AK104 for Cervical Cancer

Overseen By Michael Frumovitz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Other cervical cancer types, Brain metastases, Active infections, Autoimmune disease, Cardio-cerebrovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing AK104, a treatment that helps the immune system fight cancer, in adults whose high-grade neuroendocrine cervical cancer has come back or spread after previous treatments.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like anticancer therapy or immunomodulatory agents within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug AK104 for cervical cancer?

The research suggests that targeting proteins like AKAP4, which is associated with cervical cancer growth, can be effective. AKAP4 was found to be involved in the growth and spread of cervical cancer cells, and reducing its levels led to decreased tumor growth in mice, indicating potential for immunotherapy targeting similar pathways. ^{1 2 3 4 5}

What makes the drug AK104 unique for treating cervical cancer?

AK104 is unique because it targets A-kinase anchor protein 4 (AKAP4), which is associated with the growth and spread of cervical cancer cells. By focusing on this specific protein, AK104 may offer a novel approach to slowing down or stopping the progression of the disease, unlike traditional chemotherapy that targets rapidly dividing cells in general. ^{1 4 6 7 8}

Research Team

Michael Frumovitz, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults over 18 with recurrent or metastatic high-grade neuroendocrine cervical cancer that worsened after platinum-based chemotherapy can join. They should have tried no more than two systemic therapies and not be candidates for surgery/radiation. Participants need measurable lesions, good performance status, proper organ function, a negative pregnancy test if applicable, and agree to use contraception.

Inclusion Criteria

Ability to provide written and signed informed consent

I am 18 years old or older.

My cancer can be measured by scans, excluding any previously treated with radiation.

Exclusion Criteria

I have previously been treated with experimental cancer vaccines or drugs that target the immune system.

Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or the follow-up period of an interventional study

My cervical cancer is not a high-grade neuroendocrine type.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AK104 monotherapy to evaluate efficacy, safety, tolerability, and immunogenicity

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• AK104

Trial Overview The trial is testing AK104 (Cadonilimab), an investigational drug given as monotherapy to see how effective and safe it is for patients who've had previous treatments for their advanced cervical cancer. It's an open-label study where everyone gets the same treatment.

Participant Groups

Group I: AK104 Experimental Treatment 1 Intervention

cadonilimab) can help to control neuroendocrine cervical cancer that is recurrent (has come back after treatment) or metastatic (has spread).

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Pembrolizumab, an antibody targeting the PD-1 receptor, has shown limited effectiveness as a standalone treatment for recurrent and/or metastatic cervical cancer in the general patient population, but it has received accelerated approval from the FDA for patients with PD-L1-expressing tumors due to its potential for durable responses.

Future research is focusing on combining pembrolizumab with other therapies like chemotherapy and radiotherapy, and identifying additional biomarkers beyond PD-L1 expression will be crucial to better select patients who are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of cervical cancer. Marret, G., Borcoman, E., Le Tourneau, C.[2020]

Cervical cancer affects a significant number of patients, with 15-61% developing advanced disease after diagnosis, and current treatment options have not improved the 5-year survival rate over the last 30 years.

Recent advancements in tumor genomic testing have identified a 28.4% actionability rate for targetable mutations in cervical cancer, indicating potential for personalized treatment strategies using targeted agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer. Crowley, FJ., O'Cearbhaill, RE., Collins, DC.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Gene silencing of A-kinase anchor protein 4 inhibits cervical cancer growth in vitro and in vivo. [2013]

2. Cyprus pubmed.ncbi.nlm.nih.gov

Evaluation of the possible benefits of post-radiotherapy surgery after concomitant chemoradiotherapy with a new radio-sensitizing regimen (irinotecan / CPT-11, interferon A2b and amifostine) for advanced-stage cervical carcinoma. Preliminary results of a pilot phase-II study. [2018]

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

Development of a platform for systemic antiangiogenesis therapy for advanced cervical cancer. [2015]

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

AKR1C1 Contributes to Cervical Cancer Progression via Regulating TWIST1 Expression. [2021]

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

Pembrolizumab for the treatment of cervical cancer. [2020]

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

Clinical implications of aldo-keto reductase family 1 member C3 and its relationship with lipocalin 2 in cancer of the uterine cervix. [2017]

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

CD109 mediates tumorigenicity and cancer aggressiveness via regulation of EGFR and STAT3 signalling in cervical squamous cell carcinoma. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer. [2022]