Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Galunisertib · 8 trials · 12 indications
Percentage of participants with hematological improvement (HI) based on International Working Group (IWG) 2006 criteria in participants with very low, low, and intermediate-risk myelodysplastic syndromes treated with Galunisertib plus best supportive care, as assessed by the International Prognostic Scoring System (IPSS-R). To be classified as an HI responder, the HI response must have lasted at least 8 weeks (56 days).
Comparison of the percentage of participants with very low-, low-,and intermediate-risk MDS who were transfusion-free or had an increase ≥1.5 g/dL in hemoglobin (Hb) maintained for at least 8 weeks within the first 24 weeks of treatment with galunisertib plus best supportive care or placebo plus best supportive care and assessed by IPSS-R. The Phase 3 portion of this study was not conducted because efficacy level required in phase 2 to move forward to phase 3 was not achieved.
OS is defined as the time from the date of randomization until death from any cause. For participants not known to have died by the data-inclusion cutoff date, OS is censored at the last date they were known to be alive.
Completion of 4 cycles of CT + GB- completion of a cycle will be defined as receiving both carboplatin/paclitaxel and taking ≥75% of the doses of GB for the cycle.
The MTD is defined as the highest tested dose that has less than 33% probability of causing a dose limiting toxicity (DLT).
The recommended Phase 2 dose was the highest dose where less than 1/3 of participants experienced dose limiting toxicities (DLTs). The recommended dose was determined based on a review of overall toxicity, dose reductions, omissions, and pharmacokinetic information from Phase 1b.
Overall survival is defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
| Arm | Type | Description |
|---|---|---|
| Phase (ph) 2: Galunisertib + BSC | EXPERIMENTAL | Ph 2. 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. |
| Ph 3: Placebo + BSC | PLACEBO_COMPARATOR | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive BSC according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm. |
| Ph 3: Galunisertib + BSC | EXPERIMENTAL | 150 milligrams Galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Participants will receive best supportive care (BSC) according to institutional guidelines. Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. This arm is contingent on the data from the phase 2 arm. |
| Arm A: Galunisertib | EXPERIMENTAL | * Participants received Galunisertib 300 milligrams (mg) orally twice daily (BID) for 14 days, followed by 14 days of rest in a 28-day cycle. * Treatment continued until disease progression, death, or discontinuation criteria were met. |
| Arm B: Galunisertib + Lomustine | EXPERIMENTAL | * Participants received Galunisertib 300 mg orally BID for 14 days, followed by 14 days of rest in a 28-day cycle. * Participants received a first dose of Lomustine at 100 milligrams per square meter (mg/m²) administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator. * Treatment continued until disease progression, death, or discontinuation criteria were met. |
| Arm C: Lomustine + Placebo | ACTIVE_COMPARATOR | * Participants received a first dose of Lomustine at 100 mg/m² administered orally. Thereafter, starting with the second dose, Lomustine was administered orally once every 6 weeks at 100-130 mg/m², at the discretion of the investigator. * Participants received Galunisertib-matched Placebo orally BID for 14 days, followed by 14 days of rest in a 28-day cycle. * Treatment continued until disease progression, death, or discontinuation criteria were met. |
| Paclitaxel/Carboplatin + Galunisertib | EXPERIMENTAL | Patients will receive the following in every cycle (1 cycle=28days). * Paclitaxel - 175 mg/m2 over 3 hours via IV on Day 1 * Carboplatin - AUC 6\* (or AUC 5\*) over 1 hour via IV on Day 1 * Galunisertib - 150mg orally twice a day on Days 4-17 |
| Galunisertib + Durvalumab | EXPERIMENTAL | (Dose Escalation and Cohort Expansion) Galunisertib administered orally in combination with durvalumab administered intravenously (IV). |
| Part A Galunisertib - 1 tablet | EXPERIMENTAL | Single oral dose of galunisertib in Japanese participants |
| Part A Galunisertib - 2 tablets | EXPERIMENTAL | Single oral dose of galunisertib in Japanese participants |
| Part B Galunisertib - 1 tablet | EXPERIMENTAL | Single oral dose of galunisertib in non-Japanese participants |
| Part B Galunisertib - 2 tablets | EXPERIMENTAL | Single oral dose of galunisertib in non-Japanese participants |
| Galunisertib | EXPERIMENTAL | 150 milligrams galunisertib given orally twice daily (BID) for 14 days followed by 14 days with no study drug (28 day cycles). Treatment is expected to last for 6 cycles. Participants may receive additional cycles if they are deriving clinical benefit. |
| Galunisertib + Nivolumab (Cohort 1) Phase 1b | EXPERIMENTAL | 50 milligrams (mg) Galunisertib administered orally once daily (QD) on Day 1 through Day 14 of each 4-week cycle in combination with 3 milligrams per kilogram (3 mg/kg) nivolumab given intravenously (IV), every 2 weeks (Q2W), (Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met. |
| Galunisertib + Nivolumab (Cohort 2) Phase 1b | EXPERIMENTAL | 50 mg Galunisertib administered orally twice daily (BID) on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W,(Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met. |
| Galunisertib + Nivolumab (Cohort 3) Phase 1b | EXPERIMENTAL | 80 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met. |
| Galunisertib + Nivolumab (Cohort 4) Phase 1b | EXPERIMENTAL | 150 mg Galunisertib administered orally BID on Day 1 through Day 14 of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W,(Day 1 and Day 15). Participants may continue to receive study drug until discontinuation criteria are met. |
| Galunisertib + Nivolumab - Non-small Cell Lung Cancer (NSCLC) Phase 2 | EXPERIMENTAL | 150 mg Galunisertib administered orally BID for the first 14 days of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met. |
| Galunisertib + Nivolumab - Hepatocellular Carcinoma (HCC) Phase 2 | EXPERIMENTAL | 150 mg Galunisertib administered orally BID for the first 14 days of each 4-week cycle in combination with 3 mg/kg nivolumab given IV, Q2W, (Day 1 and Day 15) of each 4-week cycle. Participants may continue to receive study drug until discontinuation criteria are met. |
| Phase 1b: 80 mg Galunisertib + Gemcitabine | EXPERIMENTAL | Cohort 1: 40 mg Galunisertib was administered orally twice daily (BID) for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks. |
| Phase 1b: 160 mg Galunisertib + Gemcitabine | EXPERIMENTAL | Cohort 2: 80 mg Galunisertib was administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks. |
| Phase 1b: 300 mg Galunisertib + Gemcitabine | EXPERIMENTAL | Cohort 3: 150 mg Galunisertib was administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks. |
| Phase 2: Recommended dose of Galunisertib + Gemcitabine | EXPERIMENTAL | Galunisertib recommended dose (300 mg) determined from phase 1, administered orally twice daily for 14 days followed by 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks. |
| Phase 2: Placebo + Gemcitabine | EXPERIMENTAL | Placebo administered orally twice daily for 14 days followed 14 days of rest (28 day cycle). Gemcitabine at a dose of 1000 mg/m\^2 was administered intravenously once per week for 7 weeks followed by 1 week of rest and then once per week for 3 weeks of every 4 weeks. |
| Name | Type | Description |
|---|---|---|
| Galunisertib | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Lomustine | DRUG | Administered orally |
| Paclitaxel | DRUG | IV Day 1: Paclitaxel 175 mg/m2 over 3 hours |
| Carboplatin | DRUG | IV Day 1: Carboplatin AUC 6\* over 1 hour (or 5\* if prior radiation therapy) |
| Durvalumab | DRUG | Administered IV |
| Nivolumab | DRUG | Administered IV |
| Gemcitabine | DRUG | Administered intravenously |
Inclusion Criteria: * Confirmed diagnosis of MDS based on the World Health Organization (WHO) criteria * Participants with 5q deletions are allowed only if they have failed or are intolerant of lenalidomide treatment * Participants must have a Revised International Prognostic Scoring System (IPSS-R...
Galunisertib is an investigational small molecule being studied for use in oncology, including myelodysplastic syndromes, neoplasms, glioblastoma, carcinosarcoma, ovarian cancer, and solid tumors. It is developed by Eli Lilly and Company and is currently in clinical trials, though it is not yet approved by the FDA.
Galunisertib is a small molecule that targets the TGF-beta receptor, inhibiting its activity. By blocking this pathway, it aims to disrupt tumor growth and progression. This mechanism is being explored in various cancer types, including glioblastoma and solid tumors, as part of Eli Lilly's oncology pipeline.
Galunisertib is developed by Eli Lilly and Company, a pharmaceutical company traded on the NYSE under the ticker LLY. The drug is currently in clinical development for multiple oncology indications, including glioblastoma and solid tumors, though it has not yet received regulatory approval.
Galunisertib is in Phase 1 clinical development, with one completed Phase 1 trial. It has also been studied in a Phase 2 trial for recurrent glioblastoma, which is completed. The drug remains investigational and is not yet approved by the FDA for any indication.
Galunisertib has been studied in several completed trials, including NCT01373164 for metastatic cancer and pancreatic cancer, NCT01582269 for recurrent glioblastoma, NCT02752919 in healthy participants, and NCT03206177 for carcinosarcoma of the uterus or ovary. These trials have collectively enrolled over 390 participants.
Galunisertib is also known as LY2157299, an alternative name used in clinical research. It is a small molecule TGF-beta receptor inhibitor developed by Eli Lilly and Company. The drug is being investigated for various cancers, including glioblastoma and solid tumors, but is not yet approved.