Etrumadenant + Zimberelimab for Sarcoma
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
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.
12345How 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.
12678Eligibility 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
+9 more
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.
+17 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Participants With Dedifferentiated Liposarcoma/DDLPSExperimental Treatment2 Interventions
Participants will have a diagnosis of recurrent or metastatic Dedifferentiated Liposarcoma/DDLPS
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)Montvale, NJ
Memorial Sloan Kettering Westchester (Limited Protocol Activities)Harrison, NY
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)Basking Ridge, NJ
Memorial Sloan Kettering Nassau (Limited protocol activities)Rockville Centre, NY
More Trial Locations
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Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. [2023]Few standard treatment options are available for patients with metastatic sarcomas. We did this trial to evaluate the efficacy, safety, and changes in the tumour microenvironment for durvalumab, an anti-PD-L1 drug, and tremelimumab, an anti-CTLA-4 drug, across multiple sarcoma subtypes.
Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. [2021]Patients with metastatic sarcoma have limited treatment options. Nivolumab and ipilimumab are monoclonal antibodies targeting PD-1 and CTLA-4, respectively. We investigated the activity and safety of nivolumab alone or in combination with ipilimumab in patients with locally advanced, unresectable, or metastatic sarcoma.
Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. [2022]Patients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. Chemotherapy and targeted therapies offer short-lived disease control. We assessed pembrolizumab, an anti-PD-1 antibody, for safety and activity in patients with advanced soft-tissue sarcoma or bone sarcoma.
Immunotherapeutic Intervention against Sarcomas. [2021]Advances in systemic therapy for sarcoma have produced, over the last two decades, relatively short-term benefits for the majority of patient. Among the novel biologic therapeutics that will likely increase our ability to cure human cancer in the years to come, immunotherapy is one of the most promising approaches. While past attempts to use immunotherapy have failed to dramatically shift the paradigm of care for the treatment of patients with sarcoma, major advances in basic and translational research have resulted, in more recent years, in clinical trial activity that is now beginning to generate promising results. However, to move from "proof of principle" to large scale clinical applicability, we need well-designed, multi-institutional clinical trials, along with continuous laboratory research to explore further the immunological characteristics of individual sarcoma subtypes and the consequent tailoring of therapy.
A role for maintenance therapy in managing sarcoma. [2021]Despite the use of recommended chemotherapy regimens, patients with metastatic sarcomas have a poor prognosis. To date, the median overall survival for metastatic disease remains less than 18 months. First-line treatment of most metastatic sarcomas consists of chemotherapy with or without surgical excision of residual disease, followed by "watchful waiting" until disease progression or recurrence. According to the current treatment paradigm, recommended by United States and European clinical guidelines, chemotherapy is administered for a fixed number of cycles, and then a watchful waiting approach is taken once a best response is achieved. Single-agent doxorubicin remains the standard for treatment of most soft-tissue sarcomas (STS), as combination and dose-intense regimens have largely failed to improve survival. Combination chemotherapy is the standard treatment approach for osteosarcoma and Ewing's sarcoma, but outcomes are poor for patients with recurrent disease. In order to improve outcomes (in particular, progression-free survival [PFS] and overall survival [OS]), strategies shown to be effective in other solid malignancies, such as maintenance therapy and long-term treatment with targeted therapy, are being investigated in patients with advanced sarcomas. One potential promising approach is the use of mammalian target of rapamycin (mTOR) inhibitors for maintenance therapy. One such mTOR inhibitor, ridaforolimus (AP23573, MK-8669), is currently being evaluated in patients with advanced bone and STS in the ongoing Sarcoma mUlti-Center Clinical Evaluation of the Efficacy of riDaforolimus (SUCCEED) trial.
Anti-PD-1 therapy in advanced sarcomas: is cutaneous primary site a stronger predictor of response than histologic subtype? [2023]Immune checkpoint inhibitors (ICIs) have shown modest antitumor activity in unselected advanced sarcomas. Histology driven approach to patient selection is the current standard for off-label anti-programmed cell death 1 (PD1) immunotherapy use.
Biomarkers for immune checkpoint inhibition in sarcomas - are we close to clinical implementation? [2023]Sarcomas are a group of diverse and complex cancers of mesenchymal origin that remains poorly understood. Recent developments in cancer immunotherapy have demonstrated a potential for better outcomes with immune checkpoint inhibition in some sarcomas compared to conventional chemotherapy. Immune checkpoint inhibitors (ICIs) are key agents in cancer immunotherapy, demonstrating improved outcomes in many tumor types. However, most patients with sarcoma do not benefit from treatment, highlighting the need for identification and development of predictive biomarkers for response to ICIs. In this review, we first discuss United States (US) Food and Drug Administration (FDA)-approved and European Medicines Agency (EMA)-approved biomarkers, as well as the limitations of their use in sarcomas. We then review eight potential predictive biomarkers and rationalize their utility in sarcomas. These include gene expression signatures (GES), circulating neutrophil-to-lymphocyte ratio (NLR), indoleamine 2,3-dioxygenase (IDO), lymphocyte activation gene 3 (LAG-3), T cell immunoglobin and mucin domain-containing protein 3 (TIM-3), TP53 mutation status, B cells, and tertiary lymphoid structures (TLS). Finally, we discuss the potential for TLS as both a predictive and prognostic biomarker for ICI response in sarcomas to be implemented in the clinic.
Patient-derived orthotopic xenograft models of sarcoma. [2020]Sarcoma is a rare and recalcitrant malignancy. Although immune and novel targeted therapies have been tested on many cancer types, few sarcoma patients have had durable responses with such therapy. Doxorubicin and cisplatinum are still first-line chemotherapy after four decades. Our laboratory has established the patient-derived orthotopic xenograft (PDOX) model using surgical orthotopic implantation (SOI). Many promising results have been obtained using the sarcoma PDOX model for identifying effective approved drugs and experimental therapeutics, as well as combinations of them for individual patients. In this review, we present our laboratory's experience with PDOX models of sarcoma, and the ability of the PDOX models to identify effective approved agents, as well as experimental therapeutics.