Volrustomig for Advanced Cervical Cancer
(eVOLVECervical Trial)
Recruiting in Palo Alto (17 mi)
+134 other locations
Age: Any Age
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AstraZeneca
Must not be taking: Immunosuppressants, others
Disqualifiers: Metastatic disease, Autoimmune disorders, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a new medication called Volrustomig to see if it can help women with advanced cervical cancer. The study focuses on those who haven't seen their cancer progress after initial treatment. Volrustomig might help stop or slow down the growth of cancer cells.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have used immunosuppressive medication within 14 days before the study starts, with some exceptions like certain steroids.
What data supports the effectiveness of the drug Volrustomig for advanced cervical cancer?
Research on similar treatments, like SHR-1701, a bispecific antibody targeting PD-L1 and TGFβ, shows promising results in advanced cervical cancer, suggesting that bispecific antibodies like Volrustomig could be effective. Additionally, the success of pembrolizumab, an anti-PD-1 antibody, in treating cervical cancer supports the potential of targeting PD-1 pathways in this disease.
12345What makes the drug Volrustomig unique for advanced cervical cancer?
Volrustomig is unique because it is a bispecific antibody that targets both PD-1 and CTLA-4, which are proteins that help cancer cells evade the immune system. This dual targeting approach is different from other treatments that typically focus on a single target, potentially offering a more comprehensive immune response against the cancer.
36789Eligibility Criteria
This trial is for women with high-risk advanced cervical cancer (stages IIIC to IVA) who haven't worsened after platinum-based chemoradiotherapy. Participants must be at least 15 years old, weigh over 35 kg, and have a performance status indicating they can carry out daily activities. They should not have other active cancers or severe illnesses and cannot take immunosuppressive drugs recently.Inclusion Criteria
My cancer did not worsen after combined chemotherapy and radiation, and I cannot undergo other curative treatments.
My organs and bone marrow are working well.
I can sign and understand the consent form.
+7 more
Exclusion Criteria
I have had cancer before, but it was either treated over 2 years ago, was a non-dangerous skin cancer, or was caught very early without spread.
I have or had a fistula connecting my bladder, colon, or rectum to my vagina.
I haven't taken immunosuppressive drugs in the last 14 days, except for allowed types like inhalers or local injections.
+14 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive Volrustomig or Placebo following randomization
40 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 years
Participant Groups
The study tests Volrustomig against a placebo in women with certain stages of cervical cancer following initial treatment. It's a phase III trial, meaning it's fairly late in the testing process and focuses on effectiveness and safety. The trial randomly assigns participants to either the drug or placebo group without them knowing which one they're getting.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: VolrustomigExperimental Treatment1 Intervention
Volrustomig
Group II: PlaceboPlacebo Group1 Intervention
Placebo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteAugusta, GA
Research SiteHouston, TX
Research SiteProvidence, RI
Research SiteSyracuse, NY
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
European Network for Gynaecological Oncological Trial GroupsCollaborator
Gynecologic Oncology Group FoundationCollaborator
References
Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer. [2023]SHR-1701, a bispecific fusion protein directed against PD-L1 and TGFβ, demonstrates promising clinical activity in advanced/recurrent cervical cancer. A recent study serves as a proof of principle that the TGFβ pathway may be successfully targeted, and that bispecific antibodies offer a novel therapeutic approach to do so. See related article by Feng et al., p. 5297.
TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer. [2022]We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative.
Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study. [2023]This study (ClinicalTrials.gov identifier, NCT03676959) is an open, phase I dose-escalation and expansion study investigating the safety and efficacy of the recombinant, fully human anti-programmed death ligand 1 (PD-L1) mAb socazolimab in patients diagnosed with recurrent or metastatic cervical cancer.
Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]Endometrial cancer can be characterized by high instability of microsatellites (MSI-H), a biomarker indicative of sensibility to immune checkpoint inhibitors (ICIs). The results of the KEYNOTE-158 trial led to the approval of pembrolizumab - a monoclonal, humanized IgG4 kappa anti-PD-1 antibody able to prevent T-cell PD-1/tumor cell PD-L1/2 interaction, thus restoring T-cell-mediated anti-tumor immunity - in MSI-H endometrial cancer relapsing after at least one line of chemotherapy (CT).
Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis. [2022]Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti-programmed cell death 1 (PD-1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin-domain containing-3 (Tim-3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim-3 and PD-1 on subsets of peripheral blood NK (CD56dim/neg CD16bright/dim/neg and CD56bright CD16dim/neg ) and T cells. The percentages of these cells were increased in women with cervical cancer and pre-malignant lesions. PD-1+ NK and T cells were likely to co-express TIGIT and/or Tim-3. These cells, with an apparently 'exhausted' phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)- and DNAX accessory molecule 1 (DNAM-1)-positive. PD-1int and PD-1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD-L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD-L1 and PD-1+ T cells in women with low-grade lesions. Within the cancer group, there were no significant correlations between sPD-L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD-L1 and total T cells and a correlation between sPD-L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre-cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.
Pembrolizumab in recurrent advanced cervical squamous carcinoma. [2018]No definitive cure is known for recurrent, persistent or metastatic cervical carcinoma. Chemotherapy remains the standard of care, although available options are scarce and do not provide satisfactory results. Immune checkpoint inhibitors have shown a strong and prolonged response in several types of cancer, although only in a subset of patients. Defining the profile of the patients likely to benefit from such treatment is a subject of active research. Here, we present a case of a heavily pretreated patient with recurrent advanced squamous cell carcinoma of the cervix who had exhausted all available treatment options and showed a striking response to the immune checkpoint inhibitor pembrolizumab.
RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer. [2022]Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.
Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. [2022]This phase II clinical trial evaluated the safety and antitumor activity of balstilimab, an anti-PD-1 antibody, in patients with previously-treated, recurrent/metastatic cervical cancer.
Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. [2021]There are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.