Clinical research Study to find out if the study drug INCB059872 is safe and effective in people who have Ewing sarcoma.

Phase 1

• Conditions: Relapsed or Refractory Ewing Sarcoma; MedDRA version: 20.0Level: PTClassification code 10015560Term: Ewing's sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-000062-11-GB
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-26
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

1. The participant (or legally acceptable representative if applicable) provides written informed consent for the study.
2. The participant must be 12 years of age or older, at the time of signing the informed consent.
3. Have histologically or cytologically confirmed diagnosis of Ewing sarcoma and have progressed on or after standard therapies.
4. The participant must not be a candidate for potentially curative therapy or standard-of-care approved therapy.
5. Have measurable disease by CT or MRI based on RECIST 1.1 as determined by site radiology.
6. ECOG performance status 0 to 2.
7. Baseline archival tumor specimen available or if an archived sample is not available, a predose core tumor biopsy will be required in order to enter the study. Archived specimens must be an FFPE tumor block with sufficient tumor for 15 consecutive sections or 15 unstained slides from biopsy or resection of primary tumor that is preferably = 1 year old and obtained after completion of last treatment. Fine needle aspiration and/or brushing biopsy are not acceptable. If a fresh biopsy is not feasible, discuss with sponsor medical monitor.
8. Willingness to avoid pregnancy or fathering children based on the criteria below.
a. Male participants must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study drug(s) and refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.
b. Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR = 12 months of amenorrhea).
c. Woman of childbearing potential who has a negative serum pregnancy test at screening and negative urine pregnancy test before the first dose on Day 1 and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the participant and their understanding confirmed.
Are the trial subjects under 18? yes
Number of subjects for this age range: 13
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Receipt of anticancer medications, anticancer therapies, or investigational drugs within the following interval before the first administration of study drug (requirement may be waived with medical monitor approval):
a. < 6 weeks for mitomycin or nitrosoureas.
b. < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication).
c. < 5 half-lives for all other anticancer medications (unless approved by sponsor).
d. < 4 weeks for immunotherapy or antibody therapy.
2. Participants must have recovered (= Grade 2 or at pretreatment baseline) from AEs from previously administered therapies except for stable chronic toxicities (= Grade 2) not expected to resolve.
3. Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
4. Untreated brain or CNS metastases or brain/CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases). Participants with previously treated and clinically stable brain/CNS metastases who are receiving concomitant corticosteroids must be on a stable or decreasing dose for at least 2 weeks (equivalent to = 10 mg/day) or off of all corticosteroids for at least 2 weeks before the first dose of study treatment.
5. Prior radiotherapy within 2 weeks of study treatment. Participants must have recovered from all radiation-related toxicities, including radiation pneumonitis, and not require corticosteroids. Evidence of fibrosis within a radiation field from prior radiotherapy is permitted with medical monitor approval. A 1-week washout period is permitted for palliative radiation to non-CNS disease with medical monitor approval.
6. Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
7. Unless approved by the medical monitor, receipt of autologous hematopoietic stem cell transplant within 3 months before receiving the first dose of study drug(s), receipt of allogeneic stem cell transplant within 6 months before receiving the first dose of study drug(s), or active graft-versus-host disease after transplant, or receipt of immunosuppressive therapy following allogeneic transplant within 2 weeks of Cycle 1 Day 1 (prednisone = 10 mg/day is allowed).
8. Participants with laboratory values at screening, without transfusions and hematopoietic growth factor support, defined in Table 6 (transfusions are permitted to achieve required hemoglobin level that remains above = 9 g/L for at least 2 weeks).
10. History or evidence of bleeding disorder or active clinically significant bleeding requiring medical intervention.
11. Has a significant concurrent, uncontrolled medical condition, including but not limited to the following:
a. GI
- Inability of the participant to swallow and retain oral medication.
b. Cardiovascular
- Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, and unstable arrhythmia requiring therapy unless approved by medical monitor/sponsor.
- History or presence of an abnormal ECG, which, in the

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of INCB059872 in participants with relapsed/refractory Ewing sarcoma.;Secondary Objective: - To evaluate the antitumor activity of INCB059872 in participants with relapsed/refractory Ewing sarcoma, endpoint: ORR.<br>- To evaluate the PK of INCB059872.;Primary end point(s): Safety and tolerability as assessed by monitoring the frequency, severity, and duration of AEs through physical examinations, by evaluating changes in vital signs and ECGs, and through clinical and laboratory assessments.;Timepoint(s) of evaluation of this end point: Throughout the whole duration of the study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - ORR, defined as the percentage of participants who have a CR or PR as determined by investigator assessment of response in accordance with RECIST v1.1<br>- PK parameters including Cmax, tmax, Cmin, AUC, t½, Cl/F.;Timepoint(s) of evaluation of this end point: Throughout the whole duration of the study.