Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level in non-target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having at least a 20% increase in the sum of the LD of target lesion and appearance of ≥1 new lesion and/or unequivocal progression of existing nontarget lesions. SD was defined as small changes that did not meet the above criteria taking as reference the smallest sum LD since treatment started.

The effect of LY2228820 on PD biomarker was measured as MAPK-activated protein kinase -2 (MAPKAP-K2) level which is regulated by p38 MAPK activity. Inhibition of p38 MAPK activity will result in lower levels of MAPKAPK-2.

40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle.

160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.

Total of all reporting groups

20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle.

160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.

Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest dose level at which no more than 33% of participants experience a DLT during Cycle 1.

Any participant who received at least 1 dose of study drug.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level in non-target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having at least a 20% increase in the sum of the LD of target lesion and appearance of ≥1 new lesion and/or unequivocal progression of existing nontarget lesions. SD was defined as small changes that did not meet the above criteria taking as reference the smallest sum LD since treatment started.

All participants who received at least 1 dose of study drug.

All participants who received at least 1 dose of study drug and had evaluable PK data. Participants in 300 mg and 420 mg are combined to measure PK outcome; as dose, formulations and population are same.

All participants who received at least 1 dose of study treatment and had evaluable PK data. Participants in 300 mg and 420 mg are combined to measure PK outcome; as dose, formulations and population are same.

The effect of LY2228820 on PD biomarker was measured as MAPK-activated protein kinase -2 (MAPKAP-K2) level which is regulated by p38 MAPK activity. Inhibition of p38 MAPK activity will result in lower levels of MAPKAPK-2.

All participants who received at least 1 dose of study drug and had evaluable PD data. At the dose confirmation of 300 mg, the pMAPKAP-K2 inhibition reached above 50% on Day 1 as maximum inhibition.

20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle.

160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria.

420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met.

200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.

300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.