Symptoms and General Pathology

All Conditions

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Skin and Connective Tissue Diseases

Rare Diseases

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Osteosarcoma

Sarcoma

Liposarcoma

Hemangiosarcoma

Disease Attributes

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Adipose Tissue

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immunologic Factors

Patients receive oleclumab IV over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Oleclumab

Neeta Somaiah

This phase II trial investigates how well oleclumab and durvalumab work in treating patients with sarcoma that has come back (recurrent) or does not respond to treatment (refractory) or has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as oleclumab and durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To estimate the tumor response (Response Evaluation Criteria in Solid Tumors \[RECIST\]) at 4 months in patients with relapsed/refractory sarcoma. (Cohorts 1 and 2) II. To determine the event-free survival (EFS) rate at 4 months after initiation of the treatment in patients with relapsed/refractory osteosarcoma receiving novel immunotherapeutic agents. (Cohort 3)

SECONDARY OBJECTIVES:

I. To determine the progression-free survival (PFS) rate at 12 weeks after initiation of the treatment in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.

II. To estimate the tumor response (Immune-related Response Criteria \[irRC\] and RECIST) in patients with relapsed/refractory sarcoma.

III. To evaluate the safety and tolerability of receiving novel immunotherapeutic agents in patients with relapsed/refractory sarcoma.

IV. To estimate the median PFS and overall survival (OS) in patients with relapsed/refractory sarcoma receiving novel immunotherapeutic agents.

EXPLORATORY OBJECTIVES:

I. To determine expression of biomarkers (including but not limited to CD73, PD-1 and PD-L1) in pre \& post treatment (tx) samples.

II. Quantification and characterization of the immune infiltrate (and other histologic and immunohistologic changes) from tissue samples prior to treatment initiation and post treatment (biopsy at week 6).

III. Identification/quantification of immunologic changes (CD4+, CD8+, Teff, Treg cells and NK cells) in peripheral blood.

IV. Determining an immunoscore based on baseline tumor sample (identification of molecular response/resistance patterns/future therapy options).

OUTLINE:

Patients receive oleclumab intravenously (IV) over 1 hour every 2 weeks for 5 doses, then every 4 weeks thereafter. Patients also receive durvalumab IV over 1 hour every 4 weeks. Cycle repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, and then every 3 months for up to 5 years.

Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma

A Phase II Multi-Arm Study to Test the Efficacy of Oleclumab and Durvalumab in Multiple Sarcoma Subtypes

Evaluated using immunohistochemistry (CD73, PD-1/PD-L1) expression analysis). Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/analysis of variance (ANOVA) or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Evaluated using immunofluorescence analysis. Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/ANOVA or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Evaluated using flow cytometry analysis. Exploratory data analysis and graphical methods will be applied to examine the distribution of the biomarker data, error checking, and outlier identification. T-test/ANOVA or their nonparametric counterparts, Wilcoxon rank-sum test/Kruskal-Wallis test will be used to detect differences of the biomarkers between groups. Linear mixed effect models for repeated measures analysis (Liang, 1986) will be employed to assess the change in biomarkers over time with multi-covariates including disease characteristics (tumor stage, site, pathology), and other prognostic factors. Appropriate transformation of the outcome assessment values will be used to satisfy the normality assumption of linear mixed effect model.

Defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Defined as the time from enrollment to disease progression, death, or discontinuation of treatment for any reason (for example toxicity, patient preference, or initiation of new treatment without documented disease progression). Defined by RECIST 1.1. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

Defined as the time from treatment onset to either disease progression as defined by RECIST 1.1. Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

Defined by Immune-related Response Criteria (irRC) and RECIST.

Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity data by grade and relationship with the treatment by cohorts and 3 cohorts combined, will be summarized by frequency tables. For the toxicity endpoint, per-treated analysis will be used to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received. Toxicity rate will be estimated with 95% confidence interval.

Will be estimated using the Kaplan-Meier method. Log-rank test will be performed to test the difference in survival between groups. Regression analysis of survival data based on the Cox proportional hazards model will be conducted. The proportional hazards assumption will be evaluated graphically and analytically, and regression diagnostics (e.g., martingale and Shoenfeld residuals) will be examined to ensure the models are appropriate.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Adenosine

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

Will be administered PO daily for 24 weeks

Etrumadenant

Will be administered IV every 2 weeks for 24 weeks

Zimberelimab

Evan Rosenbaum, MD

Sujana Movva, MD

William Tap, MD

Participants will have a diagnosis of dedifferentiated liposarcoma (DDLS) that has spread beyond its original location (advanced). In addition, their DDLS either has come back after treatment (recurrent), has spread to different parts of your body (metastatic), or is unable to be removed surgically (unresectable). The purpose of this study is to find out whether the combination of etrumadenant and zimberelimab is an effective treatment for people with advanced DDLS.

A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma

A Phase II Study of Adenosine Receptor (A2A and A2B) Inhibition (AB928) in Combination With Anti-PD-1 Therapy (AB122) in Patients With Advanced Dedifferentiated Liposarcoma

To estimate the overall response rate (CR + PR per RECIST 1.1) to etrumadenant combined with zimberelimab at 24 weeks in patients with advanced Dedifferentiated Liposarcoma/DDLPS

Memorial Sloan Kettering Cancer Center

Cemiplimab

Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive palbociclib PO on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Patients receive palbociclib PO and cemiplimab IV on study. Patients undergo MRI or a CT scan throughout the trial. Patients may also undergo blood sample collection on study.

Magnetic Resonance Imaging

Computed Tomography

Biospecimen collection

Questionnaire Administration

Matthew Ingham, MD

Beth Smith

Site Public Contact

Vanessa Eulo

Shahzad Siddique

Steven I. Robinson

Tatjana Kolevska

Sosipatros A. Boikos

Tanmay Sahai

Bryan A. Faller

Pedro Viveiros

Bruce E. Brockstein

This phase II trial compares the effect of treatment with palbociclib alone to treatment with palbociclib plus cemiplimab for treating patients with dedifferentiated liposarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cemiplimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

PRIMARY OBJECTIVES:

I. To perform a safety lead-in among 6 patients to confirm that the combination of palbociclib and cemiplimab is safe and tolerable.

II. To evaluate whether palbociclib in combination with cemiplimab (Arm 2) demonstrates a superior progression-free survival (PFS) compared to palbociclib monotherapy (Arm 1) for patients with advanced dedifferentiated liposarcoma (DDLPS).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile in and across each treatment arm as determined by both Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE criteria.

II. To evaluate and compare the objective response rate (ORR) and duration of response (DOR) in and across each treatment arm.

III. To evaluate and compare the overall survival (OS) in and across each treatment arm.

IV. To evaluate and compare progression-free rate at 8 weeks (PFR8) in and across each treatment arm.

EXPLORATORY OBJECTIVES:

I. To collect genomic sequencing data previously collected as standard of care, including data on CDK4 copy number (as determined by fluorescence in situ hybridization \[FISH\] or other molecular testing).

II. To conduct multiplex immunohistochemistry using archival tumor tissue (where available) to define densities of infiltrating immune cell subsets and tumor and immune cell major histocompatibility complex (MHC) and PD-L1 expression.

III. To perform an exploratory analysis to evaluate for any relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment.

IV. To explore efficacy and toxicity endpoints, including PFS and ORR, for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive palbociclib orally (PO) on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans throughout the trial. Patients may also undergo blood sample collection on study.

ARM II: Patients receive palbociclib PO and cemiplimab intravenously (IV) on study. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma

Official Title A Randomized Phase 2 Trial With a Safety Lead-In to Evaluate Palbociclib Versus Palbociclib and Cemiplimab for the Treatment of Advanced Dedifferentiated Liposarcoma

Explore data on CDK4 copy number (by fluorescence in situ hybridization \[FISH\] or other molecular testing) through plots and summary statistics.

Conduct multiplex immunohistochemistry using archival tumor tissue (where available) to summarize densities of infiltrating immune cell subsets and tumor and immune cell MHC and PD-L1 expression.

Explore the relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment Clinical endpoints include PFS, objective response rate, OS, PFR8, and DoR. Cox regression will be used on time-to-event outcomes and T-test on binary outcomes

Explore the efficacy and toxicity endpoints for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination A sensitivity analysis will be conducted to see how crossover effects overall survival. Rate and severity of adverse events will be used to assess differences between crossover and non-crossover patients.

Efficacy analyses will be based on intention to treat principles. PFS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 12, 24, 36, and 48 months will be estimated along with corresponding 95% confidence intervals. A log-rank test will be used to compare the PFS distributions between the two treatment arms in this cohort. Cox proportional hazards models will also be used to assess the impact of treatment arm on PFS when stratifying on the stratification factors.

Patients will be evaluated for adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. Summary statistics (e.g., mean, median, standard deviation) and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in the treatment arm will be compared to the control arm with chi-squared tests (or suitable alternative) used for comparisons where applicable. Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.

Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.

Defined as the time from randomization to death due to any cause. Patients who are alive will be censored at last follow-up for OS. The distribution of survival time will be estimated using the method of Kaplan-Meier. OS will be compared between treatment arms using the log-rank test. OS medians, survival rates and hazard ratio will be estimated along with 95% confidence intervals.

Defined as the proportion of evaluable patients who are alive and without evidence of disease progression 8 weeks after initiation of study therapy. The final PFR8 point estimate and corresponding 95% confidence interval calculated using Clopper-Pearson method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oleclumab and Durvalumab for the Treatment of Recurrent, Refractory, or Metastatic Sarcoma	NCT04668300	Metastatic Angi... Metastatic Dedi... Metastatic Oste... Recurrent Angio... Recurrent Dedif... Recurrent Osteo... Refractory Dedi... Refractory Oste...	Durvalumab Oleclumab	12 Years -	M.D. Anderson Cancer Center
A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma	NCT05886634	Dedifferentiate... Soft Tissue Sar... Sarcoma,Soft Ti... Sarcoma Recurrent Dedif... Unresectable De... Metastatic Dedi...	Etrumadenant Zimberelimab	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of Etrumadenant and Zimberelimab in People With Dedifferentiated Liposarcoma	NCT05886634	Dedifferentiate... Soft Tissue Sar... Sarcoma,Soft Ti... Sarcoma Recurrent Dedif... Unresectable De... Metastatic Dedi...	Etrumadenant Zimberelimab	18 Years -	Memorial Sloan Kettering Cancer Center
Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma	NCT05694871	Advanced Dediff... Locally Advance... Metastatic Dedi... Stage III Soft ... Stage IV Soft T... Unresectable De...	Palbociclib Cemiplimab Magnetic Resona... Computed Tomogr... Biospecimen col... Questionnaire A...	18 Years -	Alliance for Clinical Trials in Oncology

Spots Global Cancer Trial Database for metastatic dedifferentiated liposarcoma