Study of Cemiplimab in Adults With Cervical Cancer

Squamous Cell Carcinoma (SCC) Clinical Trial

Official title:

An Open-Label, Randomized, Phase 3 Clinical Trial of REGN2810 Versus Investigator's Choice of Chemotherapy in Recurrent or Metastatic Cervical Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03257267
• Other study ID #: R2810-ONC-1676
• Secondary ID: 2017-000350-19
• Status: Completed
• Phase: Phase 3
• Start date: September 5, 2017
• Est. completion date: April 20, 2023

Study information

• Verified date: June 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 608
• Est. completion date: April 20, 2023
• Est. primary completion date: March 15, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Recurrent or Metastatic, Platinum-refractory Cervical Cancer
• Squamous Cell Carcinoma (SCC)
• Uterine Cervical Neoplasms

Intervention

Drug:
• Cemiplimab
Intravenous (IV) administration every 3 weeks (Q3W)
• Investigator Choice (IC) Chemotherapy
IC chemotherapy options include: Antifolate: Pemetrexed Topoisomerase 1 inhibitor: Topotecan or Irinotecan Nucleoside analogue: Gemcitabine Vinca alkaloid: Vinorelbine The only chemotherapy treatments allowed in the control arm are any of the 5 drugs that are listed as IC options above.

Locations

Country	Name	City	State
Australia	Royal Brisbane & Women's Hospital	Herston	Queensland
Australia	St. George Hospital	Kogarah	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	St. John of God Subiaco Hospital	Subiaco	Western Australia
Australia	Northern NSW Health District, The Tweed Hospital	Tweed Heads	New South Wales
Belgium	OLV ziekenhuis Aalst, Medische oncologie- Radiotherapie	Aalst
Belgium	Institut Bordet	Brussels
Belgium	Cliniques universitaires Saint-Luc	Bruxelles
Belgium	UZLeuven Gynaelologic Oncology	Leuven
Belgium	CHC Saint Joseph	Liège
Belgium	CHU Liège	Liège
Belgium	CHU UCL Namur site Sainte Elisabeth	Namur
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	São Paulo
Brazil	Instituto de Pesquisas Clinicas para Estudos Multicentricos - IPCEM	Caxias do Sul
Brazil	Centro de Novos Tratamentos Itajai	Itajai	Santa Catarina
Brazil	Liga Norte Riograndense Contra o Câncer	Natal	Rio Grande Do Norte
Brazil	Hosptial Sao Lucas da PUC de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericórdia de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto COI de Pesquisa	Rio de Janeiro
Brazil	Instituto Nacional de Cancer - INCA	Rio de Janeiro
Canada	Tom Baker Cancer Center	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Hospital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Hopital Notre-Dame du Centre Hospitalier de l'Universite de Montreal	Montréal	Quebec
Canada	Jewish General Hospital	Montréal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency	Vancouver	British Columbia
Greece	General Hospital of Athens Alexandra	Athens
Greece	University Hospital of Ioannina	Ioannina
Greece	General Hospital of Patras	Patras
Greece	Euromedica General Clinic, B'Oncology Clinic	Thessaloniki
Italy	Azienda Ospedaliero Universitaria di Bologna	Bologna
Italy	U.O Oncologia Medica P.O Vito Fazzi	Lecce
Italy	Asst Lecco	Lecco
Italy	Irst Irccs	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	AUSL, IRCCS di Reggio Emilia	Reggio Emilia
Italy	Fondazione Policlinico Agostino Gemelli IRCCS di Roma	Roma
Italy	Regina Elena National Cancer Institute	Rome
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Kyushu Cancer Center	Fukuoka
Japan	Kagoshima City Hospital	Kagoshima
Japan	St. Marianna University School of Medicine Hospital	Kawasaki	Kanagawa
Japan	The Cancer Institute Hospital of JFCR	Koto-Ku	Tokyo
Japan	Kurume University Hospital	Kurume	Fukuoka
Japan	Shikoku Cancer Center	Matsuyama	Ehime
Japan	Kyorin University Hospital	Mitaka	Tokyo
Japan	University of the Ryukyus Hospital	Nakagami-gun	Okinawa
Japan	Saitama Cancer Center	Saitama	Tokyo
Japan	Saitama Medical University	Saitama	Saitama Prefecture
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	Ehime University Hospital	Toon	Ehime
Japan	Fukui University Hospital	Yoshida-gun	Fukui
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Poland	Bialostockie Centrum Onkologii	Bialystok
Poland	Szpitale Pomorskie	Gdynia
Poland	Center and Institute of Oncology Gliwice	Gliwice
Poland	Centrum Onkologii Ziemi Lubelskiej im sw. Jana z Dukli	Lublin
Poland	Greater Poland Cancer Center	Poznan
Russian Federation	Regional Budgetary Institution of Healthcare Ivanovo Regional Oncology Dispensary	Ivanovo	Ivanovo Region
Russian Federation	State Autonomous Healthcare Institution ,Republican Clinical Oncological Dispensary of the Ministry of Healthcare of the Tatarstan Republic	Kazan	Tatarstan
Russian Federation	State Budgetary Institution of Healthcare, Clinical Oncology Dispensary #1 of Ministry of Health of Krasnodar Region	Krasnodar	Krasnodar Territory
Russian Federation	State Budgetary Healthcare Institution "Oncology Dispensary" of Ministry of Healthcare of the Kabardino-Balkarian Republic	Nal'chik	Kabardino-Balkarian
Russian Federation	A. Tsyb Medical Radiological Research Center	Obninsk	Kaluga
Russian Federation	Budgetary Institution of Healthcare of Omsk region Clinical Oncology Dispensary	Omsk
Russian Federation	State Budgetary Institution of Healthcare "Orenburg Regional Clinical Oncology Dispensary"	Orenburg
Russian Federation	Saint- Petersburg State Budgetary institution of Healthcare "City Clinical Oncological Dispensary"	Saint Petersburg
Russian Federation	State Budgetary Healthcare Institution Leningrad Regional Oncological Dispensary (SBHI "LROD")	Vsevolozhsk	Leningrad Region
Spain	Vall d´Hebron University Hospital	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Instituto Catalan de Oncologia de Gerona	Girona
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Universitario HM Sanchinarro CIOCC	Madrid
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Illes Balears
Spain	Fundacion Instituto Valenciano de Oncologia	Valencia
Spain	Hospital Universitario La Fe	Valencia
Spain	Hospital Clinico Universitario Lozano Blesa	Zaragoza
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Koo-Foundation Sun Yat-Sen Cancer Center	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	MacKay Memorial Hospital	Taipei City
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	NHS Greater Glasgow and Clyde Beatson, West of Scotland Cancer care	Glasgow
United Kingdom	Royal Marsden NHS Foundation Trust, Chelsea	London
United Kingdom	University College Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Royal Marsden NHS Foundation Trust, Sutton	Sutton
United States	Texas Oncology, P.A.	Austin	Texas
United States	New York Presbyterian Queens	Flushing	New York
United States	Northwell Health	Lake Success	New York
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Laura and Issac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	University of California Irvine	Orange	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates	Phoenix	Arizona
United States	First Health of the Carolinas Outpatient Cancer Center	Pinehurst	North Carolina
United States	Cancer Research for the Ozarks	Springfield	Missouri
United States	Arizona Oncology Associates	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Greece,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.	Time from randomization to the date of death due to any cause (assessed up to 40 months)
Secondary	Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who do not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.	Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months)
Secondary	Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1	ORR was defined as the number of participants who achieved complete response (CR) or partial response (PR) as per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm) (<1 centimeter [cm]). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	From date of randomization up to 40 months
Secondary	Duration of Response (DOR) Assessed Per RECIST 1.1	DOR was defined as the time from the date of first response (CR or PR) to the date of the first documented progressive disease (per RECIST 1.1) or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Participants who never progress while being followed was censored at the last valid tumor measurement. DOR was determined by Kaplan-Meier estimate.	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)
Secondary	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	EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.	From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days)
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death	An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A TEAE was defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs, serious TEAEs, and TEAEs leading to death were reported.	From date of randomization up to 40 months
Secondary	Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade	Laboratory parameters included hematology, electrolytes, chemistry (other), and liver function. Clinically significant abnormalities were determined by the investigator based on NCI-CTCAE Grade where Grade 1 = Mild, Grade 2 = moderate, Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. Participants with at least 1 lab abnormality Graded 3/4 in hematology, electrolytes, chemistry (other), or liver function reported.	From date of randomization up to 40 months