A Study of LY3127804 With Ramucirumab in Participants With Advanced Solid Tumors

Recommended Phase 2 dose was determined based on observed safety, pharmacokinetics (PK) and efficacy. However maximum tolerated dose (MTD) was not determined. For the purpose of this study, the MTD is defined as the highest tested dose in a single-agent setting that has less than (\<) 33% probability of causing a DLT. MTD in the combination setting was determined based on the nature and timing of the DLTs in the combination setting. Dose-limiting toxicities were not reported in any treatment cohort. Therefore, the maximum tolerated LY3127804 dose could not be determined.

Time frame: Baseline through Cycle 1 (28 Day Cycle)

Population: All randomized participants who received at least one dose of study drug (ramucirumab and/or LY3127804) in Part A, Part B and Part C.

The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from cycle 1 pre-Dose through 30 days after last dose of study drug that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Time frame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Up To 5 Months)

Population: All randomized participants who received at least one dose of study drug (ramucirumab and/or LY3127804) and had a baseline and at least 1 post-baseline ADA assessment in Part A, Part B and Part C.

The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from cycle 1 pre-Dose through 30 days after last dose of study drug that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Time frame: Cycle 1 Pre-Dose through 30 Days After Last Dose of Study Drug (Up to 5 Months)

Population: All randomized participants who received at least one dose of study drug (ramucirumab and/or LY3127804) and had a baseline and at least 1 post-baseline ADA assessment in Part A, Part B and Part C.

A dose limiting toxicity (DLT) defined as an adverse event (AE) during the first 21 days that was possibly related to the study drug and fulfilled any of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0: CTCAE Grade 3 nonhematologic toxicity, grade 4 neutropenia that lasted longer than 2 weeks, grade ≥3 thrombocytopenia complicated by hemorrhage, and any hematologic toxicity that caused a cycle delay of \>14 days; a DLT can be declared if a participant experiences increasing toxicity during treatment.

Time frame: Baseline through Cycle 1 (28 Day Cycle)

Population: All randomized participants who received at least one dose of study drug (ramucirumab and/or LY3127804) and had DLTs in Part A, Part B and Part C.

ORR defined as the percentage of participants who achieve a CR or PR as assessed by RECIST v.1.1. The ORR is the number of participants with a complete response (CR) or partial response (PR) divided by the number of randomized participants recorded between the date of randomization and the date of objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first. Complete response (CR) is defined as disappearance of all target (and non-target) lesions, and normalization of tumor marker level. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters of target lesions, taking as reference the baseline sum of longest diameters.

Time frame: Baseline through Measured Progressive Disease or Death (Up to 4 Months)

Population: All randomized participants who had adequate baseline and at least 1 post-baseline tumor assessments in Part A, Part B and Part C.

Area under the serum concentration-time curve of ramucirumab in combination with LY3127804 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (τ) was evaluated following the first dose.

Time frame: predose, end of infusion (1h), 24h, 96h, 168h, 336 h following Ramucirumab dose on day 1

Population: All randomized participants who received at least one dose of study drug (ramucirumab and/or LY3127804) with evaluable PK data in Part B and Part C. Per protocol, Part B reporting arms in cohorts 2 to 6 were combined to measure ramucirumab PK in presence of LY3127804.

Area under the plasma concentration-time curve of LY3127804 over the dosing interval (AUC\[0-τ\]) from time 0 to 336 hours (h) was evaluated.

Time frame: predose, end of infusion (1h), 2h, 24h, 96h, 168h, 336 h following dose on day 1 and at predose, end of infusion (1h), 24h, 168h and 336 h following dose on day 15 and at predose, end of infusion (1h), 2h, 168h, 336h following dose on day 29

Population: All randomized participants who received at least one dose of study drug (LY3127804) with evaluable PK data in Part A, Part B and Part C. Per protocol, similar strength doses of LY3127804 from Part A, B, and C were combined for measuring PK data.

Progression-free survival (PFS) time is defined as the time from the date of randomization to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy.

Time frame: Baseline to Measured Progressive Disease or Death (Up to 4 Months)

Population: All randomized participants who had adequate baseline and at least 1 post-baseline tumor assessments in Part A, Part B and Part C.