PRIMARY OBJECTIVE:
I. To determine the recommended phase II dose (RP2D) of protein phosphatase 2A inhibitor
LB-100 (LB-100) when given in combination with standard carboplatin/etoposide/atezolizumab in
treatment naive patients with extensive-stage small cell lung cancer (ED-SCLC).
SECONDARY OBJECTIVES:
I. To assess objective response rate (ORR). II. To assess progression-free survival (PFS).
III. To assess overall survival (OS). IV. To assess duration of overall response (DOR). V. To
assess safety and adverse events (AEs).
EXPLORATORY OBJECTIVES:
I. The pharmacokinetics (PK) of LB-100. II. The biomarkers relevant to LB-100 and the disease
state as well as their correlation to clinical outcomes.
OUTLINE: This is a dose-escalation study of LB-100.
INDUCTION: Patients receive LB-100 intravenously (IV) over 15 minutes on days 1 and 3,
atezolizumab IV over 30-60 minutes on day 1, carboplatin IV over 30-60 minutes on day 1, and
etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 cycles in the
absence of disease progression or unacceptable toxicity.
MAINTENANCE: After completion of induction therapy, patients receive LB-100 IV over 15
minutes on days 1 and 3 and atezolizumab IV over 30 minutes on day 1. Cycles repeat every 21
days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed for up to 30 days, and patients
who discontinue study treatment without disease progression are followed every 6-8 weeks
thereafter.
Inclusion Criteria:
- Histologically or cytologically confirmed extensive-stage disease small cell lung
carcinoma per the Veterans Administration Lung Study Group (VALG) staging system
- Measurable disease as defined by Response Evaluation Criteria in Solid Tumors
(RECIST): Revised RECIST guideline (version 1.1)
- Estimated life expectancy of at least 12 weeks
- For women: Must be surgically sterile (surgical procedure: bilateral tubal ligation),
post-menopausal (at least 12 consecutive months of amenorrhea) or have a negative
pregnancy test. Women of childbearing potential must be compliant with a medically
approved contraceptive regimen (intrauterine device [IUD], birth control pills, or
barrier device) during and for 3 months after the treatment period; must have a
negative serum or urine pregnancy test within 14 days before study drug treatment and
must not be breastfeeding
- For men: agreement to remain abstinent or use medically approved contraceptive
measures, as defined below:
- With female partners of childbearing potential or pregnant female partners, men
must remain abstinent or use a condom during study therapy and for at least 6
months after the last dose of study therapy to avoid exposing the embryo
- A performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale
- Absolute neutrophil (segmented and bands) count (ANC) >= 1.5 x 10/L
- Platelets >= 100 x 10/L
- Hemoglobin >= 9 g/dL
- Bilirubin =< 1.5 times upper limits of normal (ULN) may be enrolled
- Alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) =< 3.0 times ULN (AP, AST, and ALT =< 5 times ULN are
acceptable if the liver has tumor involvement)
- Calculated creatinine clearance (CrCl) >= 45 mL/min based on the Cockcroft and Gault
formula
- All subjects must have the ability to understand and the willingness to sign a written
informed consent
- No prior systemic chemotherapy, immunotherapy, biological, hormonal, or
investigational therapy for SCLC
Exclusion Criteria:
- Currently enrolled in, or discontinued within the last 30 days from, a clinical trial
involving an investigational product or non-approved use of a drug or device, or
concurrently enrolled in any other type of medical research judged not to be
scientifically or medically compatible with this study
- Diagnosis of non-small cell lung cancer (NSCLC) or mixed NSCLC and small cell lung
cancer (SCLC)
- No prior malignancy other than SCLC, carcinoma in situ of the cervix, or nonmelanoma
skin cancer, unless that prior malignancy was diagnosed and definitively treated 5 or
more years prior to study entry with no subsequent evidence of recurrence. Patients
with a history of low grade (Gleason score =< 6 = Gleason group 1) localized prostate
cancer will be eligible even if diagnosed less than 5 years prior to study entry
- Serious concomitant systemic disorder that, in the opinion of the investigator, would
compromise the patient's ability to adhere to the protocol
- Active or ongoing infection during screening requiring the use of systemic antibiotics
- Serious cardiac condition, such as myocardial infarction within 6 months, angina, or
heart disease as defined by the New York Heart Association class III or IV
- Clinical evidence of central nervous system (CNS) metastases or leptomeningeal
carcinomatosis, except for individuals who have previously-treated CNS metastases, are
asymptomatic, and have had no requirement for steroid medication for 1 week prior to
the first dose of study drug and have completed radiation 2 weeks prior to the first
dose of study drug
- Known or suspected allergy to any agent given in association with this trial
- Pregnant or lactating women
- History of autoimmune disease, including minor/mild autoimmune disease not requiring
immunosuppressants (such as eczema on less than 10% of the body surface area and long
term diabetes mellitus type 1 on stable insulin)
- Active, known hepatitis B or hepatitis C
- Human immunodeficiency virus (HIV) positive
- Treatment with systemic corticosteroid or other immunosuppressive medication. The use
of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension,
and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed
- Administration of a live, attenuated vaccine within 28 days prior to study
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently). Patients with indwelling
catheters are allowed
- Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium >
12 mg/dL or corrected serum calcium > ULN). Patients who are receiving denosumab prior
to study entry must be willing and eligible to discontinue its use and replace it with
a bisphosphonate while in the study
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest computed tomography (CT) scan. History of radiation
pneumonitis in the radiation field (fibrosis) is permitted
- Prior allogeneic bone marrow transplantation or solid organ transplant
- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study
