A Drug Interaction Study to Assess the Effect of LY2603618 on the Metabolic Pathway of Desipramine

The purpose of this study is to assess the effect LY2603618 on a protein \[enzyme cytochrome P (CYP) 2D6\] which is involved in the metabolic pathway of Desipramine in participants with cancer. This is a drug interaction study so the treatment of the disease will not be the main purpose of the study.

The study involves two single doses of 50 milligrams (mg), 1 tablet by mouth, on Day 1 of Period 1 and 2. In Period 1 Desipramine will be administered alone. In Period 2 Desipramine will be administered in combination with LY2603618. LY2603618 will be administered as a 275mg intravenous (IV) infusion over 1 hour (hr).

Desipramine will be administered at the end of the LY2603618 infusion. Information about any side effects that may occur will also be collected.


Eligibility Criteria:
Inclusion Criteria:

* Have a histological or cytological diagnosis of cancer (solid tumor), with clinical or radiologic evidence of locally advanced and/or metastatic disease, for which no life-prolonging therapy exists (that is, refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists). Note: Participants who have had progressive disease after receiving pemetrexed for metastatic disease are excluded from receiving the combination with pemetrexed during the safety extension study. Participants who have had progressive disease after receiving gemcitabine for metastatic disease are excluded from receiving the combination with gemcitabine during the safety extension study.
* Have a body surface area (BSA) greater than or equal to 1.37 square meters (m²)
* Have given written informed consent prior to any study-specific procedures
* Have adequate hematologic, hepatic and renal function
* Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
* Have discontinued all previous treatments for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy or other investigational therapy for at least 30 days prior to study entry and recovered from the acute effects of therapy (at least 42 days for mitomycin-C or nitrosoureas, or 60 days for biologics)
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
* Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for at least 3 months following the last dose of study drug
* Females with childbearing potential: Have had a negative serum pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding
* Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete 1 full cycle of treatment beyond the drug interaction portion of the study (approximately 8 weeks)
* Are able to swallow tablets
* Prior radiation therapy for treatment of cancer is allowed to \<25% of the bone marrow and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry.

Exclusion Criteria:

* Have received treatment within 28 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication
* Poor metabolizer (PM) status for CYP2D6 (genotyped)
* Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other checkpoint kinase one (Chk1) inhibitor
* Have known allergy to gemcitabine, pemetrexed, desipramine or LY2603618 or any ingredient of gemcitabine, pemetrexed, desipramine or LY2603618 (like Captisol®)
* Have serious preexisting medical conditions (left to the discretion of the investigator) other than advanced cancer
* Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 90 days.
* Have current hematologic malignancies or either acute or chronic leukemia
* Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required)
* Have QTc interval of \>500 milliseconds (msec) on screening electrocardiogram (ECG)
* Have ECG abnormalities on the screening ECG such as significant conduction abnormalities, ischemic changes (such as prior Q-wave myocardial infarction and/or marked ischemic ST- and T-wave), arrhythmias (such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation), or other ECG abnormalities that would put the participant at unnecessary risk in the opinion of the investigator
* Drugs with narrow therapeutic windows and that are also known substrates of CYP2D6 or drugs that are classified as sensitive substrates of CYP2D6 are excluded
* Drugs or herbal supplements that are known inhibitors of CYP2D6 are excluded during the study, and during the 30-day period (or a minimum of 5 half-lives, whichever is less) prior to study start
* Participants who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or participants unwilling to stop alcohol consumption for 24 hours before the study through the end of the study