| Eligibility |
Inclusion Criteria:
1. Male and female subject is 18 years of age or older at the time of signing the
informed consent form (ICF).
2. Subject with histological or cytological confirmation of extensive stage SCLC
according to 2015 WHO classification (Travis, 2015).
3. Subject must be able to provide fresh or archival tumor tissues
4. Subject is found suitable for at least 4 cycles of platinum-based standard
chemotherapy.
5. Subject has at least 1 site of measurable disease per RECIST 1.1.
6. Subject must have the following laboratory values:
• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Hemoglobin (Hgb) = 10 g/dL (= 100 g/L or > 6.2 mmol/L)
- Platelet count (Plt) = 150 x 109/L
- Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase
(AST/SGOT) and alanine aminotransferase/serum glutamate pyruvate transaminase
(ALT/SGPT) = 3.0 x upper limit of normal (ULN) or = 5.0 x ULN if liver metastases
are present
- Serum total bilirubin = 1.5 x ULN
- Serum creatinine = 1.5 mg/dL or creatinine clearance = 60 mL/min (see Appendix G
to see creatinine clearance formula). For the purposes of this protocol, the
glomerular filtration rate (GFR) is considered to be equivalent to the creatinine
clearance.
- Prothrombin time (or international normalized ratio [INR]) and activated partial
thromboplastin time (APTT) = 1.5 ULN
7. Females of childbearing potential (FCBP) must:
• 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.
- Have two negative pregnancy tests as verified by the Investigator prior to
starting CC-90011:
- a negative serum pregnancy test (sensitivity of at least 25 mIU/mL) at
Screening
- a negative serum or urine pregnancy test within 24 hours prior to Cycle 1 Day 1
of study treatment.
- a negative Serum or urine within 24 hours prior to first dose of nivolumab and
then every 4 weeks (± 1 week) regardless of dosing schedule.
- Avoid conceiving for 6 months after last dose of cisplatin or carboplatin or
etoposide, or 5 months after last dose of nivolumab for FCBP, or 45 days after
the last dose of CC-90011, whichever is the latest.
- 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.
8. Males must practice true abstinence from heterosexual intercourse (which must be
reviewed on a monthly basis) or agree to use a condom (a latex condom is recommended)
during sexual contact with a pregnant female or an FCBP and will avoid conceiving from
signing the ICF, while participating in the study, during dose interruptions, and for
6 months after last dose of cisplatin, or carboplatin, or etoposide or at least 105
days following CC-90011 discontinuation, whichever is the latest, even if he has
undergone a successful vasectomy.
9. Males must agree to refrain from donating sperm while on treatment and females must
agree to refrain from donating ova while on treatment and for 6 months after the last
dose of cisplatin or etoposide or 105 days after last dose of CC-90011.
10. Subject is able to swallow pills.
Exclusion Criteria:
1. Subject has received anticancer therapy (either approved or investigational, including
radiation with curative intent) for SCLC prior to study entry.
2. Subject has undergone major surgery = 4 weeks prior to Cycle 1 Day 1 or has not
recovered from surgery.
3. 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 gastrointestinal (GI) disorder that could affect the absorption
of CC- 90011.
4. Subject with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly
those with a history of and/or risk of perforation and GI tract hemorrhages.
5. Subject with any hemorrhage/bleeding event > CTCAE Grade 2 or hemoptysis > 1 teaspoon
within 4 weeks prior to the first dose.
6. Subject with symptomatic and untreated or unstable central nervous system (CNS)
metastases.
7. Subject has impaired cardiac function or clinically significant cardiac diseases,
including any of the following:
- Left ventricular ejection fraction (LVEF) < 45% as determined by multigated
acquisition (MUGA) scan or echocardiogram (ECHO).
- Complete left bundle branch or bifascicular block.
- Congenital long QT syndrome.
- Persistent or clinically meaningful ventricular arrhythmias or atrial fibrillation.
- QTcF = 480 msec on Screening ECG (mean of triplicate recordings).
8. Subject has other clinically significant heart disease such as congestive heart
failure requiring treatment or uncontrolled hypertension (blood pressure = 160/95 mm
Hg).
9. Subject is a pregnant or nursing female.
10. Subject has known human immunodeficiency virus (HIV) infection.
11. Subject has known chronic active hepatitis B or C virus (HBV, HCV) infection.
12. Subject with ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg,
warfarin, low molecular weight heparin, Factor Xa inhibitors, thrombin antagonist).
13. Subject has a history of concurrent second cancers requiring active, ongoing systemic
treatment.
14. Subject has Grade 2 peripheral sensory neuropathy.
15. Subject with poor bone marrow reserve as assessed by Investigator.
16. Subject has any condition including the presence of laboratory abnormalities, which
places the subject at unacceptable risk if he/she were to participate in the study.
17. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.
18. Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20
days for severe/critical illness prior to C1D1.
• Acute symptoms must have resolved and based on investigator assessment in
consultation with the medical monitor, there are no sequelae that would place the
participant at a higher risk of receiving study treatment
19. Previous SARS-CoV-2 vaccine within 7 days of C1D1. For vaccines requiring more than
one dose, the full series (e.g. both doses of a two-dose series) should be completed
prior to C1D1 when feasible and when a delay in C1D1 would not put the study subject
at risk
20. Subject has any condition that confounds the ability to interpret data from the study.
For the subjects treated with nivolumab:
21. Subject has received prior therapies targeting PD-1 or PD-L1
22. Subject has a history of persistent skin rash = NCI CTCAE Grade 2.
23. Subject with an autoimmune disease, or any other condition, requiring systemic
treatment with either corticosteroids within 14 days (> 10 mg daily prednisone
equivalent) or other immunosuppressive medications within 30 days of enrollment.
Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily
prednisone equivalent, are permitted in the absence of active autoimmune disease.
- Subjects with type 1 diabetes mellitus, hypothyroidism only requiring hormone
replacement, disorders (such as vitiligo, psoriasis, or alopecia) not requiring
systemic treatment, or conditions not expected to recur in the absence of an
external trigger are permitted to enroll.
22. Subject has received treatment with botanical preparations (eg, herbal supplements or
traditional Chinese medicines) to treat the disease under study within 2 weeks prior to
randomization. Refer to Section 8.2 for prohibited therapies.
23. Subject has history of allergy or hypersensitivity to study drug components.
24. Subject has received a live/attenuated vaccine within 30 days of first treatment.
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