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

NCT ID: NCT02784795

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-04
• Study Completion Date: 2020-02-13

Brief Summary

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.

Conditions

Solid Tumor; Breast Cancer; Colon Cancer; Cholangiocarcinoma; Soft Tissue Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Taladegib

Intervention Type: DRUG

Administered orally

Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

LY3023414

Intervention Type: DRUG

Administered orally

Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

LY3023414

Intervention Type: DRUG

Administered orally

Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

LY3023414

Intervention Type: DRUG

Administered orally

Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

LY3023414

Intervention Type: DRUG

Administered orally

Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Abemaciclib

Intervention Type: DRUG

Administered orally

Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Abemaciclib

Intervention Type: DRUG

Administered orally

Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Abemaciclib

Intervention Type: DRUG

Administered orally

Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Cisplatin

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Cisplatin

Intervention Type: DRUG

Administered IV

Gemcitabine

Intervention Type: DRUG

Administered IV

Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Gemcitabine

Intervention Type: DRUG

Administered IV

Carboplatin

Intervention Type: DRUG

Administered IV

Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2)

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.

Group Type: EXPERIMENTAL

LY3039478

Intervention Type: DRUG

Administered orally

Gemcitabine

Intervention Type: DRUG

Administered IV

Carboplatin

Intervention Type: DRUG

Administered IV

Interventions

LY3039478

Administered orally

Intervention Type: DRUG

Taladegib

Administered orally

Intervention Type: DRUG

Abemaciclib

Administered orally

Intervention Type: DRUG

Cisplatin

Administered IV

Intervention Type: DRUG

Gemcitabine

Administered IV

Intervention Type: DRUG

Carboplatin

Administered IV

Intervention Type: DRUG

LY3023414

Administered orally

Intervention Type: DRUG

Other Intervention Names

LY2940680; LY2835219

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Rigshospitalet

Copenhagen, København Ø, Denmark

Institut Bergonie

Bordeaux, , France

Centre Leon Berard

Lyon, , France

Gustave Roussy

Villejuif, , France

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Madrid Norte Sanchinarro

Madrid, , Spain

Countries

United States; Denmark; France; Spain

References

Massard C, Cassier PA, Azaro A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors. Cancer Chemother Pharmacol. 2022 Oct;90(4):335-344. doi: 10.1007/s00280-022-04461-z. Epub 2022 Aug 28.

Reference Type: DERIVED

PMID: 36030462 (View on PubMed)

Azaro A, Massard C, Tap WD, Cassier PA, Merchan J, Italiano A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors. Invest New Drugs. 2021 Aug;39(4):1089-1098. doi: 10.1007/s10637-021-01094-6. Epub 2021 Mar 8.

Reference Type: DERIVED

PMID: 33686452 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://lillytrialguide.com/en/studies/solid-tumor/JJCD#?postal=

Click here for more information about this study:A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors

Other Identifiers

I6F-MC-JJCD

Identifier Type: OTHER

Identifier Source: secondary_id

2015-004421-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

16209

Identifier Type: -

Identifier Source: org_study_id