A Study in Ovarian, Non-Small Cell Lung, Prostate, Colorectal, Gastroesophageal Cancers, and Squamous Cell Carcinoma of the Head and Neck

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to estimate the rate of response for patients with ovarian, non-small cell lung, prostate, colorectal, gastroesophageal, and head and neck cancers who are administered LY2523355.

Official Title
-----------------
A Phase 2 Indication Identification Study of LY2523355 in Patients With Ovarian, Non-Small Cell Lung, Prostate, Colorectal, Gastroesophageal Cancers, and Squamous Cell Carcinoma of the Head and Neck

Conditions
-----------------
Ovarian Cancer, Non Small Cell Lung Cancer, Prostate Cancer, Colorectal Cancer, Gastric Cancer, Esophageal Cancer, Cancer of Head and Neck

Intervention / Treatment
-----------------
* Drug: LY2523355
* Drug: pegfilgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of ovarian, non-small cell lung, prostate, colorectal, gastroesophageal cancer (adenocarcinoma of the esophageal cancer, stomach, or gastroesophageal junction), or squamous cell cancer of the head and neck Have measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines (except prostate cancer participants) Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Are willing to follow study procedures for the duration of the study Are willing to use an approved contraceptive method during treatment and for 3 months after discontinuation of study treatment Exclusion Criteria: Have a serious preexisting medical condition that would preclude participation in the study Are pregnant or lactating Have received treatment within 28 days of first dose of LY2523355 with a drug that has not received regulatory approval for any indication Have symptomatic, untreated, or uncontrolled central nervous system (CNS) metastases Have a second active primary malignancy or a history of a second malignancy requiring cytotoxic therapy Have QTc interval greater than 470 millisecond (msec) or intraventricular conduction delay (IVCD) with QRS greater than 120 msec on screening electrocardiogram (ECG) Have active symptomatic fungal, bacterial, and/or known viral infection including active human immunodeficiency virus (HIV) or viral (A, B, C) hepatitis Participants with pneumonia, evidence of obstructive pneumonitis, other respiratory infections, or infection from other sources are to be excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2523355<br> | Drug: LY2523355<br>* Dose determined by participant body surface area: 5 milligrams/square meter(mg/m²) or 6 mg/m², administered intravenously as a 1-hour infusion on Days 1, 2 and 3 of a 21 day cycle; for up to 2 cycles (4 cycles for prostate cancer patients). Additional cycles administered based on patient response assessment.<br>Drug: pegfilgrastim<br>* 6 milligrams (mg), administered subcutaneously approximately 24 hours after third dose of LY2523355 on Day 4 of each 21-day cycle, for up to 2 cycles of LY2523355 administration (4 cycles for prostate cancer patients). Additional cycles of LY2523355 administered based on patient response assessment.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | The percentage of participants who achieved a best response of either CR or PR, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. Percentage is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. | Baseline until progressive disease up to 36 weeks post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS defined as the time from date of first dose to the first observation of disease progression or death due to any cause. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 millimeter (mm) increase over nadir. For participants who were not known to have died or to have progressed as of the data inclusion cutoff date, PFS were censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. | Date of enrollment to progressive disease or death due to any cause up to 36 weeks post-enrollment | 
| Percentage of Participants Who Achieved a Best Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) | Response using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. PR was defined as at least a 30% decrease in sum of longest diameter of target lesions and for prostate cancer PR was defined as a ≥50% decrease in baseline prostate-specific antigen (PSA) value that was confirmed with a second value ≥3 weeks later. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir. SD was defined as small changes that did not meet above criteria. | Baseline until progressive disease up to 36 weeks post-baseline | 
| Tumor Marker Values as Relevant to Specific Tumor Types at Baseline | The number of participants with colorectal cancer (CRC), gastroesophageal cancer (GE), non-small cell lung cancer (NSCLC), ovarian cancer, prostate cancer or squamous cell carcinoma of head and neck (SCCHN) who had marker/molecular diagnostics performed prior to study entry to determine the mutation status of cancer genes: APC, BRAF, BRCA1, BRCA2, HRAS and KRAS and the presence of Human Papillovirus (HPV) and Epstein Barr viruses (EBV). Mutation/virus status was defined as: positive (mutation/virus present), negative (mutation/virus not present), unknown (mutation/virus status unknown), or not done (mutation/virus status was not done). | Baseline | 
| Change in Tumor Size at Smallest Size (Best Response) | The percent change in tumor size at its smallest size. The sum of diameters of target lesions was determined at each tumor assessment. The percent change is the smallest post-baseline sum divided by the baseline (pre-treatment) sum, multiplied by 100. | Baseline until cycle with maximum change from baseline up to 36 weeks | 
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) of LY2523355 and Metabolite LSN2546307 | Plasma Cmax following daily doses of LY2523355 on Days 1, 2, and 3 of Cycle 1 (21-day cycle). | Day 3 of Cycle 1 (21-day cycle) | 
| Pharmacokinetics, Intracycle Accumulation Ratio (Ra) of LY2523355 | Intracycle Ra of LY2523355 is the ratio of LY2523355 maximum plasma concentration (Cmax) on Day 3 of Cycle 1 to the Cmax of LY2523355 on Day 1 of Cycle 1 following daily doses of LY2523355 on Days 1, 2 and 3 of Cycle 1 (21-day cycle) at each dose level. | Day 1 and Day 3 of Cycle 1 (21-day cycle) |