A Phase 1 Study in Participants With Advanced Cancer

• Determination of a Recommended Phase 2 Dosing Regimen: Maximum Tolerated Dose (Parts A and B) [ Time Frame: Time of first dose until last dose (estimated as up to 156 weeks) ] [ Designated as safety issue: Yes ]
• Determination of Clinically Significant Safety Effects (Parts A and B) [ Time Frame: Time of first dose until last dose (estimated as up to 156 weeks) ] [ Designated as safety issue: No ]
• Percentage of Participants With a Complete or Partial Response (Overall Response Rate) (Part C) [ Time Frame: Baseline until disease progression or death from any cause (estimated as up to 24 weeks) ] [ Designated as safety issue: No ]

• Determination of a recommended Phase 2 dosing regimen [ Time Frame: Time of first dose until last dose ] [ Designated as safety issue: Yes ]
• Determination of clinically significant safety effects [ Time Frame: Time of first dose until last dose ] [ Designated as safety issue: Yes ]

• Percentage of Participants with Complete Response, Partial Response, or Stable Disease (Disease Control Rate) (Parts A, B, and C) [ Time Frame: Baseline until disease progression or death from any cause (estimated as up to 24 weeks) ] [ Designated as safety issue: No ]
• Progression Free Survival (Parts B and C) [ Time Frame: Baseline to measured progressive disease (estimated up to 24 weeks) ] [ Designated as safety issue: No ]
• Duration of Response (Parts B and C) [ Time Frame: First observation of complete response (CR), partial response (PR), or stable disease (SD) to first observation of progressive disease or death (estimated up to 24 weeks) ] [ Designated as safety issue: No ]
• Preliminary Pharmacokinetics of LY2606368 (Cmax) (Parts A, B, and C) [ Time Frame: During Cycles 1 and 2 ] [ Designated as safety issue: No ]
• Preliminary Pharmacokinetics of LY2606368 (AUC) (Parts A, B, and C) [ Time Frame: During Cycles 1 and 2 ] [ Designated as safety issue: No ]

• Part A: document any antitumor activity [ Time Frame: During every cycle and initial follow-up visit ] [ Designated as safety issue: No ]
• Part B: Clinical benefit rate by number of complete response (CR), partial response (PR) and stable disease (SD) [ Time Frame: 6 weeks after initiation of treatment and every 6 weeks following until patient discontinues ] [ Designated as safety issue: No ]
• Part B: Progression Free Survival [ Time Frame: baseline to measured progressive disease ] [ Designated as safety issue: No ]
• Part B: Duration of response [ Time Frame: First observation of complete response (CR) or partial response (PR) to first observation of progressive disease or death ] [ Designated as safety issue: No ]
• Part A and B: Preliminary pharmacokinetics of LY2606368 (Cmax) [ Time Frame: During Cycles 1 and 2 ] [ Designated as safety issue: No ]
• Part A and B: Preliminary pharmacokinetics of LY2606368 (AUC) [ Time Frame: During cycles 1 and 2 ] [ Designated as safety issue: No ]

The primary purpose of Parts A and B of this study is to evaluate the safety and toxicity of LY2606368 (an inhibitor of checkpoint kinase 1[chk 1]) in participants with advanced or metastatic cancer (Part A), or squamous cell cancer of the head and neck or squamous cell cancer of any tumor type (Part B). Part C of the study will evaluate LY2606368 in three different groups of participants; those with squamous cell cancer of the head and neck that has recurred or spread to other parts of the body, those with squamous non-small cell lung cancer that has recurred or spread, and those with squamous cell cancer of the anus that is not curable by existing therapy.

Part C added per protocol amendment (February, 2013).

• Advanced Cancer
• Squamous Cell Carcinoma
• Carcinoma, Squamous Cell of Head and Neck
• Lung Squamous Cell Carcinoma Stage IV
• Anal Squamous Cell Carcinoma
• Carcinoma, Non-Small-Cell Lung

Inclusion Criteria:

• Must be appropriate candidate for experimental therapy, as determined by investigator, after available standard therapies have failed
• Have adequate organ function
• Prior Therapies: Systemic treatments: must have discontinued previous systemic treatments for cancer and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy at least 42 days and have discontinued any cytotoxic therapies at least 28 days prior to study enrollment. Radiation therapy and surgery: must be completed at least 4 weeks before study enrollment
• Part A: Must have diagnosis of cancer that is advanced or metastatic
• Part B: Must have histologically confirmed squamous cell cancer of the head and neck or must have squamous cell cancer of any tumor type
• Part C: Must have histological diagnosis of squamous cell cancer of the head and neck, histological or cytological diagnosis of squamous non-small-cell lung cancer, or histological diagnosis of Stage IIIB (N2 or N3) or Stage IV small cell cancer of the anus that is not curable by local therapy
• Must be available during the duration of the study and willing to follow the study procedures
• If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for three months following the last dose of study drug
• If the participant is a female of childbearing potential, must have had a negative serum or urine pregnancy test within 7 days of the first dose of study drug and must not be breast feeding

Exclusion Criteria:

• Must not have taken an unapproved drug as treatment for any indication within the last 28 days prior to starting study treatment
• Must not have an active symptomatic fungal, bacterial or viral infection, including human immunodeficiency virus (HIV) or Hepatitis A, B, or C
• Must not have a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
• Must not have systolic blood pressure <90 millimeters of mercury (mmHg) or recurrent symptomatic orthostatic hypotension
• Must not have a family history of long QTc syndrome or be taking drugs known to cause QTc prolongation or Torsades de Pointes
• Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome
• Must not have acute leukemia