A Study of Nab-Paclitaxel and Gemcitabine With or Without Olaratumab (LY3012207) in Participants With Metastatic Pancreatic Cancer

A DLT is defined as an adverse event that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE version 4.03: 1. Any febrile neutropenia 2. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by clinically significant hemorrhage 3. Grade 4 neutropenia lasting 7 days or longer 4. Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, diarrhea which can be controlled with optimal medical management within 48 hours; non-clinically significant, treatable, or reversible laboratory abnormalities including liver function tests, uric acid, electrolytes, etc. 5. Any other significant toxicity deemed to be dose-limiting (e.g., any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).

Time frame: Cycle 1 (Up to 28 days)

Population: All participants in phase 1b who received at least one dose of Olaratumab.

OS is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. For any participant who has withdrawn consent for further follow-up of survival data, OS will be censored at the last date for which the participant consented to be followed for the study.

Time frame: Baseline to Date of Death from Any Cause (Up To 29 Months)

Population: All randomized participants in phase 2 (including the censored participants). Number of participants censored in Olaratumab+Nab-paclitaxel+Gemcitabine=26, Placebo+Nab-paclitaxel+Gemcitabine=21.

DoR is defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence.

Time frame: From Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 19 Months)

Population: All participants in phase 1b/2 who had CR or PR responses. For phase 1b cohort expansion arm, there were no participants with CR or PR responses to evaluate DoR, hence, zero participants analysed.

ORR is the best overall tumor response of CR or PR as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Time frame: Baseline through Disease Progression or Death (Up To 26 Months)

Population: All participants in phase 1b/2.

PK: Cmin of olaratumab

Time frame: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 3 Day 1, Cycle 3 Day 15

Population: All participants in phase 1b/2 who received at least one dose of Olaratumab and had evaluable PK data.

OS is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive. For any participant who has withdrawn consent for further follow-up of survival data, OS will be censored at the last date for which the participant consented to be followed for the study.

Time frame: Baseline to Date of Death from Any Cause (Approximately 9 Months)

Population: Phase 1b: Zero participants analysed as data was not collected. OS was not measured in phase 1b.

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.

Time frame: Cycle 1 Day 1, Cycle 7 Day 1

Population: All randomized participants in phase 2 who completed EQ-5D-5L.

Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies

Time frame: Baseline through Follow-up (Up To 29 Months)

Population: All randomized participants in phase 2 who received at least one dose of Olaratumab and had evaluable immunogenicity data.

PFS is defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 \[RECIST v.1.1\]) or death due to any cause in the absence of progressive disease (PD). PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who did not progress or are lost to follow-up were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available. If death or PD occurs after 2 or more consecutive missing radiographic visits, censoring will occur at the date of the last radiographic visit prior to the missed visits.

Time frame: Baseline to Disease Progression or Death (Up To 26 Months)

Population: All randomized participants in phase 2 (including the censored participants). Number of participants censored in Olaratumab+Nab-paclitaxel+Gemcitabine=24, Placebo+Nab-paclitaxel+Gemcitabine=26.

The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems.

Time frame: Baseline through Follow-up (Up To 21 Months)

Population: All randomized participants in phase 2 who had baseline and at least one post-baseline assessment.

The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf worst pain score (TWP) was defined as the time from the date of randomization to the first date of either a worst pain score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the participant has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered.

Time frame: Baseline through Follow-up (Up To 21 Months)

Population: All randomized participants in phase 2 who had baseline and at least one post-baseline assessment.