Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
LY3039478 · 3 trials · 6 indications
DLT was defined as an adverse event (AE) that occurred during Cycle 1 (first 28 days) related to the study drug and met one of the following criteria per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. These criteria included: CTCAE Grade greater than or equal to (≥) 3 non-hematological toxicity, with exceptions for nausea, vomiting, or constipation, and asymptomatic electrolyte disturbances that can be controlled with standard treatment; Grade 4 hematological toxicity of greater than (\>) 5 days duration; Grade ≥ 3 anemia requiring transfusion; any febrile neutropenia; neutropenia needing granulocyte-colony stimulating factors (GCSFs); Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion; Grade 4 thrombocytopenia.
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria: CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of the patient from the study during Cycle 1).
A DLT was an Adverse Event(AE) observed during the first 28 day cycle that is determined by the investigator to be at least possibly related to LY3039478 according to CTCAE v 4.0 and fulfills any of the following criteria:CTCAE Grade 3 nonhematological toxicity with a few exceptions, any other significant toxicity deemed to be dose limiting.A dose-limiting equivalent toxicity (DLET) was defined as an AE occurring between Day 1 and Day 28 of any cycle (other than Cycle 1) for a patient enrolled in the Phase 1 portion or in any cycle (including Cycle 1) for a patient enrolled in the Phase 2 portion that would have met the criteria for DLT if it had occurred during Cycle 1 for a patient enrolled in the Phase 1 portion.
ORR is defined as the number of participants who achieved a best overall response of either complete remission (CR) or incomplete remission (CRi). The ORR (CR and CRi) is the sum of patients achieving a CR or a CRi divided by the total number of patients randomized in that arm. CR is defined as the number of participants who achieved a best overall response of complete remission (CR), out of the total number of participants randomized in that arm.
DLT was defined as an adverse event (AE) during Cycle 1 (Up to 28 Days) that was related to LY3039478 and fulfilled any 1 of the following criterion using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0): CTCAE Grade 3 non-hematological toxicity with a few exceptions, CTCAE Grade 4 hematological toxicity of greater than 5 days duration, any febrile neutropenia,Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting (for example, any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Parts F1 and F2 compared loading dose three time per week with prednisone versus two times per week with prednisone. Even though the trial may have found an MTD, it did not identify an Recommended Phase 2 dose (RP2D).
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is greater than or equal to (\>=) 30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.
| Arm | Type | Description |
|---|---|---|
| 25 mg LY3039478 | EXPERIMENTAL | Participants received 25 milligrams (mg) of LY3039478, administered orally three times per week (TIW) in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| 50 mg LY3039478 | EXPERIMENTAL | Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met. |
| LY3039478 + Dexamethasone (Adult) | EXPERIMENTAL | Part A: 50 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 75 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 100 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. 125 mg LY3039478 administered orally three times per week (TIW) and 24 mg dexamethasone administered orally on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. |
| LY3039478 + Dexamethasone (Pediatric) | EXPERIMENTAL | Part B: LY3039478 administered orally TIW at escalating doses and dexamethasone administered orally twice a day (BID) on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Part B of the study. |
| Phase 2: LY3039478 + Dexamethasone | EXPERIMENTAL | LY3039478 administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study. |
| Phase 2: Placebo + Dexamethasone | PLACEBO_COMPARATOR | Placebo administered orally TIW and dexamethasone administered orally BID on days 1-5 every other week during 28 day cycles. Participants receiving benefit may continue until disease progression. There were no participants enrolled to Phase 2 of the study. |
| LY3039478 - Dose Escalation | EXPERIMENTAL | 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 |
| LY3039478 - Cohort Expansion | EXPERIMENTAL | 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. |
| Dose 1 LY3039478 + Prednisone | EXPERIMENTAL | 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. |
| Dose 2 LY3039478 + Prednisone | EXPERIMENTAL | 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. |
| Name | Type | Description |
|---|---|---|
| LY3039478 | DRUG | Administered orally |
| Dexamethasone | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Prednisone | DRUG | Administered orally |
Inclusion Criteria: * Histological or cytological evidence of a diagnosis of solid tumor that is advanced and/or metastatic. * In the judgment of the investigator, participants must be appropriate candidates for experimental therapy after available standard therapies have failed or for whom standar...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 2 | PHASE2 | pembrolizumab |
| Incyte Corporation | INCY | 1 | PHASE2 | Chemotherapy, Retifanlimab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | E7 TCR-T cells, Aldesleukin |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115, pembrolizumab |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
LY3039478 is an investigational small molecule being studied for use in oncology. It has been evaluated in clinical trials for advanced solid tumors, neoplasms, lymphoma, and T-cell acute lymphoblastic leukemia. The drug is in Phase 1 clinical development and is not yet approved by regulatory authorities.
LY3039478 is being developed by Eli Lilly and Company, a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol LLY. The drug is currently in Phase 1 clinical trials and remains investigational.
LY3039478 is in Phase 1 clinical development. All three clinical trials for the drug have been completed. It is an investigational agent and has not received regulatory approval for any indication.
LY3039478 has been studied in three completed Phase 1 trials. NCT01695005 evaluated the drug in 247 participants with advanced cancer. NCT02659865 and NCT02906618 studied it in healthy participants, and NCT02917733 examined its absorption, distribution, metabolism, and excretion in healthy participants.
LY3039478 is the primary identifier for this investigational compound. No alternative names for the drug have been disclosed in the clinical trial records. It is a small molecule being developed by Eli Lilly and Company for oncology indications.