AGEN2034 Alone or With AGEN1884 for Cervical Cancer

Recruiting at 67 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

212 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug AGEN2034 and AGEN1884 for cervical cancer?

The research highlights the potential of immunotherapy, which includes drugs like AGEN2034 and AGEN1884, in treating cervical cancer by targeting immune checkpoints. This approach is promising due to a better understanding of how the immune system interacts with cervical cancer, although specific data on AGEN2034 and AGEN1884 is not provided. ^{1 2 3 4 5}

Is AGEN2034 alone or with AGEN1884 safe for humans?

In a large phase II trial, AGEN2034 (Balstilimab) and AGEN1884 (Zalifrelimab) showed a manageable safety profile when used together for cervical cancer, meaning they were generally safe for patients. ^{6 7 8 9 10}

How is the drug AGEN2034 alone or with AGEN1884 different for cervical cancer?

AGEN2034 and AGEN1884 are unique because they are part of a new class of treatments called immunotherapies, which work by helping the body's immune system fight cancer cells, unlike traditional chemotherapy that directly targets and kills cancer cells. ^{3 11 12 13 14}

What is the purpose of this trial?

This is a randomized, blinded, non-comparative, two-arm Phase 2 clinical trial to assess the efficacy and safety of AGEN2034 administered with placebo (Treatment Arm 1 - monotherapy) or with AGEN1884 (Treatment Arm 2- combination therapy) for treatment of patients with advanced cervical cancer who relapsed or progressed after receiving first-line platinum-based chemotherapy. The study is not intended to compare the efficacy of the 2 experimental arms. Rather, the efficacy of each arm will be evaluated against its relevant historical controls as appropriate.

Research Team

Medical Director

Principal Investigator

Agenus Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Association between Three Therapeutic Strategies and Clinical Outcomes of 2009 FIGO Stage IB2/IIA2 Cervical Cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis. [2023]

3. France pubmed.ncbi.nlm.nih.gov

[Evidence based of chemoradiotherapy in cervix carcinoma]. [2022]

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

Immunotherapy and targeted therapy for cervical cancer: an update. [2016]

5. China pubmed.ncbi.nlm.nih.gov

[The treatment of lymph nodes metastases of stage I and II cervical carcinoma]. [2006]

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

Balstilimab and other immunotherapy for recurrent and metastatic cervical cancer. [2022]

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

Integration of bevacizumab with chemotherapy doublets for advanced cervical cancer. [2018]

8. United States 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. [2021]

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

Irinotecan in cervical cancer. [2018]

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

Results of an early safety analysis of a study of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Comparison of platinum monotherapy with concurrent chemoradiation therapy versus platinum-based dual drug therapy with concurrent chemoradiation therapy for locally advanced cervical cancer: a systematic review and meta-analysis. [2022]

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

A Multi-Institutional Retrospective Analysis of Oncologic Outcomes for Patients With Locally Advanced Cervical Cancer Undergoing Platinum-Based Adjuvant Chemotherapy After Concurrent Chemoradiotherapy. [2022]

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

Final survival analysis of topotecan and paclitaxel for first-line treatment of advanced cervical cancer: An NRG oncology randomized study. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for metastatic and recurrent cervical cancer. [2021]