Oncology, P.A.
state: Texas
city: Kogarah
country: Australia
facility: St. George Hospital
state: New South Wales
city: Tweed Heads
country: Australia
facility: Northern NSW Health District, The Tweed Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: St. John of God Subiaco Hospital
state: Western Australia
city: Aalst
country: Belgium
facility: OLV ziekenhuis Aalst, Medische oncologie- Radiotherapie
city: Brussels
country: Belgium
facility: Institut Bordet
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Leuven
country: Belgium
facility: UZLeuven Gynaelologic Oncology
city: Liège
country: Belgium
facility: CHC Saint Joseph
city: Liège
country: Belgium
facility: CHU Liège
city: Namur
country: Belgium
facility: CHU UCL Namur site Sainte Elisabeth
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Hosptial Sao Lucas da PUC de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: Rio Grande Do Sul
city: Itajai
country: Brazil
facility: Centro de Novos Tratamentos Itajai
state: Santa Catarina
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: São Paulo
city: Caxias do Sul
country: Brazil
facility: Instituto de Pesquisas Clinicas para Estudos Multicentricos - IPCEM
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCA
city: Rio de Janeiro
country: Brazil
facility: Instituto COI de Pesquisa
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hospital Maisonneuve-Rosemont
state: Quebec
city: Montréal
country: Canada
facility: Hopital Notre-Dame du Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Athens
country: Greece
facility: General Hospital of Athens Alexandra
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
city: Patras
country: Greece
facility: General Hospital of Patras
city: Thessaloniki
country: Greece
facility: Euromedica General Clinic, B'Oncology Clinic
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna
city: Lecce
country: Italy
facility: U.O Oncologia Medica P.O Vito Fazzi
city: Lecco
country: Italy
facility: Asst Lecco
city: Meldola
country: Italy
facility: Irst Irccs
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Reggio Emilia
country: Italy
facility: AUSL, IRCCS di Reggio Emilia
city: Roma
country: Italy
facility: Fondazione Policlinico Agostino Gemelli IRCCS di Roma
city: Rome
country: Italy
facility: Regina Elena National Cancer Institute
city: Matsuyama
country: Japan
facility: Shikoku Cancer Center
state: Ehime
city: Toon
country: Japan
facility: Ehime University Hospital
state: Ehime
city: Yoshida-gun
country: Japan
facility: Fukui University Hospital
state: Fukui
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Kawasaki
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kanagawa
city: Nakagami-gun
country: Japan
facility: University of the Ryukyus Hospital
state: Okinawa
city: Saitama
country: Japan
facility: Saitama Medical University
state: Saitama Prefecture
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-Ku
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Tokyo
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Saitama
country: Japan
facility: Saitama Cancer Center
state: Tokyo
city: Fukuoka
country: Japan
facility: National Kyushu Cancer Center
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Białystok
country: Poland
facility: Bialostockie Centrum Onkologii
city: Gdynia
country: Poland
facility: Szpitale Pomorskie
city: Gliwice
country: Poland
facility: Center and Institute of Oncology Gliwice
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im sw. Jana z Dukli
city: Poznań
country: Poland
facility: Greater Poland Cancer Center
city: Ivanovo
country: Russian Federation
facility: Regional Budgetary Institution of Healthcare Ivanovo Regional Oncology Dispensary
state: Ivanovo Region
city: Nal'chik
country: Russian Federation
facility: State Budgetary Healthcare Institution "Oncology Dispensary" of Ministry of Healthcare of the Kabardino-Balkarian Republic
state: Kabardino-Balkarian
city: Obninsk
country: Russian Federation
facility: A. Tsyb Medical Radiological Research Center
state: Kaluga
city: Krasnodar
country: Russian Federation
facility: State Budgetary Institution of Healthcare, Clinical Oncology Dispensary #1 of Ministry of Health of Krasnodar Region
state: Krasnodar Territory
city: Vsevolozhsk
country: Russian Federation
facility: State Budgetary Healthcare Institution Leningrad Regional Oncological Dispensary (SBHI "LROD")
state: Leningrad Region
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution ,Republican Clinical Oncological Dispensary of the Ministry of Healthcare of the Tatarstan Republic
state: Tatarstan
city: Omsk
country: Russian Federation
facility: Budgetary Institution of Healthcare of Omsk region Clinical Oncology Dispensary
city: Orenburg
country: Russian Federation
facility: State Budgetary Institution of Healthcare "Orenburg Regional Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: Saint- Petersburg State Budgetary institution of Healthcare "City Clinical Oncological Dispensary"
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Illes Balears
city: Barcelona
country: Spain
facility: Vall d´Hebron University Hospital
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Girona
country: Spain
facility: Instituto Catalan de Oncologia de Gerona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro CIOCC
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei City
country: Taiwan
facility: MacKay Memorial Hospital
city: Taipei
country: Taiwan
facility: Koo-Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde Beatson, West of Scotland Cancer care
city: London
country: United Kingdom
facility: University College Hospital
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust, Chelsea
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust, Sutton
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Oaknin A, Monk BJ, Vergote I, Cristina de Melo A, Kim YM, Lisyanskaya AS, Samouelian V, Kim HS, Gotovkin EA, Damian F, Chang CL, Takahashi S, Li J, Mathias M, Fury MG, Ivanescu C, Reaney M, LaFontaine PR, Lowy I, Harnett J, Chen CI, Tewari KS. EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer. Eur J Cancer. 2022 Oct;174:299-309. doi: 10.1016/j.ejca.2022.03.016. Epub 2022 Jul 31.
citation: Tewari KS, Monk BJ, Vergote I, Miller A, de Melo AC, Kim HS, Kim YM, Lisyanskaya A, Samouelian V, Lorusso D, Damian F, Chang CL, Gotovkin EA, Takahashi S, Ramone D, Pikiel J, Mackowiak-Matejczyk B, Guerra Alia EM, Colombo N, Makarova Y, Rischin D, Lheureux S, Hasegawa K, Fujiwara K, Li J, Jamil S, Jankovic V, Chen CI, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Mathias M, Fury MG, Oaknin A; Investigators for GOG Protocol 3016 and ENGOT Protocol En-Cx9. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med. 2022 Feb 10;386(6):544-555. doi: 10.1056/NEJMoa2112187.