LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer

• Status: Recruiting
• Trial end date: 2023-08-08
• Target enrollment: 0
• Participant gender: All

Summary

This phase Ib trial studies the side effects and best dose of LB-100 when given together with carboplatin, etoposide, and atezolizumab for the treatment of untreated extensive-stage small cell lung cancer. Drugs such as carboplatin and etoposide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. LB-100 has been shown to make anticancer drugs (chemotherapy) work better at killing cancer. LB-100 blocks a protein on the surface of cells called PP2A. Blocking this protein makes the tumor cells that express PP2A divide. This allows standard chemotherapy drugs such as carboplatin, etoposide, and atezolizumab work better at killing the tumor cells since these drugs work best at destroying cells that are dividing. Giving LB-100 in combination with standard chemotherapy drugs may work better to treat extensive-stage small cell lung cancer compared to standard chemotherapy drugs alone.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Antibodies, Monoclonal; Atezolizumab; Carboplatin; Etoposide; Etoposide phosphate; LB100; Podophyllotoxin

Criteria

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