A Study of Prexasertib (LY2606368) With Chemotherapy or Targeted Agents in Participants With Advanced Cancer

The main purpose of this study is to investigate the safety of prexasertib in combination with other anti-cancer drugs (cisplatin, cetuximab, pemetrexed, fluorouracil or LY3023414) in participants with advanced cancer or cancer that has spread to another part of the body. The study has multiple parts (A, B, C, D and E). Participants will only enroll in one part.

The primary purpose of Parts A, B, C, D and E of this study is to determine a recommended dose level and schedule of prexasertib (an inhibitor of checkpoint kinase 1 and 2 \[CHK1/CHK2\] in combination with:

* cisplatin (Part A)
* cetuximab (Part B)
* pemetrexed (Part C)
* fluorouracil (Part D)
* LY3023414 (Part E) \[An inhibitor of phosphoinositide 3-kinase alpha (PI3K alpha) and mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), and other class I phosphoinositide 3-kinase (PI3K) family members\]

in participants with advanced or metastatic cancer.

Part A dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cisplatin in participants with advanced or metastatic cancer, Part B dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with cetuximab in participants with advanced or metastatic colorectal cancer, Part C and D dose expansions have been removed and Part E dose expansion of the study will evaluate the safety and toxicity of prexasertib at the recommended dose level in combination with LY3023414 in participants with advanced or metastatic cancer, participants with PIK3CA mutations, or with advanced or metastatic breast cancer.

In Parts A and B the effect of adding granulocyte colony stimulating factor (G-CSF) to cisplatin in combination with prexasertib and cetuximab in combination with prexasertib will be explored. In Part A the effect of changing the schedule of prexasertib and cisplatin also will be explored. In Part B the effect of changing the schedule of prexasertib and cetuximab also will be explored.

Eligibility Criteria:
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
* All parts except Part B, Part E2, and Part E3 dose expansion: Must have diagnosis of cancer that is advanced or metastatic
* Part B dose expansion: Must have confirmed Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type colorectal cancer that is metastatic or recurrent and has failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant of irinotecan or oxaliplatin
* Part E2 dose expansion: must have cancer that is advanced or metastatic and have prior documentation of a mutation of PIK3CA
* Part E3 dose expansion: must have advanced or metastatic ER-negative, PR-negative, and HER-2 non-overexpressing breast cancer
* Must be available during the duration of the study and willing to follow the study procedures
* Parts A and B: If participant is of reproductive potential, must agree to use medically approved contraceptive precautions during the study and for six months following the last dose of study drug
* Parts C, D and E: 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 14 days of the first dose of study drug and must not be breast feeding
* Part E: Are able to swallow capsules or tablets

Exclusion Criteria:

* Have received more than 2 previous lines of cytotoxic chemotherapy (if receiving cisplatin, 5-FU or pemetrexed)
* 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 a family history of long QTc syndrome
* Must not have a serotonin-secreting carcinoid tumor or a prior history of drug-induced serotonin syndrome
* Must not have acute leukemia
* Part E: Have insulin-dependent (type I) diabetes or a history of gestational diabetes
* Part E: Prior treatment with a PI3K/mTOR inhibitor