Volrustomig for Advanced Cervical Cancer

(eVOLVECervical Trial)

Recruiting at 144 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: Any Age

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants, others

Disqualifiers: Metastatic disease, Autoimmune disorders, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 40 months

800 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether volrustomig (a PD-1/CTLA-4 bispecific monoclonal antibody) is effective and safe for women with advanced cervical cancer. It focuses on those whose cancer has not worsened after receiving platinum-based CCRT (chemotherapy and radiation). Participants will receive either volrustomig or a placebo (a substance with no therapeutic effect) to evaluate the new treatment's effectiveness. Women diagnosed with certain stages of cervical cancer, whose cancer has not spread beyond the cervix, and who have completed previous treatment without progression may be eligible to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that volrustomig is likely to be safe for humans?

Research shows that volrustomig, a type of immunotherapy, is undergoing tests for safety and effectiveness. Studies have found that treatments like volrustomig can reduce side effects in some patients, though some have discontinued due to side effects.

This treatment is in a late-stage trial, indicating it has passed earlier phases that assessed initial safety. These trials suggest the treatment is generally safe for further study, but doctors continue to monitor for any negative effects. Always consult your healthcare provider to understand what this might mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cervical cancer?

Volrustomig is unique because it works differently from existing treatments for advanced cervical cancer, such as chemotherapy and radiation. Unlike these standard options, which attack rapidly dividing cells in general, Volrustomig specifically targets cancer cells with a novel mechanism that researchers believe could lead to more effective and less toxic outcomes. This targeted approach has the potential to improve patient outcomes by minimizing damage to healthy cells, which is why researchers are eagerly investigating its possibilities.

What evidence suggests that volrustomig might be an effective treatment for advanced cervical cancer?

Research has shown that volrustomig, a new drug under study in this trial, may help treat advanced cervical cancer. Participants may receive volrustomig, which aids the immune system in attacking cancer cells in two ways. Similar drugs, such as cadonilimab, have effectively treated various types of cervical cancer. Early results suggest that patients experienced fewer side effects during treatment. This indicates that volrustomig could be a safe and effective option for those with advanced cervical cancer. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Volrustomig

Trial Overview

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.

How Is the Trial Designed?

Group I: Volrustomig Experimental Treatment 1 Intervention

Volrustomig

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

European Network for Gynaecological Oncological Trial Groups

Collaborator

Trials

4

Recruited

2,900+

Gynecologic Oncology Group Foundation

Collaborator

Trials

3

Recruited

1,300+

Published Research Related to This Trial

SHR-1701, a bispecific fusion protein targeting PD-L1 and TGFβ, shows promising clinical activity in patients with advanced or recurrent cervical cancer.

This study provides proof of principle that targeting the TGFβ pathway with bispecific antibodies could be an effective new therapeutic strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer. Miller, KM., Friedman, CF.[2023]

In a study of 80 patients with metastatic cervical cancer, the combination therapy of tumor-infiltrating lymphocytes (TILs) and anti-PD1 showed a 25% objective response rate, indicating a notable level of effectiveness in this challenging patient population.

The median progression-free survival (mPFS) was 6.1 months and median overall survival (mOS) was 11.3 months, suggesting that this combination therapy can significantly improve prognosis for patients with low microsatellite instability (MSI) and PDL1-negative tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer. Yin, H., Guo, W., Sun, X., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, has been approved for treating relapsed MSI-H endometrial cancer after chemotherapy, showing promise in restoring anti-tumor immunity by blocking PD-1 interactions.

Despite encouraging response rates in MSI-H patients, over 50% do not respond to pembrolizumab, highlighting the need for better understanding of MSI status and identifying specific patient populations that may benefit from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. Turinetto, M., Lombardo, V., Pisano, C., et al.[2022]

Increased expression of immune checkpoint markers TIGIT, Tim-3, and PD-1 was observed on NK and T cells in women with cervical cancer and pre-malignant lesions, indicating a state of immune exhaustion that could be targeted for therapy.

The study suggests that measuring these checkpoint markers, along with soluble PD-L1 levels, may help identify patients who are more likely to respond to immune checkpoint therapies, potentially improving treatment outcomes in cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis. Solorzano-Ibarra, F., Alejandre-Gonzalez, AG., Ortiz-Lazareno, PC., et al.[2022]

The RaPiDS study is a Phase II clinical trial designed to evaluate the safety and efficacy of balstilimab alone or in combination with zalifrelimab in patients with advanced cervical cancer who have not responded to first-line chemotherapy, involving a randomized 1:1 allocation of participants.

The primary goal of the study is to measure the objective response rate, while also assessing important secondary outcomes such as safety, duration of response, progression-free survival, overall survival, and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer. O'Malley, DM., Randall, LM., Jackson, CG., et al.[2022]

A heavily pretreated patient with recurrent advanced squamous cell carcinoma of the cervix, who had no remaining treatment options, experienced a remarkable response to the immune checkpoint inhibitor pembrolizumab.

This case highlights the potential of immune checkpoint inhibitors like pembrolizumab as a promising treatment option for patients with difficult-to-treat cervical carcinoma, although responses may vary among individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in recurrent advanced cervical squamous carcinoma. Martínez, P., Del Campo, JM.[2018]

In a phase II study involving 10 patients with advanced cervical cancer, the combination of atezolizumab and bevacizumab resulted in an objective response rate (ORR) of 0%, indicating that this treatment did not effectively shrink tumors as hoped.

Despite the lack of confirmed responses, the disease control rate was 60%, with a median progression-free survival of 2.9 months and overall survival of 8.9 months, suggesting some patients experienced stable disease, although safety concerns included two high-grade neurologic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. Friedman, CF., Snyder Charen, A., Zhou, Q., et al.[2021]

In a phase II trial involving 161 women with recurrent or metastatic cervical cancer, balstilimab, an anti-PD-1 antibody, showed an objective response rate (ORR) of 15%, indicating it can provide meaningful antitumor activity in this patient population.

The treatment was generally safe, with manageable side effects; the most common severe adverse events were immune-mediated enterocolitis (3.1%) and diarrhea (1.9%), suggesting that balstilimab has a favorable safety profile for patients who have previously undergone platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. O'Malley, DM., Oaknin, A., Monk, BJ., et al.[2022]

In a study involving 104 patients with recurrent or metastatic cervical cancer, the anti-PD-L1 antibody socazolimab showed a safety profile similar to other treatments in its class, with no treatment-related deaths reported.

The objective response rate (ORR) for patients receiving socazolimab was 15.4%, with a median progression-free survival of 4.44 months and a median overall survival of 14.72 months, indicating its potential efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of the Anti-PD-L1 mAb Socazolimab for Recurrent or Metastatic Cervical Cancer: a Phase I Dose-Escalation and Expansion Study. An, J., Tang, J., Li, BX., et al.[2023]

Citations

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Here we present dose-escalation data from a phase I, open-label, multicenter study in advanced solid tumors (NCT03530397). Methods: Eligible ...

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MEDI5752 monotherapy showed deep and durable antitumor activity in pts with advanced RCC, despite high rates of treatment D/C, particularly in the 1L setting.