AGEN2034 Alone or With AGEN1884 for Cervical Cancer

Not currently recruiting at 75 trial locations

Overseen By Agenus, Inc. Clinical Trial Information

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Agenus Inc.

Must not be taking: Immune checkpoints, Corticosteroids

Disqualifiers: CNS tumor, Autoimmune disease, Cardiovascular, 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: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies the safety and effectiveness of two treatments for advanced cervical cancer: AGEN2034 (an experimental treatment) alone or combined with AGEN1884 (another experimental treatment). It targets patients whose cancer has returned or worsened after initial platinum-based chemotherapy. The trial includes two groups: one receiving AGEN2034 with a placebo and the other receiving AGEN2034 with AGEN1884. Researchers seek patients with advanced cervical cancer who have relapsed after treatment. Participants should have a measurable tumor and no history of other significant health issues. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received systemic cytotoxic chemotherapy or biological therapy within 3 weeks before the first dose, and you should not be on systemic corticosteroid therapy within 7 days prior to the first dose, unless it's for specific conditions like daily replacement therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AGEN2034 is generally well-tolerated. Previous studies in patients with cervical and other cancers indicated it works by helping the immune system fight cancer. Most patients managed the treatment well, though some experienced side effects like tiredness or a rash.

The combination of AGEN2034 with AGEN1884 also shows promising safety data. Studies found that this combination is usually well-tolerated in similar patient groups. Some patients reported mild to moderate side effects, but these were manageable.

Both treatments have undergone testing in earlier studies, which helps ensure their safety for humans. However, it is important to discuss with a doctor what joining a trial could mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cervical cancer, such as chemotherapy and radiation, AGEN2034 and AGEN1884 are designed to harness the body’s own immune system to fight the cancer. AGEN2034 is a PD-1 inhibitor, which works by blocking a protein that prevents immune cells from attacking cancer cells. Combined with AGEN1884, a CTLA-4 inhibitor, these treatments aim to activate and enhance the immune response against the cancer more effectively. Researchers are excited about this approach because it offers the potential for more targeted treatment with possibly fewer side effects, which could significantly improve outcomes for patients with cervical cancer.

What evidence suggests that this trial's treatments could be effective for advanced cervical cancer?

Research shows that AGEN2034, one of the treatments in this trial, offers promising results for treating cervical cancer. Earlier studies demonstrated lasting positive effects, with some patients experiencing stable disease. AGEN2034 proved effective in about 42% of patients with recurring or spreading cervical cancer. Additionally, this trial will test the combination of AGEN2034 with AGEN1884, which previous studies have shown to benefit 31% of patients. These findings suggest that both treatments could be valuable options for individuals with advanced cervical cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Agenus Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced cervical cancer that has worsened after first-line platinum-based chemotherapy. Participants must have a specific type of tumor, measurable disease, good organ function, and an ECOG performance status of 0 or 1. They should not be pregnant, agree to use two barrier methods of contraception if applicable, and provide a tumor tissue sample.

Inclusion Criteria

My cervical cancer returned after first-line platinum-based treatment.

My cancer can be measured on scans according to specific criteria.

I am using two reliable forms of birth control during the study.

Exclusion Criteria

You have a history of severe allergic reactions to fully human monoclonal antibodies, a history of anaphylaxis, or uncontrolled asthma.

Has an inadequate washout period prior to first dose of study drug.

You have used illegal drugs or abused alcohol within the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AGEN2034 with placebo or AGEN1884 for a maximum of 24 months or until progression or unacceptable toxicity

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

What Are the Treatments Tested in This Trial?

Interventions

• AGEN1884
• AGEN2034

Trial Overview

The RaPiDS Phase 2 trial tests AGEN2034 alone (monotherapy) or combined with AGEN1884 (combination therapy) in patients with second-line cervical cancer. It's randomized and blinded but doesn't compare the two arms directly; each arm's efficacy is measured against historical controls.

How Is the Trial Designed?

Group I: AGEN2034 + Placebo Experimental Treatment 1 Intervention

AGEN2034 administered with placebo monotherapy: approximately 100 patients.

Group II: AGEN2034 + AGEN1884 Experimental Treatment 2 Interventions

AGEN2034 administered in combination with AGEN1884 (combination therapy): approximately 100 patients.

Who Is Running the Clinical Trial?

Agenus Inc.

Lead Sponsor

Trials

58

Recruited

4,900+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Published Research Related to This Trial

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

Irinotecan (CPT-11) has shown response rates of 13% to 20% in treating refractory or recurrent cervical cancer, indicating some level of efficacy in this challenging condition.

The combination of irinotecan with cisplatin has been studied, but the treatment is associated with significant hematologic and gastrointestinal toxicities, highlighting the need for further research to optimize safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in cervical cancer. Kavanagh, JJ., Verschraegen, CF., Kudelka, AP.[2018]

Patients with metastatic cervical cancer have a poor prognosis, with a median survival of only 8-13 months, highlighting the need for more effective treatment options beyond traditional chemotherapy, which is mainly palliative.

Recent advancements in understanding the immune response to Human papillomavirus (HPV) and the development of immunotherapies, along with next-generation sequencing for identifying actionable mutations, offer promising new avenues for treatment in cervical cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and targeted therapy for cervical cancer: an update. Menderes, G., Black, J., Schwab, CL., et al.[2016]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03104699

A Study of AGEN2034 in Advanced Tumors and Cervical ...

This is a 2-part trial: a Phase 1, open-label, dose-escalation study in participants with metastatic or locally advanced solid tumors, with a consecutive ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0090825821013160

Phase II study of the safety and efficacy of the anti-PD-1 ...

Balstilimab elicited promising and durable clinical activity in patients with recurrent/metastatic cervical cancer. · Tumor responses occurred irrespective of ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8887945/

Dual PD-1 and CTLA-4 Checkpoint Blockade Using ...

In that trial, the primary efficacy outcomes were a confirmed ORR of 15.0% (95% CI, 10.0 to 21.8) and a median DOR of 15.4 months (95% CI, 5.7 ...

4.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(19)49615-4/fulltext

Phase I/II, open-label, multiple ascending dose trial ...

AGEN2034 is pharmacologically active, well-tolerated PD-1 antagonist antibody, demonstrating early signals of clinical activity in cervical and ovarian cancers.

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2018.36.15_suppl.3086

Phase 1/2 open-label, multiple ascending dose trial of ...

At the time of data cut-off, 13 patients had stable disease, including 5 of 5 with ovarian cancer. AGEN2034 demonstrates a dose-proportional C ...

6.

clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT03894215

RaPiDS- A Phase 2 Study of Anti-PD-1 Independently or in ...

This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with ...