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

Lilly

Status and phase

Completed

Phase 1

Conditions

Solid Tumor

Breast Cancer

Soft Tissue Sarcoma

Colon Cancer

Cholangiocarcinoma

Treatments

Drug: Cisplatin

Drug: Taladegib

Drug: Carboplatin

Drug: LY3039478

Drug: LY3023414

Drug: Abemaciclib

Drug: Gemcitabine

Study type

Interventional

Funder types

Industry

Identifiers

NCT02784795

16209

2015-004421-14 (EudraCT Number)

I6F-MC-JJCD (Other Identifier)

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 5 patient groups

LY3039478 + Taladegib

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Taladegib

LY3039478 + LY3023414

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: LY3023414

LY3039478 + Abemaciclib

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Abemaciclib

LY3039478 + Cisplatin/Gemcitabine

Experimental group

Description:

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.

Treatment:

Drug: LY3039478

Drug: Cisplatin

Drug: Gemcitabine

LY3039478 + Gemcitabine/Carboplatin