Study of Cemiplimab in Adults With Cervical Cancer

• ClinicalTrials.gov Identifier: NCT03257267
• Recruitment Status: Completed
• First Posted: August 22, 2017
• Results First Posted: April 6, 2022
• Last Update Posted: July 11, 2023
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: July 26, 2017
• First Posted Date: August 22, 2017
• Results First Submitted Date: March 11, 2022
• Results First Posted Date: April 6, 2022
• Last Update Posted Date: July 11, 2023
• Actual Study Start Date: September 5, 2017
• Actual Primary Completion Date: March 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 11, 2022)

Overall Survival (OS) [ Time Frame: Time from randomization to the date of death due to any cause (assessed up to 40 months) ]

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.

• Original Primary Outcome Measures (submitted: August 17, 2017): Overall survival (OS) [ Time Frame: Time from randomization up to approximately 32 months ]

Current Secondary Outcome Measures (submitted: March 11, 2022)

• Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months) ]
  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.
• Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1 [ Time Frame: From date of randomization up to 40 months ]
  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.
• Duration of Response (DOR) Assessed Per RECIST 1.1 [ Time Frame: 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) ]
  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.
• 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 [ Time Frame: From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days) ]
  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.
• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death [ Time Frame: From date of randomization up to 40 months ]
  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.
• Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade [ Time Frame: From date of randomization up to 40 months ]
  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.

Original Secondary Outcome Measures (submitted: August 17, 2017)

• Progression-free survival (PFS) [ Time Frame: Time from randomization to the date of the first documented tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, up to approximately 32 months ]
• Overall Response Rate (ORR) [ Time Frame: Time from randomization to the date of the first documented tumor progression using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or death due to any cause, up to approximately 32 months ]
• Duration of response (DOR) [ Time Frame: Time between the date of first response (complete response or partial response) to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause, up to approximately 32 months ]
• Quality of life (QOL) [ Time Frame: Time from randomization up to 100 weeks ]
  Quality of life will be measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] [ Time Frame: Time from randomization up to approximately 32 months ]
  TEAEs include adverse events (AEs), serious adverse events (SAEs), deaths, and laboratory abnormalities.(SAEs), deaths, and laboratory abnormalities.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Cemiplimab
  Intravenous (IV) administration every 3 weeks (Q3W)
  Other Names:

  • REGN2810
  • Libtayo
• Drug: Investigator Choice (IC) Chemotherapy

  IC chemotherapy options include:

  1. Antifolate: Pemetrexed
  2. Topoisomerase 1 inhibitor: Topotecan or Irinotecan
  3. Nucleoside analogue: Gemcitabine
  4. 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.

Study Arms

• Experimental: Experimental Therapy
  Cemiplimab
  Intervention: Drug: Cemiplimab
• Active Comparator: Control Therapy
  Investigator choice (IC) chemotherapy
  Intervention: Drug: Investigator Choice (IC) Chemotherapy

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 12, 2021): 608
• Original Estimated Enrollment (submitted: August 17, 2017): 436
• Actual Study Completion Date: April 20, 2023
• Actual Primary Completion Date: March 15, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Canada, Greece, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03257267
• Other Study ID Numbers: R2810-ONC-1676; 2017-000350-19 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy
• Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• URL: https://vivli.org/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: June 2023