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

NCT04668300 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: 2020-0159NCI-2020-05660P30CA016672
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Angiosarcoma; Metastatic Dedifferentiated Liposarcoma; Metastatic Osteosarcoma; Recurrent Angiosarcoma; Recurrent Dedifferentiated Liposarcoma; Recurrent Osteosarcoma; Refractory Dedifferentiated Liposarcoma; Refractory Osteosarcoma

Outcome Measures

Primary Outcomes (2)

• Response rate (Cohorts 1 and 2)

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

  At 4 months post treatment initiation

• Event-free survival (Cohort 3)

  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.

  At 4 months

Secondary Outcomes (5)

• Progression-free survival (PFS)

  At 12 weeks

• Response rate (CR, PR)

  Up to 5 years

• Incidence of adverse events (immune-related grade 3 and/or 4 toxicity)per treatment cohort

  Up to 5 years

• PFS

  Up to 24 weeks

• Overall survival

  Up to 5 years

Other Outcomes (3)

• Biomarker (CD73, PD-1/PD-L1) expression analysis (pre & post treatment tissue samples)

  Up to 5 years

• Tumor infiltrating lymphocytes (pre and post treatment tissue samples)

  Up to 5 years

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

  Up to 5 years

Study Arms (1)

Treatment (oleclumab, durvalumab)

EXPERIMENTAL

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.

Biological: Durvalumab; Biological: Oleclumab

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (oleclumab, durvalumab)

Oleclumab BIOLOGICAL

Given IV

Also known as: Anti-CD73 Monoclonal Antibody MEDI9447, MEDI9447

Treatment (oleclumab, durvalumab)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 years of age or older (cohort 1 and cohort 2); 12 years of age or older (cohort 3)
• Histologically or cytologically confirmed sarcoma that fall into one of the following categories. Patients with low-grade tumors are eligible if there is definite evidence of metastasis or progression
• Angiosarcoma
• Dedifferentiated liposarcoma
• Osteosarcoma
• Must have received and have progressed, are refractory or intolerant to standard therapy appropriate for the specific sarcoma subtype, if there is a standard therapy for the subtype
• Subjects must have at least 1 lesion that is measurable by RECIST
• A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST, and has clearly progressed since radiation
• Subjects undergoing fresh tumor biopsies must have additional non-target lesions that can be biopsied at acceptable risk as judged by the investigator or if no other lesions suitable for biopsy, then a RECIST target lesion used for biopsy must be \>= 2 cm in longest diameter
• Subjected must consent to provide archived tumor specimens for correlative biomarker studies. Tumor tissue must be identified and availability confirmed prior to initiation of study therapy. In the setting where archival material is unavailable or unsuitable for use, or there have been multiple intervening therapies subjects must consent and undergo fresh tumor biopsy. A tumor lesion planned for biopsy must not have a RECIST target lesion unless there are no other lesions suitable for biopsy and lesions used for biopsy is \>= 2 cm in longest diameter
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (use Karnofsky for patients \> 16 years and Lansky for patients =\< 16)
• Absolute neutrophil count \>= 1.5 x 10\^9/L (1,500/mm\^3) (without growth factor within 28 days of first dose or transfusion within 14 days of first dose support)
• Platelet count \>= 100 x 10\^9/L (100,000/mm\^3) (without growth factor within 28 days of first dose or transfusion within 14 days of first dose support)
• Hemoglobin \>= 9.0 g/dL (without growth factor within 28 days of first dose or transfusion within 14 days of first dose support)
• Calculated creatinine clearance (CrCl) or 24-hour urine CrCl \> 40 mL/min Cockcroft-Gault formula (using actual body weight) will be used to calculate CrCl

You may not qualify if:

• Prior therapy with anti-PD1, anti-PD-L1 (including durvalumab) or anti-CD73
• Active or prior documented autoimmune disease (including inflammatory bowel disease, celiac disease, Wegener syndrome) within the past 2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
• Untreated central nervous system metastatic disease, leptomeningeal disease, or cord compression. Subjects previously treated central nervous system metastases that are radiographically and neurologically stable for at least 28 days and do not require corticosteroids (or any dose) for symptomatic management for at least 14 days prior to first dose of durvalumab and oleclumab are permitted to enroll
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Receipt of any conventional or investigational anticancer therapy within 21 days prior to the first dose of study drug
• Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. In addition, local treatment (e.g., by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the first cycle with prior consultation and in agreement with the principal investigator (PI)
• Current or prior use of immunosuppressive medication within 14 days prior to the first of durvalumab or oleclumab. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication)
• History of primary immunodeficiency, solid organ transplantation, or previous clinical diagnosis of tuberculosis
• True positive test results for human immunodeficiency virus (HIV) or hepatitis B or hepatitis C
• Receipt of live, attenuated vaccine within 30 days prior to the first dose of investigational products (NOTE: Subjects, if enrolled, should not receive live vaccine during the study and 180 days after the last dose of investigational products)
• Major surgery (as defined by the investigator) within 4 weeks or thoracotomy for pulmonary metastases within 2 weeks prior to first dose of treatment or if still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable
• Other invasive malignancy, within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Hemangiosarcoma; Liposarcoma; Osteosarcoma

Interventions

durvalumab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Neoplasms, Adipose Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Neeta Somaiah

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2020
• First Posted: December 16, 2020
• Study Start: November 26, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)