A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors
Status and phase
Terminated
Phase 1
Conditions
Solid Tumor
Breast Cancer
Soft Tissue Sarcoma
Colon Cancer
Cholangiocarcinoma
Treatments
Drug: Carboplatin
Drug: Cisplatin
Drug: Abemaciclib
Drug: Taladegib
Drug: Gemcitabine
Drug: LY3039478
Drug: LY3023414
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
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.
Enrollment
94 patients
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
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.
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
94 participants in 12 patient groups
Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1)
Experimental group
Description:
25 mg LY3039478 given orally 3 times per week (TIW) in combination with 200 mg taladegib given orally once daily (QD) on a 28 day cycle. A single dose of 200 mg taladegib was also be given on day 1 during a 3-day lead-in period for pharmacokinetic (PK) evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Taladegib
Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3023414
Drug: LY3039478
Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2)
Experimental group
Description:
50 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3023414
Drug: LY3039478
Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 200 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 200 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3023414
Drug: LY3039478
Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3023414
Drug: LY3039478
Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 100 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 100 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Abemaciclib
Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2)
Experimental group
Description:
50 mg LY3039478 given orally TIW in combination with 100 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 100 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Abemaciclib
Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 150 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 150 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Abemaciclib
Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 25 mg/m2 cisplatin and 1000 mg/m2 gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Gemcitabine
Drug: Cisplatin
Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2)
Experimental group
Description:
50 mg LY3039478 given orally TIW in combination with 25 mg/m2 cisplatin and1000 mg/m2 gemcitabine given as IV infusions on days 1 and 8 of a 21 day cycle.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Gemcitabine
Drug: Cisplatin
Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1)
Experimental group
Description:
25 mg LY3039478 given orally TIW in combination with 1000 mg/m2 gemcitabine and area under the plasma concentration-time curve dose of (AUC) carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Gemcitabine
Drug: Carboplatin
Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2)
Experimental group
Description:
50 mg LY3039478 given orally TIW in combination with 1000 mg/m2 gemcitabine and AUC dose of carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.
Participants receiving benefit may continue until disease progression.
Treatment:
Drug: LY3039478
Drug: Gemcitabine
Drug: Carboplatin
Trial contacts and locations
11
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Data sourced from clinicaltrials.gov
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