Solid TumorPhase 1NCT02784795
A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors
A Phase 1 study testing LY3039478, Taladegib and Abemaciclib in people with Solid Tumor and Breast Cancer, run by Eli Lilly and Company at 11 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Breast Cancer, Colon Cancer
- What is being tested?
- LY3039478, Taladegib and Abemaciclib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 94 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 4 Nov 2016to 13 Feb 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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 locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States4 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
France3 sites
Institut Bergonie
Bordeaux, 33076
Centre Leon Berard
Lyon, 69373
Gustave Roussy
Villejuif, 94805
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Fundacion Jimenez Diaz
Madrid, 28040
Hospital Madrid Norte Sanchinarro
Madrid, 28050
About this study
Official title: A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
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.
- Being tested
- LY3039478, Taladegib, Abemaciclib, Cisplatin, Gemcitabine
- Keywords
- Notch Inhibitor
- Medical subject headings
- Breast Neoplasms, Colonic Neoplasms, Cholangiocarcinoma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3039478Drug
Administered orally
TaladegibDrug
Also called LY2940680
Administered orally
AbemaciclibDrug
Also called LY2835219
Administered orally
CisplatinDrug
Administered IV
GemcitabineDrug
Administered IV
CarboplatinDrug
Administered IV
LY3023414Drug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1) | Experimental | 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. Receives: Drug: LY3039478; Drug: Taladegib |
| Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation) | Experimental | 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. Receives: Drug: LY3039478; Drug: LY3023414 |
| Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2) | Experimental | 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. Receives: Drug: LY3039478; Drug: LY3023414 |
| Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3) | Experimental | 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. Receives: Drug: LY3039478; Drug: LY3023414 |
| Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation) | Experimental | 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. Receives: Drug: LY3039478; Drug: LY3023414 |
| Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1) | Experimental | 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. Receives: Drug: LY3039478; Drug: Abemaciclib |
| Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2) | Experimental | 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. Receives: Drug: LY3039478; Drug: Abemaciclib |
| Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3) | Experimental | 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. Receives: Drug: LY3039478; Drug: Abemaciclib |
| Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1) | Experimental | 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. Receives: Drug: LY3039478; Drug: Cisplatin; Drug: Gemcitabine |
| Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2) | Experimental | 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. Receives: Drug: LY3039478; Drug: Cisplatin; Drug: Gemcitabine |
| Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1) | Experimental | 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. Receives: Drug: LY3039478; Drug: Gemcitabine; Drug: Carboplatin |
| Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2) | Experimental | 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. Receives: Drug: LY3039478; Drug: Gemcitabine; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With LY3039478 Dose-Limiting Toxicities (DLT) in Part A, B, C, D and E
DLT is defined as an adverse event (AE) during Cycle 1 (28 days for Part A, B and C and 21 days for Part D, E) that was possibly related to the study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: ≥Grade 3 non-hematological toxicity except nausea/vomiting, diarrhea, or constipation that can be controlled with appropriate care; Grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) lasting fewer than 8 days (without evidence of other hepatic injury); Grade 3 rash that resolves or improves to a Grade 2 or less within 7 days; CTCAE Grade 4 hematological toxicity of >5 days duration; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia with bleeding; Grade 3 febrile neutropenia.
Measured: Baseline to toxicity (up to end of Cycle 1 [1Cycle = 28 days for Part A, B and C and 21 days for Part D, E])
Secondary outcomes (8)
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478 in Combination With Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin in Part A, B, C, D and E
AUC[0-∞] of LY3039478 in combination with taladegib, LY3023414, abemaciclib, cisplatin/gemcitabine, and gemcitabine/carboplatin in dose escalation parts of Part A, B, C, D and E was evaluated.
Measured: Parts A/B/C Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30 hours post-dose; Parts D/E Day 1 (Cycle 1) and 15 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6-8, 24-30 hours post-dose
PK: AUC[0-∞] of Taladegib and Its Active Metabolite LSN3185556, in Combination With LY3039478 (Part A)
AUC[0-∞] of taladegib and its active metabolite LSN3185556, in combination with LY3039478 (Part A) was evaluated.
Measured: Day -3 (Lead in) : pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose and Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day -3 (Part B)
AUC[0-∞] of LY3023414 in combination with LY3039478 (Part B) on day -3 was evaluated.
Measured: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day 22 (Part B)
AUC[0-∞] of LY3023414 in combination with LY3039478 (Part B) on day 22 was evaluated. LY3023414 PK data is summarized only for dose escalation patients in Part B with intensive PK sampling.
Measured: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day -3 (Part C)
AUC[0-∞] of abemaciclib and AUC[0-tlast] of its major active metabolites LSN2839567 and LSN3106726, in combination with LY3039478 on Day 3 (Part C) was evaluated.
Measured: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day 22 (Part C)
AUC[0-∞] of abemaciclib and AUC[0-tlast] of its major active metabolites LSN2839567 and LSN3106726, in combination with LY3039478 on Day 22 (Part C) was evaluated.
Measured: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
Duration of Response (DoR)
DoR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date.
Measured: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Up To 12 Months)
Progression Free Survival (PFS) Time in Part A, B, C, D and E
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. PFS time was summarized using Kaplan-Meier estimates.
Measured: Baseline to Objective Disease Progression or Death (Up To 1.91 Months for Part A, 7.69 Months for Part B, 11.53 Months for Part C, 19.52 Months for Part D, 7.03 Months for Part E)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2016 (estimated)
- Study start4 Nov 2016
- Primary completion9 Aug 2018
- Study completion13 Feb 2020
Why it stopped: The study was terminated due to business considerations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- As per the study protocol design description, the study was conducted as multicenter, nonrandomized, open-label, Phase 1b study consisting of 5 separate, parallel dose escalations in patients with advanced/metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in specified tumor types.
- Masking
- None (open label)
- Enrolment
- 94 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02784795
- Sponsor's protocol ID
- 16209
- Other IDs
- I6F-MC-JJCD, 2015-004421-14, 2015
- Status last verified
- Aug 2025
- First submitted
- 25 May 2016
- Last updated
- 21 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 36030462Azaro 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.
PubMed 33686452
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT02784795
- Acronym / sponsor ID
- 16209
- Keywords
- Notch Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to business considerations
- Enrolment
- 94 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2016 (actual)
- Primary completion
- 9 Aug 2018 (actual)
- Study completion
- 13 Feb 2020 (actual)
- First posted
- 27 May 2016 (estimated)
- Results
- Posted 21 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 12
- Model description
- As per the study protocol design description, the study was conducted as multicenter, nonrandomized, open-label, Phase 1b study consisting of 5 separate, parallel dose escalations in patients with advanced/metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in specified tumor types.
| Arm | Type | Receives |
|---|---|---|
| Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1) | Experimental | Drug: LY3039478, Drug: Taladegib25 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. |
| Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation) | Experimental | Drug: LY3039478, Drug: LY302341425 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. |
| Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2) | Experimental | Drug: LY3039478, Drug: LY302341450 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. |
| Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3) | Experimental | Drug: LY3039478, Drug: LY302341425 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. |
| Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation) | Experimental | Drug: LY3039478, Drug: LY302341425 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. |
| Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1) | Experimental | Drug: LY3039478, Drug: Abemaciclib25 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. |
| Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2) | Experimental | Drug: LY3039478, Drug: Abemaciclib50 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. |
| Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3) | Experimental | Drug: LY3039478, Drug: Abemaciclib25 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. |
| Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1) | Experimental | Drug: LY3039478, Drug: Cisplatin, Drug: Gemcitabine25 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. |
| Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2) | Experimental | Drug: LY3039478, Drug: Cisplatin, Drug: Gemcitabine50 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. |
| Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1) | Experimental | Drug: LY3039478, Drug: Gemcitabine, Drug: Carboplatin25 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. |
| Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2) | Experimental | Drug: LY3039478, Drug: Gemcitabine, Drug: Carboplatin50 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY3039478Administered orally | Drug | Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1), Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation), Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation), Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3), Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2), Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1), Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3), Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2), Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2), Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1), Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1), Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2) |
| TaladegibAlso: LY2940680Administered orally | Drug | Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1) |
| AbemaciclibAlso: LY2835219Administered orally | Drug | Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1), Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3), Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2) |
| CisplatinAdministered IV | Drug | Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2), Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1) |
| GemcitabineAdministered IV | Drug | Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2), Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1), Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1), Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2) |
| CarboplatinAdministered IV | Drug | Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1), Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2) |
| LY3023414Administered orally | Drug | Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation), Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation), Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3), Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2) |
Primary outcome
Number of Participants With LY3039478 Dose-Limiting Toxicities (DLT) in Part A, B, C, D and E
Time frame: Baseline to toxicity (up to end of Cycle 1 [1Cycle = 28 days for Part A, B and C and 21 days for Part D, E])
DLT is defined as an adverse event (AE) during Cycle 1 (28 days for Part A, B and C and 21 days for Part D, E) that was possibly related to the study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: ≥Grade 3 non-hematological toxicity except nausea/vomiting, diarrhea, or constipation that can be controlled with appropriate care; Grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) lasting fewer than 8 days (without evidence of other hepatic injury); Grade 3 rash that resolves or improves to a Grade 2 or less within 7 days; CTCAE Grade 4 hematological toxicity of >5 days duration; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia with bleeding; Grade 3 febrile neutropenia.
8 secondary outcomes
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478 in Combination With Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin in Part A, B, C, D and E
Time frame: Parts A/B/C Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30 hours post-dose; Parts D/E Day 1 (Cycle 1) and 15 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6-8, 24-30 hours post-dose
PK: AUC[0-∞] of Taladegib and Its Active Metabolite LSN3185556, in Combination With LY3039478 (Part A)
Time frame: Day -3 (Lead in) : pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose and Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day -3 (Part B)
Time frame: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day 22 (Part B)
Time frame: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day -3 (Part C)
Time frame: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day 22 (Part C)
Time frame: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
Duration of Response (DoR)
Time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Up To 12 Months)
Progression Free Survival (PFS) Time in Part A, B, C, D and E
Time frame: Baseline to Objective Disease Progression or Death (Up To 1.91 Months for Part A, 7.69 Months for Part B, 11.53 Months for Part C, 19.52 Months for Part D, 7.03 Months for Part E)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36030462Massard 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.
- Derived from this study: PubMed 33686452Azaro 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3039478, Taladegib and Abemaciclib in people with Solid Tumor and Breast Cancer, run by Eli Lilly and Company at 11 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, France, Spain, Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With LY3039478 Dose-Limiting Toxicities (DLT) in Part A, B, C, D and E (time frame: Baseline to toxicity (up to end of Cycle 1 [1Cycle = 28 days for Part A, B and C and 21 days for Part D, E])). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02784795, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025.