Study of Romiplostim for Chemotherapy-induced Thrombocytopenia in Adult Subjects With Non-small Cell Lung Cancer (NSCLC), Ovarian Cancer, or Breast Cancer

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study-specificactivities/procedures or subject's legally acceptable representative has providedinformed consent prior to any study-specific activities/procedures being initiatedwhen the subject has any kind of condition that, in the opinion of the investigator,may compromise the ability of the subject to give written informed consent.

• Males or females greater than or equal to 18 years of age at signing of the informedconsent.

• Documented active stage I, II, III or IV locally advanced or metastatic of thefollowing tumor types: NSCLC, breast cancer, or ovarian cancer (includes fallopiantube epithelial carcinomas and peritoneal epithelial carcinoma of unknown primary),or any stage recurrent disease. Patients with documented locally advanced (stageIII) NSCLC should not be amenable to definitive treatment with chemoradiation and/orsurgery.

• Subjects must be receiving cancer treatment with 21- or 28-day cycles, using one ofthe following carboplatinum-based combination chemotherapy regimens:carboplatin/gemcitabine based, carboplatin/pemetrexed based, carboplatin/liposomaldoxorubicin based or carboplatin/taxane based (which includes either paclitaxel,nab-paclitaxel, or docetaxel) or single agent chemotherapy regimen with any of theabove mentioned drugs. Use of combination regimens with one of the abovecarboplatinum-based regimens is permitted with (1) anti-angiogenic agents (such asbevacizumab); (2) targeted therapy (such as anti-epidermal growth factor agents oranti- human epidermal growth factor receptor 2) or (3) immune checkpoint inhibitors.Cycle duration is based on intervals between day 1 of chemotherapy cycles (overlapping with carboplatin intervals) every 21 or 28 day cycles for single agentregimens. OR, Subjects must have CIT from a non-protocol chemotherapy regimen,planning to start treatment with one of the above protocol chemotherapy regimenswhich has been delayed ≥ 1 week due to CIT.

• Subjects must have a local platelet count ≤ 85 x 109/L on day 1 of the study.

• Subjects must be at least 21 or 28 days removed from the start of the chemotherapycycle immediately prior to study day 1 if receiving a 21-day or 28-day cyclechemotherapy regimen, respectively.

• Subjects must have at least 3 remaining planned cycles of chemotherapy at studyenrollment.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Exclusion Criteria:

• Acute lymphoblastic leukemia.

• Acute myeloid leukemia.

• Any myeloid malignancy.

• Myelodysplastic syndrome. Baseline bone marrow biopsy is not required to rule outMDS. However, if a bone marrow biopsy and cytogenetics were performed as part ofdiagnostic or staging work-up, these results will be collected to confirm.

• Myeloproliferative disease.

• Multiple myeloma.

• Within 4 months prior to enrollment, any history of active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia,uncontrolled arrhythmias, clinically significant electrocardiogram (ECG)abnormalities, screening ECG with corrected QT (QTc) interval of greater than 470msec, pericardial disease, or myocardial infarction.

• Major surgery less than or equal to 28 days or minor surgery less than or equal to 3days prior to enrollment.

• New or uncontrolled venous thromboembolism or thrombotic events within 3 monthsprior to screening. To be eligible, subjects must have received at least 14 days ofanticoagulation for a new thrombotic event and considered to be stable and suitablefor continued therapeutic anticoagulation during trial participation.

• History of arterial thrombotic events (eg, myocardial ischemia, transient ischemicattack, or stroke) within 6 months prior to screening.

• Evidence of active infection within 2 weeks prior to the first dose of studytreatment.

• Known human immunodeficiency virus infection with any detectable viral load atscreening. Subjects without a documented diagnosis in their medical history willrequire a local laboratory assessment at screening. If local laboratory results arenot available use central laboratory results.

• Known active of chronic hepatitis C or hepatitis B infection. Subjects without adocumented diagnosis in their medical history will require a local laboratoryassessment at screening. If local laboratory results are not available use centrallaboratory results. Hepatitis B and C infection is based on the following results:

• Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis Bor recent acute hepatitis B).

• Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA bypolymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNAsuggests occult hepatitis B.

• Positive hepatitis C virus antibody: hepatitis C virus RNA by PCR is necessary.Detectable hepatitis C virus RNA suggests chronic hepatitis C.

• In addition to the conditions listed in exclusion criteria 201 through 206,secondary malignancy within the past 5 years except:

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence ofdisease.

• Adequately treated cervical carcinoma in situ without evidence of disease.

• Adequately treated breast ductal carcinoma in situ without evidence of disease.

• Prostatic intraepithelial neoplasia without evidence of prostate cancer.

• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.

• Malignancy treated with curative intent and with no known active disease present forgreater than or equal to 3 years before enrollment and felt to be at low risk forrecurrence by the treating physician (excluding malignancies listed in exclusioncriteria 201 - 206).

• Thrombocytopenia due to another etiology other than CIT (eg, chronic liver disease,prior history of immune thrombocytopenia purpura).

• Any combined modality regimen containing radiation therapy or surgery occurringconcomitantly with neo-adjuvant chemotherapy or where radiation therapy is plannedduring the cycle preceding 3 planned on-study cycles of chemotherapy.

Prior/Concomitant Therapy:

• Previous use of romiplostim, pegylated recombinant human megakaryocyte growth anddevelopment factor, eltrombopag, recombinant human TPO, any other TPO receptoragonist, or any investigational platelet producing agent.

Prior/Concurrent Clinical Study Experience - Currently receiving (or plan to receive) treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

Diagnostic Assessments

• Anemia (hemoglobin < 80 g/L [8 g/dL]) on the day of initiation of investigationalproduct as assessed by local labs. Use of red cell transfusions and erythropoieticstimulating agents is permitted throughout the study as per institutionalguidelines.

• Neutropenia (absolute neutrophil count less than 1 x 10 9/L) on the day ofinitiation of investigational product as assessed by local labs. Use ofgranulocyte-colony stimulating factor is permitted throughout the study as perinstitutional guidelines.

• Abnormal renal function with creatinine clearance less than 30 mL/min using theCockcroft-Gault estimated creatinine clearance as assessed by local laboratory. Iflocal laboratory results are not available use central laboratory results.

during screening.

• Abnormal liver function (total bilirubin greater than 3X ULN; alanineaminotransferase [ALT] or aspartate aminotransferase [AST] greater than 3X ULN forsubjects without liver metastases or greater than or equal to 5X ULN for subjectswith liver metastases) as assessed by local laboratory during screening. If locallaboratory results are not available use central laboratory results.

Other Exclusions

• Females who are pregnant or breastfeeding or planning to become pregnant orbreastfeed during treatment and for an additional 7 months after treatment (andchemotherapy) discontinuation (females of childbearing potential should only beincluded after a confirmed menstrual period and a negative highly sensitive urine orserum pregnancy test.)

• Females of childbearing potential unwilling to use a highly effective method ofcontraception during treatment and for an additional 7 months after treatment (andchemotherapy) discontinuation. Refer to Appendix 5 for additional contraceptiveinformation.

• Males unwilling to use contraception* (male condom or sexual abstinence) or theirfemale partner(s) of childbearing potential who are unwilling to use a highlyeffective method of contraception during treatment (and chemotherapy) and for anadditional 7 months after treatment (and chemotherapy) discontinuation. *If themale's sole partner is of non-childbearing potential, he is not required to useadditional forms of contraception during the study.

• Subject has known sensitivity to any of the products to be administered duringdosing.

• Subject likely to not be available to complete all protocol-required study visits orprocedures, and/or to comply with all required study procedures (eg, COAs) to thebest of the subject and investigator's knowledge.

• History or evidence of any other clinically significant disorder, condition ordisease (with the exception of those outlined above) that, in the opinion of theinvestigator or Amgen physician, if consulted, would pose a risk to subject safetyor interfere with the study evaluation, procedures or completion.

• Male subjects with a pregnant partner who are unwilling to practice abstinence oruse a condom during treatment (and chemotherapy) and for an additional 7 monthsafter treatment (and chemotherapy) discontinuation.

• Male subjects unwilling to abstain from donating sperm during treatment (andchemotherapy) and for an additional 7 months after treatment (and chemotherapy)discontinuation.