A Phase 1b, open-label, dose-finding study of CC-90010 in combination with temozolomide with or without radiation therapy in subjects with newly diagnosed glioblastoma

Only part A
- For Adjuvant Therapy in Part A dose scalation: Subject must have recently
completed standard or a hypofractionated course of radiotherapy with TMZ
chemotherapy, and then have an MRI documenting stable disease prior to the
first dose of CC -90010.
- For Adjuvant Therapy in Part A dose escalation:
a. All AEs resulting from prior RT+TMZ chemotherapy must have resolved to
NCI CTCAE (v5.0) Grade **1 (except for laboratory parameters outlined below
b. Subject must have not experienced significant toxicity to prior RT+TMZ
(i.e.,ie, Grade 4 hematological toxicity)
c. Subject must have received at least 80% of the planned standard doses of RT
and/or TMZ administered throughout the 42- day concomitant period (up to 49
days).
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 in
Part A.

Only part B
- For Part B randomized expansion, only subjects with primary, IDH-wild type
newly diagnosed WHO Grade IV Glioblastoma will be enrolled. Prior to
randomization, IDH mutation testing using sequencing must have been performed
in subjects <= 55 years of age or in subjects with a history of a low grade
glioma. In subjects > 55 years of age, a negative immunohistochemistry for the
IDH R132 mutation is sufficient evidence of an IDH-wild type Glioblastoma.
- For Part B randomized expansion, MGMT promoter methylation status must be
available prior to randomization. This is based on evaluation of tumor tissue
from surgical resection (done locally).
- Part B expansion, a post-operative baseline contrast-enhanced MRI scan must
be obtained to be used for stratification of randomization. It is strongly that
this scan be obtained <72 hours post-surgery (preferably within 24-48 hours
post-surgery).
- Karnofsky performance status of >=70 in Part B.
- Subject must have stable or decreasing dose of steroids at least 1 week prior
to start of treatment (Day 1). Dose at randomization must be <= 20 mg prednisone
or <= 3 mg dexamethasone daily (or equivalent).
- Archival tumor specimens are mandatory in Part B Randomized expansion.

Inclusion Criteria for both part A and part B
- Males and females of >= 18 years of age
- Subject must understand and voluntarily sign an ICF prior to any study-related
assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule and other
protocol requirements.
- Subject has newly diagnosed, histologically confirmed WHO Grade IV
Glioblastoma and must have undergone complete or partial tumor resection.
- Subject must have recovered from the effects of surgery, including
post-operative infections or complications.
- Prior tumor resection up to 8 weeks (preferably within 6 weeks) prior to the
first dose of CC-90010.
- Subject with archival tumor tissue suitable for molecular genetic testing
must give permission to access and test the tissue.
- Subject must have the normal laboratory values described on the protocol at
screening.
- Females of childbearing potential (FCBP) :
o Either commit to true abstinence from heterosexual contact (which must be
reviewed on a monthly basis and source documented) or agree to use, one highly
effective contraceptive method plus one barrier method. These measures should
be used from signing the ICF, throughout the study (including dose
interruptions), and for at least 6 months and 16 days following the last dose
of CC 90010 and at least 180 days after the last dose of TMZ.
o Have two negative pregnancy tests as verified by the Investigator prior to
starting CC-90010 and TMZ+RT or TMZ+RT:
• a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
Screening
• a negative serum or urine pregnancy test (Investigator*s discretion) within
72 hours prior to Cycle 1 Day 1 of study treatment
o Avoid conceiving for at least 6 months and 16 days after the last dose of
CC-90010 and for at least 180 days after the last dose of TMZ. The longest
contraception period that is required must be followed (eg6 months and 16 days
after the last dose of study drug, instead of 180 days).
o Agree to ongoing pregnancy testing during the course of the study, and after
the end of study treatment. This applies even if the subject practices true
abstinence from heterosexual contact.
o Females must agree to refrain from donating ova while on study treatment and
for 6 months and 16 days after the last dose of CC-90010 or 180 days after the
last dose of TMZ, whichever is longer.

Applicable for Part A and Part B:
1. Prior chemotherapy or other anti-tumor treatment for GBM
2. Any known metastatic extracranial or leptomeningeal disease.
3. Secondary GBM
4. Subjects with indeterminate MGMT promoter methylation status.
5. Biopsy only of GBM at surgery, defined as < 20% resection of enhancing tumor.
6. Subject has persistent diarrhea due to a malabsorptive syndrome (such as
celiac sprue or
inflammatory bowel disease) NCI CTCAE Grade >= 2, despite medical management, or
any other significant GI disorder that could affect the absorption of CC-90010.
7. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal),
particularly those
with a history of and/or risk of perforation and GI tract hemorrhages.
8. Evidence of recent, symptomatic CNS hemorrhage on baseline MRI or CT scan
and/or
CNS hemorrhage of Grade > 1 on baseline MRI scan
9. Subject who requires increasing doses of corticosteroids to treat
symptomatic cerebral
edema within 14 days prior to the first dose of CC-90010.
10. Known symptomatic acute or chronic pancreatitis.
11. Impaired cardiac function or clinically significant cardiac diseases as
defined in the protocol
12. Pregnant or nursing females.
13. Known HIV infection.
14. Known chronic active hepatitis B or C virus (HBV, HCV) infection
15. Subject with a requirement for ongoing treatment with therapeutic dosing of
anticoagulants or for ongoing prophylactic anticoagulation.
16. History of concurrent second cancers requiring active and ongoing systemic
treatment
17. Evidence of history of bleeding diathesis.
18. Subject with known prior episodes of non-arteritic anterior ischemic optic
neuropathy
(NAION) should be excluded from the study.
19. Subject has any significant medical condition in the study or would place
the subject at unacceptable risk if he/she were to participate in the study.
20. Subject has any condition that confounds the ability to interpret data from
the study.
21. Subject with poor bone marrow reserve as assessed by Investigator such as
in conditions
requiring regular hematopoietic support
22. Previous SARS-CoV-2 infection
23. Previous SARS-CoV-2 vaccine within 14 days of C1D1.

Additional exclusion criteria for Part B:
- The following therapies are not allowed:
a. Prior use of Gliadel wafers or any other intratumoral or intracavitary
treatment.
b. Planned additional treatment with Tumor-treating Fields.
- Any known metastatic extracranial or leptomeningeal disease.
- Secondary GBM (ie, progression from prior low-grade or anaplastic glioma)
- Subjects with indeterminate MGMT promoter methylation status in Part B.
- Biopsy only of GBM at surgery, defined as < 20% resection of enhancing tumor.
- Evidence of recent, symptomatic CNS hemorrhage on baseline MRI or CT scan
and/or CNS hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently
documented to have resolved.