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Also known as [^14C]-LY2157299
LY2157299 · 10 trials · 8 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.
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.
| 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. |
| 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. |
| 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 (Fasted) | EXPERIMENTAL | Single dose of 150 mg LY2157299 administered orally in fasted state in one of two study periods. |
| LY2157299 (Fed) | EXPERIMENTAL | Single dose of 150 mg LY2157299 administered orally in fed state in one of two study periods. |
| [^14C]-LY2157299 | EXPERIMENTAL | Single 150 mg oral dose of LY2157299 monohydrate containing 100 micro curies of \[\^14C\] labeled drug |
| 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 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 |
| Ramucirumab | DRUG | Administered IV |
| Gemcitabine | DRUG | Administered IV |
| [^14C]-LY2157299 | DRUG | \[\^14C\]-LY2157299 monohydrate administered as oral solution |
| Radiation | DRUG | Administered as approved |
| Temozolomide | DRUG | Administered orally |
| Lomustine | 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...
LY2157299 is an investigational small molecule developed by Eli Lilly and Company for oncology indications. It has been studied in glioma, hepatocellular carcinoma, pancreatic neoplasms, rectal adenocarcinoma, other neoplasms, and in healthy volunteers. It is not an approved therapy and remains in clinical development.
LY2157299 has been studied in hepatocellular carcinoma, including advanced and unresectable disease. Trials in this indication enrolled participants in Japan, China, Hong Kong, South Korea, Taiwan, and Thailand. It is investigational and has not been approved for the treatment of hepatocellular carcinoma or any other condition.
LY2157299 is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly is the sponsor of the clinical trials evaluating the compound across several tumor types, including hepatocellular carcinoma, rectal adenocarcinoma, and pancreatic neoplasms.
LY2157299 is in clinical development, with trials conducted across Phase 1 and Phase 2. It is an investigational agent and is not FDA approved. The program includes completed Phase 1 and Phase 2 studies and one active Phase 2 study that is no longer recruiting participants.
Registered trials include NCT02688712, an active Phase 2 study in rectal adenocarcinoma; NCT02240433, a completed Phase 1 study in unresectable hepatocellular carcinoma in Japan; NCT02178358, a completed Phase 2 study in advanced hepatocellular carcinoma in Asia; and NCT02154646, a completed Phase 1 study in advanced pancreatic cancer in Japan.
Yes. [^14C]-LY2157299 is an alternative designation for LY2157299, referring to a carbon-14 labeled form of the compound used in research. Searches for either name refer to the same Eli Lilly investigational small molecule being studied in oncology indications.