DS-3201b and Irinotecan for Patients With Recurrent Small Cell Lung Cancer

Inclusion Criteria

• •Signed informed consent form (ICF)
• •Ability to comply with the study protocol as per the investigator's judgment
• •Age ≥ 18 years at the time of signing the ICF
• •Life expectancy ≥ 12 weeks
• •Karnofsky performance status ≥ 70% or ECOG 0, -1 or 2
• •Pathologically confirmed diagnosis of small cell lung cancer. Patients with a diagnosis of combined small cell lung cancer with other histologies may be considered for inclusion if the predominant histology is SCLC and only after discussion with the study PI. Patients with transformed SCLC from NSCLC are allowed on study after discussing with the MSKCC or JHU Study PI
• •Radiographically documented progression of disease after prior treatment with a platinum doublet regimen. Patients who received a platinum doublet regimen in combination with immunotherapy are still eligible for the study.
• •Measurable disease according to RECIST v1.1
• •Adequate tissue sample available for both IHC testing of IHC testing of SLFN11 and H3K27me3 and molecular profiling (archived tissue block or 20 unstained slides). Tissue sample can be either from an initial pre-platinum-based chemotherapy sample OR from a repeat biopsy sample after progression on platinum-based chemotherapy.
• •Concurrent consent to the appropriate biospecimen research protocols at MSKCC (#06-107 Storage and Research Use of Human Biospecimens) and at JHU.
• •Adequate hematologic and end-organ function, as defined by the following laboratory test results obtained within 14 days prior to initiation of study treatment:
• •°Adequate bone marrow function as defined by:
• •* Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (1500/µL) without granulocyte colony-stimulating factor support within 2 weeks prior to starting study therapy
• •* Hemoglobin ≥ 9 g/dL (transfusions to meet this criterion are allowed)
• •* Platelets ≥ 150 x 10\^9/L without transfusion
• •Adequate renal function as defined by:
• •°Creatinine clearance ≥ 50 mL/min as calculated using the modified Cockcroft-Gault equation or Modification of Diet in Renal Disease (MDRD) formula OR serum creatinine ≤1.5 x ULN
• •Adequate hepatic function as defined by:
• •* AST, ALT, and alkaline phosphatase (ALP) ≤ 3 x ULN with the following exceptions
• •* Patients with documented liver metastases: AST, ALT and ALP ≤ 5 x ULN
• •* Total bilirubin ≤ 2.0 mg/dL
• •* For patients not receiving therapeutic anticoagulation:
• •* stable anticoagulant regimen
• •* INR ≤ 1.5 x ULN
• •* aPTT ≤ 1.5 x ULN
• •Patients with baseline clinical symptoms or laboratory abnormalities that do not meet the definition of dose-limiting toxicity (DLT).
• •Nonsterilized female patients of reproductive age group and male patients should use highly effective methods of contraception through defined periods during and after study treatment as specified below:
• •* Female patients must meet 1 of the following:
• •* Postmenopausal for at least 1 year before the screening visit, or
• •* Surgically sterile, or
• •* If she is of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or
• •* Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
• •* Female patients must agree to not donate eggs (ova) during the course of this study or 4 months after receiving their last dose of study drug(s).
• •* A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
• •* Examples of highly effective contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, and established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• •* Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to
• •1. of the following:
• •* Practice highly effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or
• •* Practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\] withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
• •* Male patients must agree to not donate sperm during the course of this study or 6 months after receiving their last dose of study drug(s).
• •* Patient is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• •* Myocardial infarction within 6 months prior to Screening
• •* Angioplasty or stent graft implantation within 6 months prior to Screening
• •* Uncontrolled angina pectoris within 6 months prior to Screening
• •* New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
• •* Coronary/peripheral artery bypass graft within 6 months prior to Screening
• •* Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg) Complete left or right bundle branch block
• •Patients who are currently taking medications that are known to prolong the QT interval and are clearly associated with a known risk of Torsades de Pointes (TdP) even when taken as recommended. Please see Section 11.6 for a full list of excluded medications. Patients who are able to discontinue any prohibited medication prior to the start of study drug at Day -7 will still be considered eligible for the study.
• •Have a known hypersensitivity to any of the components of or known hypersensitivity to either the study drug itself or any of the inactive ingredients in the study drug product.
• •Known liver cirrhosis.
• •Uncontrolled active infection requiring IV antibiotic, antiviral, or anti-fungal medications within 14 days prior to initiation of study treatment.
• •°Infections controlled on concurrent anti-microbial agents and anti-microbial prophylaxis per institutional guidelines are acceptable.
• •Congenital or acquired immunodeficiency, including patients with known history or infection with human immunodeficiency virus (HIV).
• •°NOTE: HIV-positive patients who are taking anti-retroviral therapy are still ineligible due to potential PK interactions with DS-3201b.
• •Active tuberculosis
• •Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test Hepatitis B testing (HBV surface antigen and core antibody) is required only if not done previously
• •°Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test, are eligible for the study. Hepatitis B testing is required only if not done previously
• •Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test. Hepatitis C testing (HCV antibody) is required only if not done previously
• •°The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
• •Female patients who have a positive serum pregnancy test during screening or a positive urine pregnancy test on Day 1 before first dose of study drug.
• •Female patients who are lactating and/or plan to breastfeed during the study treatment.