Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer (eVOLVE-Cervical) (eVOLVECervical)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-centre, Global Study of Volrustomig in Women With High Risk Locally Advanced Cervical Cancer Who Have Not Progressed Following Platinum-based, Concurrent Chemoradiation Therapy (eVOLVE-Cervical)

This is a phase III, randomized, double-blind, placebo-controlled, multi-center, global study to explore the efficacy and safety of volrustomig in women with high-risk LACC (FIGO 2018 stage IIIC to IVA cervical cancer with lymph node involvement) who have not progressed following platinum-based CCRT.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Cervical Cancer
• Intervention / Treatment: Other: Placebo; Biological: Volrustomig

Detailed Description

Women with locally advanced cervical cancer will be randomized in a 1:1 ratio to receive treatment with Volrustomig or Placebo.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Brazil
  • Barretos, Brazil, 14784-400
    • Not yet recruiting
    • Research Site
  • Belo Horizonte, Brazil, 30130-100
    • Not yet recruiting
    • Research Site
  • Curitiba, Brazil, 80730-150
    • Not yet recruiting
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  • Fortaleza, Brazil, 60336-045
    • Not yet recruiting
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  • Porto Alegre, Brazil, 90110-270
    • Not yet recruiting
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  • Porto Alegre, Brazil, 90619-900
    • Not yet recruiting
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  • Porto Velho, Brazil, 76834-899
    • Not yet recruiting
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  • Rio de Janeiro, Brazil, 20231-050
    • Not yet recruiting
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  • Salvador, Brazil, 40050 410
    • Not yet recruiting
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  • Sao Paulo, Brazil, 1323001
    • Not yet recruiting
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  • São Paulo, Brazil, 01246-000
    • Not yet recruiting
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  • Teresina, Brazil, 64049-200
    • Not yet recruiting
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• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Withdrawn
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    • Toronto, Ontario, Canada, M4N 3M5
      • Not yet recruiting
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    • Toronto, Ontario, Canada, M5G 2M9
      • Not yet recruiting
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  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Not yet recruiting
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    • Montreal, Quebec, Canada, H3G 1A4
      • Recruiting
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    • Ste-Foy, Quebec, Canada, G1V 4G2
      • Withdrawn
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• China
  • Beijing, China, 100730
    • Not yet recruiting
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  • Changde, China, 415003
    • Not yet recruiting
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  • Changsha, China, 410013
    • Not yet recruiting
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  • Changsha, China, 410008
    • Not yet recruiting
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  • Chengdu, China, 610041
    • Not yet recruiting
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  • Chongqing, China, 400030
    • Not yet recruiting
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  • Fuzhou, China, 350014
    • Not yet recruiting
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  • Guangzhou, China, 510060
    • Not yet recruiting
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  • Guangzhou, China, 510120
    • Not yet recruiting
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  • Hangzhou, China, 310022
    • Not yet recruiting
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  • Harbin, China, 150081
    • Not yet recruiting
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  • Kunming, China, 650118
    • Not yet recruiting
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  • Lanzhou, China, 730000
    • Not yet recruiting
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  • Lanzhou, China, 730050
    • Not yet recruiting
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  • Luzhou, China, 646000
    • Not yet recruiting
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  • Nanchang, China, 330006
    • Not yet recruiting
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  • Nanchang, China, 330029
    • Not yet recruiting
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  • Shandong, China
    • Not yet recruiting
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  • Shanghai, China, 200032
    • Not yet recruiting
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  • Shanghai, China, 200080
    • Not yet recruiting
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  • Shenyang, China, 110004
    • Not yet recruiting
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  • TianJin, China, 300060
    • Not yet recruiting
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  • Wuhan, China, 430022
    • Not yet recruiting
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  • Wuhan, China, 430030
    • Not yet recruiting
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  • Xi'an, China, 710061
    • Not yet recruiting
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  • Yinchuan, China, 750004
    • Not yet recruiting
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  • Zhengzhou, China, 450008
    • Not yet recruiting
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  • Zhengzhou, China
    • Not yet recruiting
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• Denmark
  • Aarhus N, Denmark, 8200
    • Not yet recruiting
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  • København Ø, Denmark, 2100
    • Not yet recruiting
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  • Odense C, Denmark, 5000
    • Not yet recruiting
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• India
  • Calicut, India, 673601
    • Not yet recruiting
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  • Jaipur, India, 302017
    • Recruiting
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  • Lucknow, India, 226003
    • Not yet recruiting
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  • Madurai, India, 625107
    • Recruiting
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  • Mohali, India, 160055
    • Recruiting
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  • Nagpur, India, 440001
    • Recruiting
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  • Nashik, India, 422009
    • Recruiting
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  • Nashik, India, 422011
    • Recruiting
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  • New Delhi, India, 11029
    • Recruiting
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  • Vadodara, India, 391760
    • Recruiting
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• Italy
  • Napoli, Italy, 80131
    • Not yet recruiting
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  • Rome, Italy, 00168
    • Recruiting
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  • Turin, Italy, 10128
    • Not yet recruiting
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• Japan
  • Fukuoka-shi, Japan, 812-8582
    • Recruiting
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  • Hidaka-shi, Japan, 350-1298
    • Recruiting
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  • Kagoshima-shi, Japan, 890-8520
    • Recruiting
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  • Koto-ku, Japan, 135-8550
    • Recruiting
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  • Kurume-shi, Japan, 830-0011
    • Recruiting
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  • Maebashi-shi, Japan, 371-8511
    • Recruiting
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  • Matsuyama-shi, Japan, 791-0280
    • Recruiting
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  • Morioka-shi, Japan, 028-3695
    • Recruiting
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  • Nagoya-shi, Japan, 464-8681
    • Recruiting
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  • Nakagami-gun, Japan, 903-0215
    • Recruiting
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  • Osaka-shi, Japan, 541-8567
    • Withdrawn
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  • Sapporo-shi, Japan, 003-0804
    • Recruiting
    • Research Site
  • Sapporo-shi, Japan, 060-8638
    • Withdrawn
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  • Shinjuku-ku, Japan, 160-8582
    • Recruiting
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  • Suita-shi, Japan, 565-0871
    • Recruiting
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  • Sunto-gun, Japan, 411-8777
    • Recruiting
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  • Toon-Shi, Japan, 791-0295
    • Recruiting
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• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
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  • Seoul, Korea, Republic of, 06351
    • Recruiting
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  • Seoul, Korea, Republic of, 03080
    • Recruiting
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  • Seoul, Korea, Republic of, 5505
    • Recruiting
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• Mexico
  • Ciudad de México, Mexico, 03240
    • Not yet recruiting
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  • Coyoacan, Mexico, 04380
    • Not yet recruiting
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  • Culiacan, Mexico, 80040
    • Not yet recruiting
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  • Guadalajara, Mexico, 44650
    • Not yet recruiting
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  • Guadalajra, Mexico, 44260
    • Not yet recruiting
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  • Mexico, Mexico, 14080
    • Not yet recruiting
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  • Monterrey, Mexico, 64460
    • Not yet recruiting
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  • México, Mexico, 04700
    • Not yet recruiting
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• Norway
  • Oslo, Norway, 424
    • Not yet recruiting
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  • Trondheim, Norway, 7030
    • Not yet recruiting
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• Peru
  • Concepción, Peru, 12125
    • Not yet recruiting
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  • Lima, Peru, LIMA 29
    • Not yet recruiting
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  • Lima, Peru, 15036
    • Not yet recruiting
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  • Lima, Peru, 15038
    • Not yet recruiting
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  • Lima, Peru, 15102
    • Not yet recruiting
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• Poland
  • Białystok, Poland, 15-027
    • Recruiting
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  • Gdańsk, Poland, 80-214
    • Not yet recruiting
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  • Gliwice, Poland, 44-101
    • Not yet recruiting
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  • Kraków, Poland, 30-348
    • Not yet recruiting
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  • Poznan, Poland, 61-866
    • Not yet recruiting
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  • Warszawa, Poland, 02-781
    • Not yet recruiting
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  • Wroclaw, Poland, 53-413
    • Not yet recruiting
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  • Łódź, Poland, 90-513
    • Not yet recruiting
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• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Not yet recruiting
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• Spain
  • Barcelona, Spain, 08036
    • Not yet recruiting
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  • Barcelona, Spain, 8035
    • Not yet recruiting
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  • Cordoba, Spain, 14004
    • Not yet recruiting
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  • Girona, Spain, 17007
    • Not yet recruiting
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  • Hospitalet deLlobregat, Spain, 08907
    • Not yet recruiting
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  • La Coruna, Spain, 15006
    • Not yet recruiting
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  • Madrid, Spain, 28040
    • Not yet recruiting
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  • Madrid, Spain, 28034
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28041
    • Not yet recruiting
    • Research Site
  • Madrid, Spain, 28046
    • Withdrawn
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  • Palma de Mallorca, Spain, 07010
    • Not yet recruiting
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  • Valencia, Spain, 46010
    • Not yet recruiting
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  • Valencia, Spain, 46009
    • Not yet recruiting
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 81362
    • Recruiting
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  • Kaohsiung city, Taiwan, 833
    • Recruiting
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  • New Taipei, Taiwan, 220
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 40705
    • Recruiting
    • Research Site
  • Tainan, Taiwan
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 11217
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 10449
    • Recruiting
    • Research Site
  • Taoyuan, Taiwan, 333
    • Recruiting
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• Turkey
  • Ankara, Turkey, 06100
    • Not yet recruiting
    • Research Site
  • Ankara, Turkey, 06490
    • Not yet recruiting
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  • Istanbul, Turkey, 32098
    • Not yet recruiting
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  • Istanbul, Turkey, 34214
    • Not yet recruiting
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Withdrawn
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  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Not yet recruiting
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    • Tucson, Arizona, United States, 85711
      • Not yet recruiting
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  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Not yet recruiting
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  • California
    • La Jolla, California, United States, 92093
      • Not yet recruiting
      • Research Site
    • West Hollywood, California, United States, 90048
      • Withdrawn
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  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
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    • Augusta, Georgia, United States, 30912
      • Not yet recruiting
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    • Savannah, Georgia, United States, 31405
      • Not yet recruiting
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  • Illinois
    • Melrose Park, Illinois, United States, 60160
      • Not yet recruiting
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  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Not yet recruiting
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  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Not yet recruiting
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    • New Orleans, Louisiana, United States, 70121
      • Not yet recruiting
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    • Shreveport, Louisiana, United States, 71103
      • Recruiting
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  • New York
    • New York, New York, United States, 10016
      • Not yet recruiting
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    • Syracuse, New York, United States, 13210
      • Not yet recruiting
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  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Withdrawn
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    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
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  • Oregon
    • Eugene, Oregon, United States, 97401
      • Not yet recruiting
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  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Withdrawn
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  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Not yet recruiting
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  • Texas
    • Dallas, Texas, United States, 75390
      • Not yet recruiting
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    • Fort Worth, Texas, United States, 76104
      • Not yet recruiting
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    • Houston, Texas, United States, 77030
      • Not yet recruiting
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    • Tyler, Texas, United States, 75702
      • Not yet recruiting
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  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Not yet recruiting
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    • Richmond, Virginia, United States, 23298
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

1. Female.
2. Aged at least 15 years at the time of screening.
3. Body weight > 35 kg.
4. Histologically documented FIGO 2018 Stage IIIC to IVA cervical adenocarcinoma, cervical squamous carcinoma, or cervical adenosquamous carcinoma, with lymph node involvement.
5. Initial staging procedures performed no more than 42 days prior to the first dose of CCRT.
6. Provision of tumor sample to assess the PD-L1 expression.
7. Must not have progressed following CCRT, participants with persistent disease after definitive CCRT must not be amenable to other available therapies with curative intent.
8. WHO/ECOG performance status of 0 or 1.
9. Adequate organ and bone marrow function.
10. Capable of providing signed informed consent.

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Diagnosis of small cell (neuroendocrine) or mucinous adenocarcinoma of cervical cancer.
2. Evidence of metastatic disease.
3. Intent to administer a fertility-sparing treatment regimen.
4. History of organ transplant.
5. Active or prior documented autoimmune or inflammatory disorders.
6. Uncontrolled intercurrent illness.
7. History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
8. Unresolved toxicities from previous CCRT except for irreversible toxicity that is not reasonably expected to be exacerbated.
9. Prior history or presence of vesicovaginal, colovaginal, or rectovaginal fistula.
10. History of anaphylaxis to any biologic therapy or vaccine.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control).
12. Patients who have undergone a previous hysterectomy, including a supracervical hysterectomy, or will have a hysterectomy as part of their initial cervical cancer therapy.
13. Any prior (besides prior CCRT) or concurrent treatment for cervical cancer.
14. Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
15. Exposure to immune mediated therapy prior to the study for any indication.
16. Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
17. Participants with a known allergy or hypersensitivity to the study intervention, or any excipients of the study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; IV Infusion; Other Names: Saline
Experimental: Volrustomig	Biological: Volrustomig; IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) in participants with PD-L1 expression based on the investigator assessment	PFS is defined as the time from date of randomization until RECIST 1.1- defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier.	The study duration will be approximately 40 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) in participants regardless of PD-L1 expression based on the investigator assessment	PFS is defined as the time from date of randomization until RECIST 1.1-defined radiological progression or histopathologically confirmed progression as assessed by the Investigator or death due to any cause, whichever occurs earlier.	The study duration will be approximately 40 months
Overall Survival (OS) in participants regardless of PD-L1 expression.	OS defined as time from randomization until the date of death due to any cause.	The study duration will be approximately 6 years.
Overall Survival (OS) in participants with PD-L1 expression	OS defined as time from randomization until the date of death due to any cause.	The study duration will be approximately 6 years.
Objective Response Rate (ORR) in participants with PD-L1 expression/regardless of PD-L1 expression.	ORR is defined as the proportion of participants who have a CR or PR, as determined by Investigator per RECIST 1.1	The study duration will be approximately 40 months
Duration of Response (DoR) in participants with a CR or PR in the PD-L1 expression analysis set/FAS.	DoR in participants with a CR or PR: Time from date of first detection of CR or PR until the date of RECIST 1.1-defined radiological progression or histopathologically confirmed progression.	The study duration will be approximately 40 months
Time to First Subsequent Therapy or death (TFST) in the PD-L1 expression analysis set/FAS	TFST: The time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.	The study duration will be approximately 40 months
Time to second progression or death (PFS2) in the PD-L1 expression analysis set/FAS.	PFS2: The time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.	The study duration will be approximately 6 years.
PFS by BICR in the PD-L1 expression analysis set/FAS.	Endpoints based on the PFS by BICR assessment according to RECIST 1.1.	The study duration will be approximately 40 months
The incidence of local progression, and distant disease progression as the first documented progression event in the PD-L1 expression analysis set/FAS.	Incidence of Local Progression, and Distant Disease Progression: Number and percentage of participants who develop local progression, distant disease recurrence.	The study duration will be approximately 40 months
PK of Volrustomig	Concentration of Volrustomig in serum.	The study duration will be approximately 40 months.
The immunogenicity of volrustomig.	Incidence of ADAs against volrustomig in serum.	The study duration will be approximately 40 months
Incidence of adverse events of Volrustomig compared to placebo;	An AE is definded as the development of any untoward medical occurrence (other than progression of the malignancy under evaluation) in a patient or clinical study participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.	The study duration will be approximately 40 months.
Participant-reported disease-related symptoms	Change from baseline as measured by the European Organization for Research and Treatment of Cancer IL318 (EORTC IL318, Symptom Experience subscale of the EORTC Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24)). The score of scale for EORTC IL318 is from 1-4.	The study duration will be approximately 40 months.
Participant-reported physical functioning	Change from baseline of physical functioning as measured by the Patient Reported Outcomes Measurement Information System - Short Form - Physical Functioning 8c (PROMIS SF-PF 8c). The score of scale for PROMIS SF-PF 8c is from 1-5.	The study duration will be approximately 40 months.
Participant-reported global health status/Quality of Life.	Change from baseline of Global Health Status/ Quality of Life (GHS/QoL) as measured by the European Organization for Research and Treatment of Cancer IL172 (EORTC IL172). The score of scale for EORTC IL172 is from 1-7.	The study duration will be approximately 40 months.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Gynecologic Oncology Group Foundation; European Network for Gynaecological Oncological Trial Groups

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2023
• Primary Completion (Estimated): February 19, 2027
• Study Completion (Estimated): October 24, 2029

Study Registration Dates

• First Submitted: September 4, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Volrustomig; Locally Advanced Cervical Cancer;; Adolescent and Young Adult
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms
• Other Study ID Numbers: D7984C00002; GOG-3092 (Other Identifier: Gynecologic Oncology Group Foundation); ENGOT-cx19/GEICO (Other Identifier: European Network for Gynaecological Oncological Trial groups); 165663 (Registry Identifier: FDA-IND); 2023-504374-38-00 (Other Identifier: EU CT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes