Etrumadenant + Zimberelimab for Sarcoma

Recruiting at 6 trial locations

Overseen By Sujana Movva, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: PD-1 inhibitors, Adenosine agents

Disqualifiers: Active CNS metastases, Uncontrolled illness, 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 weeks

16 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, etrumadenant (AB928) and zimberelimab (AB122), to determine their effectiveness in treating advanced dedifferentiated liposarcoma (DDLS), a type of cancer that has spread or cannot be surgically removed. The goal is to assess whether this combination works better than existing treatments for this aggressive cancer. Individuals with DDLS that has recurred after treatment or spread to other parts of the body might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring 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 must not have taken certain medications that interact with etrumadenant, such as specific BCRP and P-gp substrates, or strong CYP3A4 inducers and inhibitors, within 4 weeks or 5 half-lives before starting the trial.

Is there any evidence suggesting that the combination of etrumadenant and zimberelimab is likely to be safe for humans?

Research shows that the combination of etrumadenant and zimberelimab is under study for safety in treating advanced dedifferentiated liposarcoma (DDLS). In other research, etrumadenant was tested in patients with advanced colorectal cancer, and no major safety issues emerged, suggesting it might be well-tolerated.

Zimberelimab is a drug that helps the immune system attack cancer cells. While side effects like tiredness or skin reactions can occur, they are usually manageable.

Since this trial is in a later stage, earlier studies found the treatment generally safe enough to continue. This suggests the drug combination is considered safe enough for further research, but side effects will still be monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Etrumadenant and Zimberelimab for treating Dedifferentiated Liposarcoma (DDLPS) because these drugs offer a novel approach compared to current options like surgery, radiation, and chemotherapy. Etrumadenant stands out by targeting the adenosine A2A receptor, which may help to enhance the body’s immune response against tumor cells. Zimberelimab, on the other hand, is a PD-1 inhibitor that helps the immune system recognize and attack cancer cells more effectively. This combination could lead to improved outcomes by boosting the immune system's ability to fight cancer in ways that traditional treatments do not.

What evidence suggests that the combination of etrumadenant and zimberelimab might be an effective treatment for advanced dedifferentiated liposarcoma?

Research has shown that combining etrumadenant and zimberelimab may help treat advanced dedifferentiated liposarcoma (DDLS). In this trial, participants will receive etrumadenant, which blocks a pathway that allows cancer cells to evade the immune system, and zimberelimab, which aids the immune system in identifying and attacking cancer cells. Early results suggest that these drugs together might enhance the body's ability to combat tumors in DDLS. Initial findings from similar studies have demonstrated some positive effects, but further research is needed to confirm these results. ^{1 6 7 8 9}

Who Is on the Research Team?

Sandra D'Angelo, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with advanced dedifferentiated liposarcoma that's inoperable, recurrent, or has spread to other parts of the body can join this trial. They should have tried other treatments without success and be in good health otherwise, with no severe allergies to certain antibodies or active infections like hepatitis or tuberculosis.

Inclusion Criteria

Presence of measurable disease per RECIST v1.1

My condition is an advanced liposarcoma that cannot be surgically removed.

Contraception requirements for female and male participants of reproductive potential

Exclusion Criteria

I have active cancer spread to my brain or spinal cord.

Pregnancy, breastfeeding, planning to become pregnant for female subjects

I am currently being treated for another cancer that is not related.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive etrumadenant and zimberelimab to evaluate effectiveness in advanced Dedifferentiated Liposarcoma

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Etrumadenant
• Zimberelimab

Trial Overview The study is testing a combination of two drugs: Etrumadenant and Zimberelimab. It aims to see if they work together as an effective treatment for this type of sarcoma. Participants will receive both medications and their effects on the cancer will be monitored.

How Is the Trial Designed?

Group I: Participants With Dedifferentiated Liposarcoma/DDLPS Experimental Treatment 2 Interventions

Participants will have a diagnosis of recurrent or metastatic Dedifferentiated Liposarcoma/DDLPS

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a phase 2 study involving 86 patients with advanced soft-tissue or bone sarcoma, pembrolizumab demonstrated some efficacy, particularly in undifferentiated pleomorphic sarcoma (40% response rate) and dedifferentiated liposarcoma (20% response rate), although the overall response rate did not meet the primary endpoint.

The treatment was associated with some serious adverse events, including immune-related conditions like adrenal insufficiency and pneumonitis, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Tawbi, HA., Burgess, M., Bolejack, V., et al.[2022]

In a phase 2 trial involving 62 patients with advanced or metastatic sarcoma, the combination of durvalumab and tremelimumab showed a promising progression-free survival rate of 49% at 12 weeks, indicating its potential efficacy as a treatment option.

While the treatment was generally active, it was associated with some serious adverse events, including one case of grade 5 pneumonitis and colitis, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. Somaiah, N., Conley, AP., Parra, ER., et al.[2023]

Recent advancements in cancer immunotherapy, particularly immune checkpoint inhibitors (ICIs), show promise for improving outcomes in some sarcomas compared to traditional chemotherapy, although most patients still do not respond to these treatments.

The review identifies and evaluates eight potential predictive biomarkers for ICI response in sarcomas, including gene expression signatures and the presence of tertiary lymphoid structures, which could help tailor treatments and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation? Yiong, CS., Lin, TP., Lim, VY., et al.[2023]

In a phase 2 study involving 85 patients with metastatic sarcoma, the combination of nivolumab and ipilimumab showed a higher confirmed response rate (16%) compared to nivolumab alone (5%), indicating that the combination therapy may be more effective for certain sarcoma subtypes.

While both treatments had manageable safety profiles, serious treatment-related adverse events occurred in 19% of patients receiving nivolumab and 26% in those receiving the combination therapy, suggesting that while the combination is promising, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. D'Angelo, SP., Mahoney, MR., Van Tine, BA., et al.[2021]

Patients with metastatic sarcomas have a poor prognosis, with a median overall survival of less than 18 months despite standard chemotherapy regimens, highlighting the need for improved treatment strategies.

The ongoing SUCCEED trial is investigating the efficacy of the mTOR inhibitor ridaforolimus as a potential maintenance therapy to enhance progression-free and overall survival in patients with advanced bone and soft-tissue sarcomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A role for maintenance therapy in managing sarcoma. Ray-Coquard, I., Le Cesne, A.[2021]

Recent advances in immunotherapy for sarcoma show promising results, indicating a potential shift in treatment paradigms, although past attempts have not significantly changed patient outcomes.

To effectively implement immunotherapy on a larger scale, well-designed multi-institutional clinical trials and ongoing laboratory research are essential to understand the unique immunological features of different sarcoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic Intervention against Sarcomas. Pedrazzoli, P., Secondino, S., Perfetti, V., et al.[2021]

In a study of 84 patients with advanced sarcomas treated with off-label anti-PD1 immunotherapy, those with cutaneous primary tumors showed a significantly higher clinical benefit rate of 58%, compared to 11% for non-cutaneous tumors, indicating that tumor location is a key factor in treatment efficacy.

Patients with cutaneous sarcomas also experienced longer progression-free survival (8.6 months vs. 2.5 months) and overall survival (19.0 months vs. 9.2 months), suggesting that cutaneous primary site is a stronger predictor of response to immunotherapy than histological subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? Miao, R., Swank, J., Melzer, D., et al.[2023]

The patient-derived orthotopic xenograft (PDOX) model has been successfully established for sarcoma, allowing researchers to test and identify effective treatments tailored to individual patients.

Despite the limited success of immune and targeted therapies in sarcoma, the PDOX model has shown promise in discovering both approved drugs and experimental therapies that could improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-derived orthotopic xenograft models of sarcoma. Igarashi, K., Kawaguchi, K., Murakami, T., et al.[2020]

Citations

1. clinconnect.io clinconnect.io/trials/NCT05886634

A Study of Etrumadenant and Zimberelimab in People With This clinical trial is studying the effectiveness of a combination of two drugs, etrumadenant and zimberelimab, in treating advanced dedifferentiated ...

2. withpower.com withpower.com/trial/phase-2-sarcoma-4-2023-234ff

Etrumadenant + Zimberelimab for Sarcoma This trial is testing a combination of two drugs, etrumadenant and zimberelimab, to treat patients with advanced dedifferentiated liposarcoma (DDLS).

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-04691

Etrumadenant and Zimberelimab for Treatment in Patients ... This phase II trial tests how well etrumadenant and zimberelimab work in treating patients with dedifferentiated liposarcoma that has come back after a period ...

4. delta.larvol.com delta.larvol.com/Products/?ProductId=0e111ccb-2591-453c-b9fc-7b5d364e2575

etrumadenant (AB928) / Arcus Biosci, Otsuka A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma (clinicaltrials.gov) - P2 | N=16 | Active, not recruiting | Sponsor ...

5. liposarcomasupport.org liposarcomasupport.org/clinical-trials/

Liposarcoma Clinical Trials - LSN ... STUDY: NCT04967521. A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma. Locations: Memorial Sloan Kettering at Basking Ridge ...

6. veri.larvol.com veri.larvol.com/news/etrumadenant-ab928/drug

News - etrumadenant (AB928) An open label study evaluating the efficacy and safety of etrumadenant (AB928) based treatment combinations in participants with metastatic colorectal cancer.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11668776/

Targeting liposarcoma: unveiling molecular pathways and ... In the present review, we focus on the molecular characteristics, molecular diagnostics, driver genes, and molecular mechanisms of liposarcoma.

8. ascopubs.org ascopubs.org/doi/10.1200/EDBK_432234

Immunotherapy in Sarcoma: Current Data and Promising ... We review the current evidence for immunotherapy use in bone sarcomas (BS) and soft tissue sarcomas (STS), with immune checkpoint inhibitors (ICI) and adoptive ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT04791839

Study Details | NCT04791839 | Safety and Efficacy of ... A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zimberelimab, domvanalimab, etrumadenant, or other agents ...