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

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, etrumadenant and zimberelimab, to treat patients with advanced dedifferentiated liposarcoma (DDLS). These patients have cancer that has come back, spread, or cannot be removed by surgery. Etrumadenant stops cancer cells from growing, while zimberelimab helps the immune system fight the cancer.

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.

What data supports the effectiveness of the drugs Etrumadenant and Zimberelimab for treating sarcoma?

The research highlights that immunotherapy, which includes drugs targeting PD-1 and CTLA-4 like nivolumab and ipilimumab, shows promise in treating sarcomas. Etrumadenant and Zimberelimab, which also target similar pathways, may offer potential benefits based on these findings. ^{1 2 3 4 5}

How is the drug combination of Etrumadenant and Zimberelimab unique for treating sarcoma?

Etrumadenant and Zimberelimab are unique because they combine two different types of immune checkpoint inhibitors, which are drugs that help the immune system recognize and attack cancer cells. This combination targets different pathways in the immune system, potentially offering a new approach for treating sarcomas, which have limited treatment options. ^{1 2 6 7 8}

Research Team

Evan Rosenbaum, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]

2. England 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. [2021]

3. England 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. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Immunotherapeutic Intervention against Sarcomas. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

A role for maintenance therapy in managing sarcoma. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? [2023]

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

Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation? [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Patient-derived orthotopic xenograft models of sarcoma. [2020]