Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas

This study is testing a combination of medicines for people with certain types of sarcoma, including Malignant Peripheral Nerve Sheath Tumor (MPNST) and those with Neurofibromatosis type 1 (NF1). The medicines being studied are Selumetinib, ZEN-3694, and Durvalumab. Researchers want to see how safe these combinations are and if they help patients. The study is open to adults aged 18 to 99 years old who have specific types of sarcoma that are difficult to treat or cannot be removed by surgery. The study is currently recruiting patients.

Study design: This is an open-label (meaning you and your doctors will know what treatments you are receiving) Phase 1/2 study. It plans to enroll 41 participants and will test different combinations of the study drugs.
What's involved: The study will measure safety and tolerability from the first dose through the end of the first treatment cycle (up to 28 days). Clinical benefit will be measured from the first dose through completion of 4 treatment cycles (up to 112 days).
Compensation: Not stated in the trial record.
Follow-up: Not specified.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas

Recruiting

PHASE2Ages 18–99InterventionalTreatment

University of Alabama at Birmingham

~41 participants

Updated 2026-08-24 on ClinicalTrials.gov

What's tested:Selumetinib + ZEN-3694 ± Durvalumab

At a glance

Recruiting sites

1 of 1 listed site is recruiting right now

RecruitingSuspended, closed, or not yet open

What they're measuring

Part A: Safety and Tolerability Selumetinib with ZEN-3694

Measured over From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).

+2 more outcomes measured

Conditions

MPNST

NF1

Sarcoma

Where it's being run

1 sites across 1 states

Alabama1

Who to contact

Girish Dhall, MD

[email protected]

205.638.6259

Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

MFH/ undifferentiated pleomorphic sarcoma

Unclassified sarcoma

Rhabdomyosarcoma

Malignant peripheral nerve sheath tumor (MPNST)

Osteosarcoma

Ewing or Ewing-like sarcoma

Synovial sarcoma

Desmoplastic small round blue cell tumor (DSRCT)

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering on this study excluding chronic grade 1 toxicities and alopecia.

No limitation on the number of prior chemotherapy regimens that the patient may have received prior to study entry.

Myelosuppressive chemotherapy: The last dose of all myelosuppressive anticancer drugs must be at least 3 weeks (≥21 days) and 42 days if prior nitrosourea prior to study entry.

Immunotherapy: The last dose of immunotherapy (monoclonal antibody or vaccine) must be at least 4 weeks prior to study entry.

Biologic (anti-cancer agent): The last dose of all biologic agents for the treatment of the patient's cancer (such as retinoids or tyrosine kinase inhibitors) must be at least 7 days prior to study entry. Prior therapy with a MEK, Ras, or Raf inhibitor used for treatment of malignant sarcoma is not allowed. Prior therapy of MEK, Ras, or Raf inhibitor for other tumor such as plexiform neurofibroma or glioma is allowed.

Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study

Radiation therapy: The last dose of radiation to more than 25% of marrow containing bones (pelvis, spine, skull) must be at least 4 weeks prior to study entry. The last dose of all other local palliative (limited port) radiation must be at least 2 weeks prior to study entry.

Stem Cell Transplantation. At least 2 months post-autologous stem cell transplant.

Growth Factors. The last dose of colony stimulating factors, such as filgrastim, sargramostim, and erythropoietin, must be at least 1 week prior to study entry, the last dose of long-acting colony stimulating factors, such as pegfilgrastim, must be at least 2 weeks prior to study entry.

Karnofsky performance level ≥ 50% (See Appendix II).

Patients who are unable to walk because of paralysis or motor weakness, but who are able to use a wheelchair will be considered ambulatory for the purpose of calculating the performance score.

Peripheral absolute neutrophil count (ANC) of ≥1000/µL

Platelet count ≥100,000/µL (transfusion independent (no transfusion within at least 7 days prior to enrollment))

Total bilirubin must be ≤ 1.5 times the upper limit of normal (ULN)

SGOT (AST)/SGPT (ALT) must be ≤ 3.0 times ULN unless liver metastases are present, in which case it must be ≤ 5x ULN

Normal ejection fraction (ECHO or cardiac MRI) ≥53% (or the institutional normal; if a range is given then the upper value of the range will be used)

QTC or QTcF ≤ 450msec

Have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (but not tubal ligation)

Have medically confirmed, irreversible premature ovarian failure.

Use of medroxyprogesterone acetate depot injection (Depo-proveraTM). (Please note: use of any other oral, injected, or implanted hormonal methods of contraception cannot be considered highly effective as it is currently unknown whether investigational agents may reduce their effectiveness)

Placement of a copper-banded intrauterine device (IUD) or intrauterine system (IUS)

Bilateral tubal ligation

Vasectomized partner

Exclusion

A malignancy treated with curative intent and with no known active disease ≥5 years prior to study entry

Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease

Adequately treated carcinoma in situ without evidence of disease

Stable optic pathway glioma or low grade glioma not receiving active therapy

Severely impaired lung function defined as spirometry and DLCO that is 50%of the normal predicted value corrected for hemoglobin and alveolar volume and/or O2 saturation that is 88% or less at rest on room air. For patients who do NOT have respiratory symptoms (e.g., dyspnea at rest, known requirement for supplemental oxygen), pulmonary function test is not required.

Cardiac conditions as follows:

Uncontrolled hypertension (blood pressure ≥150/95 mmHg despite medical therapy.

Acute coronary syndrome within 6 months prior to starting drug therapy

Uncontrolled angina despite medical therapy (Canadian Cardiovascular Society grade II-IV despite medical therapy

Symptomatic heart failure NYHA Class II-IV prior or current cardiomyopathy or severe valvular disease

Prior or current cardiomyopathy including but not limited to the following: Known hypertrophic cardiomyopathy; Known arrhythmogenic right ventricular cardiomyopathy; or Previous moderate or severe impairment of left ventricular systolic function (LVEF \<45% on echocardiography or equivalent of MUGA) even if full recovery has occurred

Atrial fibrillation with a ventricular rate of \>100 beats per minute on ECG at rest

Uncontrolled infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Active primary immunodeficiency

Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome, or renal tubular acidosis.

Current gastrointestinal conditions such as refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of small bowel, symptomatic inflammatory bowel disease, or ulcerative colitis, or partial or complete bowel obstruction.

Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (colitis, Crohn's), celiac disease, systemic lupus erythematosus, Wegener syndrome, myasthenia gravis, Graves' disease, rheumatoid arthritis, uveitis.

Patients with vitiligo or alopecia

Patients with hypothyroidism (e.g., following Hashimoto's syndrome) stable on hormone replacement

Psoriasis that does not require systemic therapy

Patients with celiac disease that is controlled by diet alone

Current or past history of retinal vein occlusion

Known intraocular pressure (IOP)\>21 mmHg (or ULN adjusted by age) or uncontrolled glaucoma.

Subjects with ophthalmological findings secondary to long standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) or long standing orbito-temporal PN (such as vision loss, strabismus) will not be considered a significant abnormality for purposes of this study.

What this trial measures

Part A: Safety and Tolerability Selumetinib with ZEN-3694From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).
To determine the safety, tolerability, and recommended doses of selumetinib given in combination with ZEN-3694 in participants with refractory sarcomas including MPNST. The Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of selumetinib in combination with ZEN-3694 will be determined based on dose-limiting toxicities (DLTs) observed during the first cycle of therapy. DLTs are defined as grade ≥3 toxicities attributable to the study drugs, assessed according to CTCAE v5. Dose escalation will proceed in cohorts of 3-6 participants, with possible dose de-escalation if ≥33% of participants experience a DLT. At the RP2D, the cohort may be expanded to up to six additional participants to further evaluate pharmacokinetics and tolerability.
Part B: Safety and Tolerability of Durvalumab with Combination of Selumetinib and ZEN-3694From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).
To determine the safety, tolerability, and recommended doses of durvalumab when given in combination with selumetinib and ZEN-3694 in participants with refractory sarcomas including MPNST. The Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of the combination of selumetinib, ZEN-3694, and durvalumab will be determined based on dose-limiting toxicities (DLTs) observed during the first cycle of therapy. DLTs are defined as grade ≥3 toxicities attributable to the study drugs, assessed according to CTCAE v5. Dose escalation will proceed in cohorts of 3-6 participants, with possible dose de-escalation if ≥33% of participants experience a DLT. At the RP2D, the cohort may be expanded to up to six additional participants to further evaluate pharmacokinetics and tolerability.
Part C: Determine the Clinical Benefit of Selumetinib, ZEN-3694 and DurvalumabFrom first dose through completion of 4 treatment cycles for each participant (up to 112 days).
Clinical benefit rate defined as radiographic complete response, partial response, or stable disease, greater than or equal to four cycles. The primary endpoint is the clinical benefit rate, defined as the proportion of evaluable participants achieving a complete response (CR), partial response (PR), or stable disease (SD) for at least 4 treatment cycles. A Simon's optimal two-stage phase 2 design will be used to evaluate efficacy in participants with unresectable or metastatic NF1-associated MPNST. In the first stage, 9 participants will be enrolled; the trial will stop early if 0 participants respond. If the study continues to the second stage, a total of 17 participants will be enrolled, and the treatment will be considered ineffective if ≤2 participants respond. The target clinical benefit rate is 30% (p1 = 0.30), and a rate ≤5% (p0 = 0.05) is considered uninteresting.

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