A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer

Inclusion Criteria

The patients must satisfy all of the following inclusion/exclusion criteria in order to be eligible for the study:

• Must have signed and dated written informed consent form in accordance with regulatory and institutional guidelines.
• Males and females aged >18 years at time of consent.
• Histological or cytological confirmed extensive-stage SCLC
• Patients who progressed after at least 1 platinum-based chemotherapy regimen. Patients with platinum resistance (defined as recurrence or progression of disease within 90 days of completion of the platinum-based regimen) are eligible. For phase II, patients also must have been treated with at least one prior line of PD-1/PD-L1 therapy.
• Measurable disease according to RECIST v1.1 (Section 8) obtained by imaging within 28 days prior to study registration.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before registration and minimum life expectancy of at least 12 weeks.
• Treatment to be initiated at least 2 weeks since last dose of prior systemic anticancer therapy (chemotherapy, radiation, and/or surgery.
• Recovery to grade 1 of any clinically significant toxicity (excluding alopecia, grade 2 fatigue, vitiligo, endocrinopathies on stable replacement therapy) prior to initiation of study drugs.
• Female patients of childbearing potential have a negative pregnancy test at baseline. Females of childbearing potential are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti estrogens, or ovarian suppression.
• Women of childbearing potential (i.e., menstruating women) must have a negative urine pregnancy test (positive urine tests are to be confirmed by serum test) documented within 14 days of study registration and within the 24-hour period prior to the first dose of study drug.
• Sexually active women of childbearing potential enrolled in the study must agree to use 2 forms of accepted methods of contraception during the course of the study and for 23 weeks after their last dose of study drug. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) on stable doses of hormonal contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner.
• For male patients who are sexually active and who are partners of premenopausal women: agreement to use 2 forms of contraception as in criterion 9b above during the treatment period and for 31 weeks after the last dose of study drug.
• Adequate laboratory values.
• Absolute neutrophil count ≥1,000/µL
• Platelet count ≥100,000/µL
• Hemoglobin ≥9.0 g/dL
• Total bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN for subjects with Gilbert's disease
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN if evidence of hepatic involvement by malignant disease)
• Creatinine ≤ 1.5 x ULN or estimated glomerular filtration rate (eGFR) ≥40 mL/min/1.73m2
• Lipase and Amylase ≤1.5 x ULN. Subjects with Lipase >1.5 x ULN may enroll if there are neither clinical nor radiographic signs of a pancreatitis.

Exclusion Criteria

Patients with any of the following will be excluded from participation in the study.

• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids. Prior history of radiation pneumonitis is allowed if pneumonitis was restricted to the field of radiation.
• History of ileus or other significant gastrointestinal disorder known to increase the risk of ileus or chronic bowel h