Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY2157299, LY2157299 monohydrate
Galunisertib · 15 trials · 16 indications
Complete response is defined as no viable tumor cells identified.
OS defined as the time from the date of randomization to the date of death due to any cause. An overall survival event was defined as death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The number of participants with overall survival events (deaths) is reported.
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.
Biomarker response was defined as a \> 20% decrease in the biomarker AFP from baseline during 8 weeks of treatment. Data presented is median overall survival of those participants who achieved the defined biomarker response. Participants enrolled in Part A had a baseline AFP level of \>1.5 upper limit normal (ULN). Participants enrolled in Part B had baseline AFP level \<1.5 ULN.
Biomarker response was defined as a \> 20% decrease in the biomarker TGF-B from baseline. Data presented is median overall survival of those participants who achieved biomarker response.
TTP is measured from the date of first dose to the first date of progression of disease based on the investigator review of tumor response using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.
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 |
|---|---|---|
| LY2157299 + Chemoradiation + Surgery | EXPERIMENTAL | Patients will receive a 14 day course of LY2157299. On day 15 patients will begin chemoradiation treatment with Capecitabine or Fluorouracil. On day 29, patients will undergo another fourteen day course of LY2157299 concurrent with their ongoing chemoradiation treatment. Six to ten weeks after completing their neoadjuvant therapy, patient will undergo a tumor specific mesorectal excision as per standard of care. |
| 150 milligram (mg) Galunisertib Monotherapy | EXPERIMENTAL | 150 mg galunisertib administered orally, twice daily (BID) for 14 days followed by 14 days with no study drug (28 days cycle). |
| 150 mg Galunisertib + 400 mg Sorafenib Therapy | EXPERIMENTAL | 150 mg galunisertib administered orally, BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| 400 mg Sorafenib + Placebo Therapy | PLACEBO_COMPARATOR | Placebo administered orally BID for 14 days followed by 14 days with no study drug (28 days cycle). 400 mg sorafenib administered orally BID for 28 days. |
| 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. |
| Part A Cohort 1-160 milligram (mg) LY2157299 | EXPERIMENTAL | Per the protocol, following an interim analysis, the decision was taken to no longer randomize participants to the 160 mg LY2157299 arm. As of May 25,2012, all newly enrolled participants will receive 300 mg LY2157299. 80 mg LY2157299 given orally twice daily (BID) for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part A Cohort 2 - 300 mg LY2157299 | EXPERIMENTAL | 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part B - 300 mg LY2157299 | EXPERIMENTAL | 150 mg LY2157299 given orally BID for 14 days followed by 14 days off (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part C Cohort 1 - 160 mg LY2157299 + 800 mg Sorafenib | EXPERIMENTAL | 80 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part C Cohort 2 - 300 mg LY2157299 + 800 mg Sorafenib | EXPERIMENTAL | 150 mg LY2157299 given orally BID on Days 1 to 14 in combination with 400 mg Sorafenib BID on days 1 to 28 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part D Cohort 1 - 160 mg LY2157299 + 8 mg/kg Ramucirumab | EXPERIMENTAL | 80 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kilogram (kg) intravenous (IV) on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is met. |
| Part D Cohort 2 - 300 mg LY2157299 + 8 mg/kg Ramucirumab | EXPERIMENTAL | 150 mg LY2157299 given orally BID on days 1 to 14 in combination with ramucirumab 8 mg/kg IV on days 1 and 15 (28-day cycle). Participants will continue to receive until disease progression, unacceptable toxicity, or another withdrawal criterion is 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). |
| 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. |
| LY2157299 + Sorafenib | EXPERIMENTAL | LY2157299 will be administered orally twice daily for 14 days, followed by 14 days with no study drug per 28-day cycle. Sorafenib will be administered orally twice daily for 28 days, in each cycle. |
| LY2157299 + Gemcitabine | EXPERIMENTAL | 150 mg LY2157299 is administered orally twice daily for 14 days followed by 14 days without study drug (28 day cycle.) Gemcitabine 1000 milligram per square meter will be administered intravenously (IV) on Days 8, 15, and 22 in each cycle (28 day cycle). Participants may continue to receive treatment until discontinuation criteria are met. |
| LY2157299 | EXPERIMENTAL | 80 up to 150 milligrams of LY2157299 administered orally, twice daily for 14 days, followed by 14 days with no study drug (2 weeks on/2 weeks off schedule) for at least two 28 day cycles. Participants receiving clinical benefit may continue receiving treatment until discontinuation criterion is 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. |
| Phase 1: 160 mg LY2157299 | EXPERIMENTAL | During Radiation therapy: * Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. * LY2157299: 80 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. * Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: * LY2157299: 80 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. * Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. |
| Phase 1: 300 mg LY2157299 | EXPERIMENTAL | During Radiation therapy: * Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. * LY2157299: 150 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. * Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: * LY2157299: 150 mg taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. * Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. |
| Phase 2: Established dose LY2157299 | EXPERIMENTAL | During Radiation therapy: * Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. * LY2157299: Phase 1 established dose taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. * Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: * LY2157299: Phase 1 established dose taken twice daily for 14 days on followed 14 days of pause. This on/off schedule constitutes a cycle of 28 days. Taken for a 6 cycles. * Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. |
| Phase 2: no LY2157299 (control) | EXPERIMENTAL | During Radiation therapy: * Radiation:Approximate 1.8 - 2.0 Gy x 30 fractions. Approximate total dose = 60.0 Gy taken 5 days per week for 6 weeks. * Temozolomide: 75 mg/m2 taken daily for 6 weeks. After Radiation Therapy: Temozolomide: 150 mg/m2 and then 200 mg/m2 daily during the off time of LY2157299. Starting 28 days after the completion of radiation therapy. Taken for 5 days followed by 23 days of rest for 6 cycles. |
| LY2157299 (Part A) | EXPERIMENTAL | Administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part A dose escalation will have starting dose of 40 mg/day and may increase up to 360 mg/day. |
| LY2157299 + Lomustine (Part B) | EXPERIMENTAL | LY21547299 will be administered orally by tablet twice daily for two weeks followed by two weeks of no treatment for two 28-day cycles. Part B dose expansion will have starting dose of 80 mg twice daily and may increase up to 150 mg twice daily. Lomustine will be administered orally by capsule once on Day 7 of Cycle 1 after receiving LY2157299, and once after receiving LY2157299 on Day 21 of Cycles 2, 5, 8, 11, and every 4th cycle thereafter. |
| Name | Type | Description |
|---|---|---|
| LY2157299 | DRUG | Small molecule inhibitor of transforming growth factor-beta signaling pathway |
| Capecitabine | DRUG | Antimetabolite chemotherapy |
| Fluorouracil | DRUG | Antimetabolite chemotherapy |
| Tumor specific mesorectal excision | PROCEDURE | Tumor specific mesorectal excision |
| Sorafenib | DRUG | Administered orally |
| Placebo | DRUG | Administered orally |
| Galunisertib | DRUG | Administered orally |
| Lomustine | DRUG | Administered orally |
| Ramucirumab | DRUG | Administered IV |
| 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 IV |
| Radiation | DRUG | Administered as approved |
| Temozolomide | DRUG | Administered orally |
Inclusion Criteria: * Patients (male and female) with histologically confirmed rectal adenocarcinoma, AJCC Stage IIA-IIIC or AJCC Stage IV appropriate for consideration of primary rectal tumor resection. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Age 18 years or above. * L...
Galunisertib is an investigational small molecule cancer therapy developed by Eli Lilly and Company. It has been studied in Phase 1 clinical trials across several tumor types, including carcinosarcoma of the uterus or ovary, metastatic pancreatic cancer, glioblastoma, myelodysplastic syndromes, and other solid tumors. It is not an approved medicine.
Galunisertib targets TGFBR1, also known as the TGF-beta receptor type 1. It acts as an inhibitor of this receptor. By blocking TGFBR1 signaling, the drug is designed to interfere with a pathway that tumors use to grow and to evade the immune system, which is why it has been tested both alone and with immunotherapy agents.
Galunisertib is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly has sponsored the clinical research program for the drug, including the Phase 1 studies conducted in the United States, Europe, and South Korea.
Galunisertib is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA for any indication. The Phase 1 trials listed for the program are all completed, and no active trials are currently recruiting for this asset.
Galunisertib has been evaluated in completed Phase 1 trials including NCT03206177 in carcinosarcoma of the uterus or ovary with paclitaxel and carboplatin, NCT02734160 in metastatic pancreatic cancer with durvalumab, NCT02423343 in advanced solid tumors with nivolumab, and NCT02304419, which studied its effects on the immune system in cancer patients.
Yes. Galunisertib is the same compound as LY2157299, which is Lilly's internal code name for the molecule. Trial records and publications use both names interchangeably, so searches for LY2157299 refer to the same TGFBR1 inhibitor.