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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests AK104, an experimental drug for individuals with a specific type of cervical cancer that has recurred or spread after treatment. The study aims to determine the effectiveness and safety of AK104 for these patients. It targets those who have tried treatments like chemotherapy but still have measurable disease. If high-grade neuroendocrine cervical cancer has returned or spread, and up to two prior treatments have been received, this trial might be suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that AK104 is likely to be safe for humans?

Research has shown that cadonilimab, also known as AK104, is safe and generally well-tolerated by patients. Studies have found that even for individuals whose cancer does not respond to other treatments, cadonilimab maintains manageable safety with no severe side effects reported. For patients with PD-L1 positive cancers, the treatment has demonstrated good results, and PD-L1 negative patients have also tolerated it well. This indicates that the treatment is not only effective for some but also has a safety profile acceptable to many patients. ^{1 2 3 4 5}

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

Unlike the standard treatments for cervical cancer, which often include chemotherapy and radiation, AK104 offers a novel approach by targeting both PD-1 and CTLA-4 pathways. This dual-action mechanism potentially enhances the immune system's ability to fight cancer cells more effectively. Researchers are particularly excited because AK104, also known as cadonilimab, may provide new hope for cases where the cancer has returned or spread, offering a promising option for patients with recurrent or metastatic neuroendocrine cervical cancer.

What evidence suggests that AK104 might be an effective treatment for cervical cancer?

Research has shown that cadonilimab (AK104), a special type of antibody, may help treat cervical cancer that has returned or spread. Studies have linked cadonilimab to positive outcomes in people with this type of cancer, including tumor shrinkage. Although nearly all participants experienced side effects, the ability to control tumor growth is significant. This suggests that cadonilimab could be a valuable option for difficult cases of cervical cancer. Participants in this trial will receive cadonilimab to evaluate its effectiveness and safety in treating recurrent or metastatic neuroendocrine cervical cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Amir Jazaeri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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

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

My cervical cancer has returned or spread and worsened after platinum-based chemotherapy.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5537

Real-world efficacy and safety of cadonilimab (PD-1/CTLA- ... Results: 96 patients treated with cadonilimab monotherapy or cadonilimab plus chemotherapy with/without radiotherapy were enrolled. The median ...

2. akesobio.com akesobio.com/en/media/akeso-news/250321/

Akeso's Cadonilimab Combined with Concurrent ... The study evaluates the global first-in-class PD-1/CTLA-4 bispecific antibody, cadonilimab (AK104), in combination with concurrent chemoradiotherapy (CCRT)

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12363071/

Clinical efficacy and safety of Cadonilimab in the treatment of ... Specifically, the survival rate for patients with recurrent and metastatic cervical cancer is only 17% [6], while the 5-year survival rate for ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06140589

NCT06140589 | Exploring the Efficacy, Safety and Cost ... Efficacy of Cadonilimab in the treatment of persistent, recurrent or metastatic cervical cancer, Objective response rate (ORR) was used to evaluate the efficacy ...

5. nature.com nature.com/articles/s41571-024-00962-3

Cadonilimab is effective and safe in recurrent cervical cancer Treatment-related adverse events of any grade occurred in virtually all participants, and grade 3–4 events occurred in 82% and 79% of patients ...

6. akesobio.com akesobio.com/media/1826/2-ak104-2022-sgo-%E5%AE%AB%E9%A2%88%E7%99%8C-2%E6%88%963l.pdf

Efficacy and Safety of Cadonilimab, An Anti-PD Pts with PD-L1 positive(CPS≥1), the ORR was 43.8%;. • Pts with PD-L1 negative(CPS<1), the ORR was 16.7%. • Cadonilimab monotherapy is safe and well tolerated in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05063916

NCT05063916 | Phase II Study of AK104 (Cadonilimab) for ... This is a Phase 2, single center, open-label, single-arm study designed to evaluate the efficacy, safety, tolerability, and immunogenicity of AK104 monotherapy ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12405967/

A Systematic Review and Single‐Arm Meta‐Analysis - PMC Cadonilimab (AK104) is a bispecific antibody that simultaneously targets programmed cell death‐1 and cytotoxic T‐lymphocyte antigen‐4.

9. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1582299/full

The comparison of efficacy and safety between ... Patients with recurrent or metastatic cervical cancer (R/M CC) have a poor prognosis, with a five-year survival rate of less than 50% (4–6).