A Study of LY2880070 in Participants With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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The main purpose of this 3-part study is to evaluate the safety and efficacy of the study drug known as LY2880070 in participants with advanced or metastatic solid tumors.

Official Title
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A Phase 1b/2a Three-Part Open-Label Multicenter Study to Evaluate the Safety and Efficacy of LY2880070 as Monotherapy and in Combination With Gemcitabine in Patients With Advanced or Metastatic Cancer

Conditions
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Ovarian Cancer, Colon Cancer, Rectal Cancer, Neoplasms, Endometrial Cancer, Soft Tissue Sarcoma, Triple Negative Breast Cancer, Pancreas Cancer, Solid Tumors, Colorectal Cancer, Breast Cancer, Pancreatic Cancer

Intervention / Treatment
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* Drug: LY2880070
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Have an estimated life expectancy of greater than or equal to (≥)12 weeks Have adequate organ function Have received 1-4 prior systemic therapies for locally advanced or metastatic disease Agree to use medically approved contraceptives during the study and for 3 months following the last study treatment All females must have a negative serum pregnancy test result, and females of child-bearing potential must have a negative urine pregnancy test result, prior to the first study treatment Have tumor lesions considered measurable by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Must be, in the judgment of the investigator, an appropriate candidate for experimental therapy, and no standard therapy would confer clinical benefit For Part A Must have evidence of cancer (solid tumors, excluding glioblastoma and primary brain tumor) that is advanced or metastatic For the Metabolism Phenotype Arm in Part A, participants must have a Cytochrome P450 (CYP2D6) poor metabolizer phenotype For Part B Have advanced or metastatic colorectal cancer, triple negative breast cancer (per American Society of Clinical Oncology-College of American Pathology guidelines), epithelial ovarian cancer, endometrial, soft tissue sarcoma, pancreatic cancer For TNBC: Recurrent/refractory Triple Negative Breast Cancer (TNBC) defined as any beast cancer that expresses <1% estrogen receptor (ER) and <1% progesterone receptor (PR) and is Her2 negative For Colorectal (CRC): Must have histologically confirmed advanced or metastatic colorectal cancer For Ovarian Cancer: Must have histologically confirmed advanced or metastatic epithelial ovarian cancer Must be eligible to receive Gemzar (GEM) and not refractory to GEM/carboplatin Must have the ability to tolerate GEM May have received GEM as previous therapy For Endometrial cancer: Must have histologically confirmed endometrial cancer that is metastatic or locally advanced Must have failed at least 1 prior chemotherapy For STS: Must have histologically confirmed STS that is metastatic or locally advanced Patients with gastrointestinal stromal tumors (GIST) must have failed a KIT inhibitor Must have failed at least 1 prior chemotherapy For Pancreatic Cancer: Must have histologically confirmed pancreatic cancer that is metastatic or locally advanced Must have failed at least 1 prior chemotherapy regimen For Part C Participants with high grade serous ovarian cancer (HGSOC) will be screened for specific genetic signatures Exclusion Criteria: Have received treatment with an investigational drug which has not received regulatory approval within 21 days of first study treatment Have symptomatic central nervous system (CNS) metastasis Females who are pregnant or nursing Have known positive test results of human immunodeficiency virus, or have chronic active hepatitis A, B or C Have a corrected QT interval (QTcB) greater than (>) 470 milliseconds (msec) (female) or >450 msec (male), or a history of congenital long QT syndrome Have had a bone marrow transplant Have participated in this study, or are currently enrolled in another clinical study of an investigational medicinal product Have had radiation therapy to >25% of bone marrow For Part B Have a history of another active cancer within the past year, except cervical cancer in situ, in situ carcinoma of the bladder, basal cell carcinoma of the skin, or another in situ carcinoma that is considered cured

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: LY2880070<br>Multiple oral doses of LY2880070 during 21-day cycles | Drug: LY2880070<br>* Capsules<br>|
| Experimental: Part A: LY2880070 with Gemcitabine<br>Multiple oral doses of LY2880070, and Gemcitabine administered intravenously during 21-day cycles | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part A: LY2880070 (Metabolism Phenotype)<br>Multiple oral doses of LY2880070 administered during 21 day cycles, to participants who are poor metabolizers | Drug: LY2880070<br>* Capsules<br>|
| Experimental: Part B: LY2880070 and Gemcitabine (Breast)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part B: LY2880070 and Gemcitabine (Colorectal)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part B:LY2880070 and Gemcitabine (Ovarian)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part B: LY2880070 and Gemcitabine (Endometrial)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part B: LY2880070 and Gemcitabine (Soft Tissue Sarcoma (STS))<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part B: LY2880070 and Gemcitabine (Pancreatic)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|
| Experimental: Part C: LY2880070 and Gemcitabine (High Grade Serous Ovarian Cancer)<br>Multiple oral doses of LY2880070 during 21-day cycles with Gemcitabine (administered intravenously) | Drug: LY2880070<br>* Capsules<br>Drug: Gemcitabine<br>* 50 to 600 milligrams per square meter of body surface area (mg/m2)<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose(s) |  | Baseline through Cycle 1 (Estimated up to 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of dose limiting toxicities (DLTs) |  | Baseline through Cycle 1 (Estimated up to 21 days) | 
| Area under the plasma concentration versus time curve from time zero to 24 hours post-dose (AUC0-24) |  | Baseline to 24-hours post dose (up to Day 20 in Cycle 1) | 
| Peak plasma concentration (Cmax) |  | Baseline to 24 hours post-dose (up to Day 20 in Cycle 1) | 
| Time to reach maximum plasma concentration (tmax) |  | Baseline to 24 hours post dose (up to Day 20 in Cycle 1) | 
| Change from baseline in white blood cell count |  | Baseline to 24 hours post dose (up to Day 20 in Cycle 1) | 
| Change from baseline in neutrophil count |  | Baseline to 24 hours post dose (up to Day 20 in Cycle 1) | 
| Change from baseline in lymphocyte count |  | Baseline to 24 hours post dose (up to Day 20 in Cycle 1) | 
| Number of participants with tumor response (objective response rate) as measured by the Response Evaluable Criteria in Solid Tumors (RECIST v.1.1) |  | Baseline to study completion (estimated up to 4 years) | 
| Duration of objective response |  | Baseline to study completion (estimated up to 4 years) | 
| Best response |  | Baseline to study completion (estimated up to 4 years) | 
| Progression free survival |  | Baseline to study completion (estimated up to 4 years) | 
| Overall survival |  | Baseline up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic cancer, Advanced cancer, Recurrent cancer, Colorectal neoplasms, Triple negative breast cancer, Ovarian neoplasms, Colon neoplasms, Rectal neoplasms, Triple negative breast neoplasms, Gastrointestinal stromal tumor, Pancreatic Neoplasms, Pancreatic Cancer