A Study of LY3039478 in Participants With Advanced Cancer

Lilly

Status and phase: Completed; Phase 1

Conditions: Neoplasms; Lymphoma; Neoplasm Metastasis

Treatments: Drug: Prednisone; Drug: LY3039478

Study type: Interventional

Funder types: Industry

Identifiers

NCT01695005

14547

I6F-MC-JJCA (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to find a recommended dose level of LY3039478 that can safely be taken by participants with advanced cancer or cancer that has spread to other parts of the body, including but not limited to lymphoma. The study will also explore changes to various markers in blood cells and tissue. Finally, the study will help to document any tumor activity this drug may have.

Full description

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E. In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level. Participants in Part B and D must have a defined alteration in a certain molecular pathway. Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part F participants will receive increasing doses of LY3039478 in combination with prednisone to define the maximum tolerated dose level.

Enrollment: 247 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 (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.

• For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway.

• For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma.

• For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway.

• Cohort 1: Participants must have triple negative breast cancer.

• Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A.

• Cohort 3: Participants must have cholangiocarcinoma.

• Cohort 4: Participants must have chronic lymphocytic leukemia.

• Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell neoplasm.

• For Part E: Participants must have adenoid cystic carcinoma (ACC).

• For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway.

• As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro Oncology (RANO) criteria for glioblastoma:

  • For Dose Escalation (Part A): Have measurable or nonmeasurable disease.
  • For Parts B, C, D, E and F: Have measurable disease or reliable biomarker measure.

• For Parts B, C, D, E and F: Have available tumor tissue.

• Have adequate organ function.

• Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy of more than 12 weeks.

Exclusion criteria

• Have symptomatic or non stable central nervous system (CNS) malignancy.

• Females who are pregnant or lactating.

• Have active bacterial, fungal, and/or known viral infection.

• Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic).

• Participants with HCC that:

  • Have known HCC with fibro-lamellar or mixed histology.
  • Have presence of clinically relevant ascites.
  • Have had a liver transplant.
  • Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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247 participants in 4 patient groups

LY3039478 - Dose Escalation

Experimental group

Description:

Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams \[mg\], 5 mg, 10 mg, 20 mg, 30 mg, 45 mg, 60 mg, 75 mg and 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression

Treatment:

Drug: LY3039478

LY3039478 - Cohort Expansion

Experimental group

Description:

Part B,C,D \& E:LY3039478 administered orally three times per week(TIW) at a fixed dose determined in Part A for two 28 day cycles.Participants receiving benefit may continue until disease progression.The doses administered were as follows:Part B:50 mg or 75 mg for participants(pts) who had tumors with molecular alterations related to the Notch pathway;Part C:50 mg or 75 mg for pts who had Leiomyosarcoma(LMS),50 mg or 75 mg for pts who had other Sarcoma, 50 mg for pts who had gastrointestinal stromal tumors(GIST);Part D: 75 mg for pts in the Triple Negative Breast Cancer cohort,75 mg for pts in Cholangiocarcinoma cohort,50 mg for pts in Triple Negative Breast Cancer cohort,50 mg for pts in the Hepatocellular Carcinoma cohort,50 mg for pts in the Cholangiocarcinoma cohort, 50 mg for pts in the Chronic lymphocytic leukemia(CLL) cohort, 50 mg for pts in the Mature T cell, B cell or Natural Killer(NK) cell neoplasms cohort; Part E: 50 mg for pts in the Triple Negative Breast Cancer cohort.

Treatment:

Drug: LY3039478

Dose 1 LY3039478 + Prednisone

Experimental group

Description:

Part F1: Participants received a loading dose of 75 mg or 100 mg administered 3 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.

Treatment:

Drug: LY3039478

Drug: Prednisone

Dose 2 LY3039478 + Prednisone

Experimental group

Description:

Part F2: Participants received a loading dose of 75 mg, 100 mg or 125 mg 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.

Treatment:

Drug: LY3039478

Drug: Prednisone