Volrustomig for Advanced Cervical Cancer

(eVOLVECervical Trial)

Recruiting at132 trial 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. ^{1 2 3 4 5}

What 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. ^{3 6 7 8 9}

Research Team

Eligibility 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.

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.

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

Treatment Details

Interventions

• Volrustomig (Virus Therapy)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer. [2023]

2. Egypt pubmed.ncbi.nlm.nih.gov

TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer. [2022]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab as a single agent for patients with MSI-H advanced endometrial carcinoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab in recurrent advanced cervical squamous carcinoma. [2018]

7. England pubmed.ncbi.nlm.nih.gov

RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer. [2022]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. [2021]