MPNSTPhase 2NCT05253131
Trial of Selumetinib and Bromodomain Inhibitor With Durvalumab for Sarcomas
A Phase 2 study testing Selumetinib + ZEN-3694 ± Durvalumab in people with MPNST and NF1, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with ZEN-3694 and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- What is being tested?
- Selumetinib + ZEN-3694 ± Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2026to 15 Nov 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Inclusion Criteria AGE: ≥ 18 years of age Weight: >30 kg Life expectancy of at least 12 weeks
- Part A and B (Phase 1): Patients with histologically confirmed soft tissue or bone sarcoma of the following subtypes:
- MFH/ undifferentiated pleomorphic sarcoma
- Unclassified sarcoma
- Rhabdomyosarcoma
- Malignant peripheral nerve sheath tumor (MPNST)
Show all 96Show fewer
- Osteosarcoma
- Ewing or Ewing-like sarcoma
- Synovial sarcoma
- Desmoplastic small round blue cell tumor (DSRCT)
- Patients must have progressed or demonstrated disease that is refractory to standard therapies.
- Patients for whom no standard of care treatments exist are eligible.
- Part C (Phase 2): Patients with progressive, relapsed, unresectable or metastatic NF associated MPNST.
- MEASURABLE DISEASE:
- Patients must have evaluable or measurable disease (Phase 1) and measurable disease by RECISTv1.1 (Phase 2).
- 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.
- Hemoglobin ≥9.0 g/dL (transfusion permissible)
- 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
- RENAL FUNCTION:
- Serum creatinine ≤ 1.5 times ULN or measured reatinine clearance >50 mL/min or calculated creatinine clearance > 50 mL/min by the Cockcroft- Gault formula (Cockgraft and Gault 1976) or by the 24 hour urine collection for determination of creatinine clearance
- 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
- Fertile men and women of childbearing potential must agree to use an effective method of birth control.
- Female participants of childbearing potential must be willing to practice highly effective contraception as detailed below from the time of screening until 3 months after discontinuing the study.
- They must not be breastfeeding and must have negative pregnancy test prior to start of dosing.
- For a female participant to be considered as of not childbearing potential, she should fulfil one of the following:
- Post-menopausal women, defined as either women aged more than 50 years and have amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments, or, women under 50 years who have amenorrhea for at least 12 months following cessation of exogenous hormonal treatments, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in the postmenopausal range for the institution.
- or
- Have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy (but not tubal ligation)
- Have medically confirmed, irreversible premature ovarian failure.
- Highly effective methods of contraception are:
- 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
- Barrier methods include:
- Occlusive cap (e.g. diaphragm or cervical/vault caps) with spermicide
- Male participants should either be surgically sterile or willing to use an effective barrier method of contraception during the study and for 3 months following the last dose of drug therapy if sexually active with a female of childbearing potential. If not done, storage of sperm prior to receiving drug therapy will be advised to male participants with a desire to have children.
- Male subjects must agree to refrain from sperm donation during and until 90 days from drug therapy discontinuation.
- CNS DISEASE: Patients with central nervous system disease are eligible or enrollment if they have received prior radiotherapy or surgery to sites of CNS metastatic disease and are without evidence of clinical progression or stable disease at 4 weeks.
- Exclusion Criteria:History of another primary malignancy except for
- 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
- History of leptomeningeal carcinomatosis.
- Patients receiving other anti-cancer agents are not eligible.
- Patients who cannot swallow whole pills.
- History of allogeneic organ transplantation.
- Current or prior use of immunosuppressive medications within 14 days prior to study entry. The following are exceptions to this criterion:
- intranasal, inhaled, topical steroids or local steroid injection (e.g., intra-articular injection)
- Systemic corticosteroids used at physiologic doses not to exceed 10mg/day of prednisone or its equivalent.
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
- Patients should not receive immunizations with attenuated live vaccines within four weeks of study entry or during study period.
- Any recent major surgery within a minimum of 4 weeks prior to starting drug therapy. Placement of vascular access device, percutaneous tumor biopsy, or bone marrows are not considered major surgical procedures and no minimum time frame prior to starting study drug.
- Patients who have any known severe and/or uncontrolled medical therapy is required.
- conditions or other conditions that could affect their participation in the study such as:
- 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.
- The following exceptions are:
- 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
- Ophthalmological conditions as follows:
- 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.
- Any Supplementation with vitamin E.
- Hypersensitivity to investigational products, or drugs with similar chemical structures to investigational products.
- Patients unwilling or unable to comply with the protocol.
- While not an exclusion criterion, unless clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medications. In particular, participants should avoid medications that are known to either induce or inhibit the hepatic activity of CYP1A2, CYP2C19, and CYP3A4.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's of Alabama
Birmingham, Alabama, 35294
Girish Dhall, MD, 205.638.6259, gdhall@uab.edu
Manjul Virmani, MSRA, (205) 638-5450, manjulvirmani@uabmc.edu
About this study
Official title: Phase 1/2 Trial of the MEK Inhibitor Selumetinib and Bromodomain Inhibitor ZEN-3694 With Durvalumab (MEDI4736), a PD-L1 Antibody for Sarcomas Including Malignant Peripheral Nerve Sheath Tumors
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with ZEN-3694 and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.
Read the detailed description
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with bromodomain inhibitor (ZEN-3694) and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.
Part A will be a phase 1 dose escalation study of the combination with selumetinib and ZEN-3694.
Part B will be phase 1 study combining the determined dose of selumetinib and ZEN-3694 from Part A with durvalumab.
Part C will be a phase 2 study combining selumetinib, ZEN-3694 with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.
Statistical Plan Phase 1: Conventional dose escalation schema. Cohorts of 3 to 6 participants will be treated per dose level. At the RP2D or last dose level, the cohort may be expanded to up to an additional six participants for further pharmacokinetic and tolerability experience. The MTD/RP2D will be defined as the dose level immediately below the level at which ≥33% of participants in a cohort experience a DLT based on toxicities observed in the first drug therapy cycle.
Phase 2: A Simon's two-stage phase 2 trial of selumetinib, ZEN-3694, and durvalumab to determine the safety and clinical benefit in patients with unresectable or metastatic MPNST Maximum Total Number of Subjects Phase 1: 6-24 participants Phase 2: 9 participants in first stage with additional 8 participants in stage 2.
Target Population Individuals ≥ 18 years of age with relapsed or refractory histologically confirmed sarcoma including MPNST. This may be amended when tolerability is established.
Anticipated Length of Study Maximum enrollment number for entire study is 41participants. It is expected that 15-25 participants will be enrolled per year, and enrollment is expected to be completed in 3 years with follow up after last participant accrual to be approximately 12 months.
- Being tested
- Selumetinib + ZEN-3694 ± Durvalumab
- Keywords
- MPNST, Neurofibromatosis 1, NF1, sarcoma
- Medical subject headings
- Neurofibrosarcoma, Sarcoma, Neurofibromatosis 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selumetinib + ZEN-3694 ± DurvalumabCombination product
Selumetinib and ZEN-3694 administered per protocol, with durvalumab added in later study parts.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 and 2 Study of Selumentinib, ZEN-3694 and Durvalumab | Experimental | Part A will be a phase 1 dose escalation study of the combination with selumetinib and ZEN-3694.
Part B will be phase 1 study combining the determined dose of selumetinib and ZEN-3694 from Part A with durvalumab.
Part C will be a phase 2 study combining selumetinib, ZEN-3694 with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST. Receives: Combination Product: Selumetinib + ZEN-3694 ± Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety and Tolerability Selumetinib with ZEN-3694
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.
Measured: From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).
Part B: Safety and Tolerability of Durvalumab with Combination of Selumetinib and ZEN-3694
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.
Measured: From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).
Part C: Determine the Clinical Benefit of Selumetinib, ZEN-3694 and Durvalumab
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.
Measured: From first dose through completion of 4 treatment cycles for each participant (up to 112 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2022
- Study start4 Aug 2026
- Primary completion15 Nov 2031 (estimated)
- Study completion15 Nov 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MPNSTStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- Part A will be a phase 1 dose escalation study of the combination with selumetinib and BI. Part B will be phase 1 study combining the determined dose of selumetinib and BI from Part A with durvalumab. Part C will be a phase 2 study combining selumetinib, BI with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Congressionally Directed Medical Research Programs, Children's Hospital of Philadelphia
- Responsible party
- Principal investigator, Girish Dhall, MD, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05253131
- Sponsor's protocol ID
- 300006373
- Other IDs
- W81XWH-17-2-0037 NF160012
- Status last verified
- Aug 2026
- First submitted
- 3 Feb 2022
- Last updated
- 24 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Trial of the MEK Inhibitor Selumetinib and Bromodomain Inhibitor ZEN-3694 With Durvalumab (MEDI4736), a PD-L1 Antibody for Sarcomas Including Malignant Peripheral Nerve Sheath Tumors
- ClinicalTrials.gov ID
- NCT05253131
- Acronym / sponsor ID
- 300006373
- Keywords
- MPNST, Neurofibromatosis 1, NF1, sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Congressionally Directed Medical Research Programs, Children's Hospital of Philadelphia
- Study start
- 4 Aug 2026 (actual)
- Primary completion
- 15 Nov 2031 (estimated)
- Study completion
- 15 Nov 2032 (estimated)
- First posted
- 23 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with ZEN-3694 and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.
Detailed description
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with bromodomain inhibitor (ZEN-3694) and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.
Part A will be a phase 1 dose escalation study of the combination with selumetinib and ZEN-3694.
Part B will be phase 1 study combining the determined dose of selumetinib and ZEN-3694 from Part A with durvalumab.
Part C will be a phase 2 study combining selumetinib, ZEN-3694 with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.
Statistical Plan Phase 1: Conventional dose escalation schema. Cohorts of 3 to 6 participants will be treated per dose level. At the RP2D or last dose level, the cohort may be expanded to up to an additional six participants for further pharmacokinetic and tolerability experience. The MTD/RP2D will be defined as the dose level immediately below the level at which ≥33% of participants in a cohort experience a DLT based on toxicities observed in the first drug therapy cycle.
Phase 2: A Simon's two-stage phase 2 trial of selumetinib, ZEN-3694, and durvalumab to determine the safety and clinical benefit in patients with unresectable or metastatic MPNST Maximum Total Number of Subjects Phase 1: 6-24 participants Phase 2: 9 participants in first stage with additional 8 participants in stage 2.
Target Population Individuals ≥ 18 years of age with relapsed or refractory histologically confirmed sarcoma including MPNST. This may be amended when tolerability is established.
Anticipated Length of Study Maximum enrollment number for entire study is 41participants. It is expected that 15-25 participants will be enrolled per year, and enrollment is expected to be completed in 3 years with follow up after last participant accrual to be approximately 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Part A will be a phase 1 dose escalation study of the combination with selumetinib and BI. Part B will be phase 1 study combining the determined dose of selumetinib and BI from Part A with durvalumab. Part C will be a phase 2 study combining selumetinib, BI with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST.
| Arm | Type | Receives |
|---|---|---|
| Phase 1 and 2 Study of Selumentinib, ZEN-3694 and Durvalumab | Experimental | Combination Product: Selumetinib + ZEN-3694 ± DurvalumabPart A will be a phase 1 dose escalation study of the combination with selumetinib and ZEN-3694. Part B will be phase 1 study combining the determined dose of selumetinib and ZEN-3694 from Part A with durvalumab. Part C will be a phase 2 study combining selumetinib, ZEN-3694 with durvalumab in MPNST patients at the recommended doses from part B. A Simon's two-stage design will be used in the phase 2 trial to determine the clinical benefit in patients with unresectable or metastatic NF associated MPNST. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (96 listed)
- Inclusion Criteria AGE: ≥ 18 years of age Weight: >30 kg Life expectancy of at least 12 weeks
- Part A and B (Phase 1): Patients with histologically confirmed soft tissue or bone sarcoma of the following subtypes:
- MFH/ undifferentiated pleomorphic sarcoma
- Unclassified sarcoma
- Rhabdomyosarcoma
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selumetinib + ZEN-3694 ± DurvalumabSelumetinib and ZEN-3694 administered per protocol, with durvalumab added in later study parts. | Combination product | Phase 1 and 2 Study of Selumentinib, ZEN-3694 and Durvalumab |
Primary outcome
Part A: Safety and Tolerability Selumetinib with ZEN-3694
Time frame: From 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-3694
Time frame: From 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 Durvalumab
Time frame: From 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Selumetinib + ZEN-3694 ± Durvalumab in people with MPNST and NF1, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 96 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Safety and Tolerability Selumetinib with ZEN-3694 (time frame: From first dose through the end of the first treatment cycle for each participant at each dose level (up to 28 days).). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2026.