A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors.

Official Title
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A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Solid Tumor, Breast Cancer, Colon Cancer, Cholangiocarcinoma, Soft Tissue Sarcoma

Intervention / Treatment
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* Drug: LY3039478
* Drug: Taladegib
* Drug: Abemaciclib
* Drug: Cisplatin
* Drug: Gemcitabine
* Drug: Carboplatin
* Drug: LY3023414


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer. For dose escalation for all combinations: The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic. For Part A dose confirmation: All participants must have histological evidence of advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >1 line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease). For Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >2 lines of systemic treatment for advanced or metastatic TNBC. Have adequate organ function. Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. Have discontinued all previous therapies for cancer. Exclusion Criteria: Have current acute leukemia. Have current or recent (within 3 months of study drug administration) gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3039478 + Taladegib<br>LY3039478 given orally 3 times per week (TIW) in combination with taladegib given orally daily on a 28 day cycle. A single dose of taladegib will also be given on day 1 during a 3-day lead-in period. | Drug: LY3039478<br>* Administered orally<br>Drug: Taladegib<br>* Administered orally<br>* Other names: LY2940680;|
| Experimental: LY3039478 + LY3023414<br>LY3039478 given orally TIW in combination with LY3023414 given orally every 12 hours on a 28-day cycle. A single dose of LY3023414 will also be given on day 1 during a 3-day lead-in period. | Drug: LY3039478<br>* Administered orally<br>Drug: LY3023414<br>* Administered orally<br>|
| Experimental: LY3039478 + Abemaciclib<br>LY3039478 given orally TIW in combination with abemaciclib given orally every 12 hours on a 28-day cycle. A single dose of abemaciclib will also be given on day 1 during a 3-day lead-in period. | Drug: LY3039478<br>* Administered orally<br>Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;|
| Experimental: LY3039478 + Cisplatin/Gemcitabine<br>LY3039478 given orally TIW in combination with cisplatin and gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle. | Drug: LY3039478<br>* Administered orally<br>Drug: Cisplatin<br>* Administered IV<br>Drug: Gemcitabine<br>* Administered IV<br>|
| Experimental: LY3039478 + Gemcitabine/Carboplatin<br>LY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle. | Drug: LY3039478<br>* Administered orally<br>Drug: Gemcitabine<br>* Administered IV<br>Drug: Carboplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of LY3039478 |  | Cycle 1 (up to 28 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve (AUC) of LY3039478 in Combination with Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin |  | Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles) | 
| PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478 |  | Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles) | 
| PK: AUC of LY3023414 in Combination with LY3039478 |  | Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles) | 
| PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478 |  | Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles) | 
| Duration of Response (DoR) |  | Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Estimated up to 12 Months) | 
| Progression Free Survival (PFS) |  | Baseline to Objective Disease Progression or Death (Estimated up to 12 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Notch Inhibitor