Trial Outcomes & Findings for A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (NCT NCT00918203)

Last Updated: 2019-01-10

Results Overview

PFS is defined as the time from the day of randomization to the first evidence of progression by RECIST version 1.1, or death from any cause. Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of their last tumor assessment. If there was no radiologic assessment at baseline or post baseline, participants were censored at the date of randomization. If death or progressive disease (PD) occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

Baseline to Measured PD or Death From Any Cause (Up to 31 Months)

Results posted on

2019-01-10

Participant Flow

Participants who had evidence of progressive disease (PD), died or crossover to Olaratumab were considered to have completed the study.

Participant milestones

Participant milestones
Measure	Olaratumab + Paclitaxel + Carboplatin Olaratumab: 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel 200 milligram/square meter (mg/m2) over 3 hrs (Day 1) Carboplatin Area Under Concentration (AUC)=6 (Day 1) of each 21-day cycle Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants who experience progressive disease may cross over to olaratumab monotherapy. Paclitaxel: 200 mg/m2 is then administered intravenously (IV) over 3 hours carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Monotherapy Olaratumab was administered IV at 15 mg/kg on Day 1 and Day 8 every 3 weeks.
Treatment With or Without Olaratumab STARTED	70	67	0
Treatment With or Without Olaratumab Received at Least 1 Dose of Study Drug	67	64	0
Treatment With or Without Olaratumab Death Due to Any Cause	53	47	0
Treatment With or Without Olaratumab Alive/On Study at End/Off Treatment	11	10	0
Treatment With or Without Olaratumab COMPLETED	64	57	0
Treatment With or Without Olaratumab NOT COMPLETED	6	10	0
Crossover to Olaratumab Monotherapy STARTED	0	0	18
Crossover to Olaratumab Monotherapy COMPLETED	0	0	18
Crossover to Olaratumab Monotherapy NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Olaratumab + Paclitaxel + Carboplatin Olaratumab: 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel 200 milligram/square meter (mg/m2) over 3 hrs (Day 1) Carboplatin Area Under Concentration (AUC)=6 (Day 1) of each 21-day cycle Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants who experience progressive disease may cross over to olaratumab monotherapy. Paclitaxel: 200 mg/m2 is then administered intravenously (IV) over 3 hours carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.
Treatment With or Without Olaratumab Lost to Follow-up	1	1
Treatment With or Without Olaratumab Withdrawal by Subject	2	8
Treatment With or Without Olaratumab Other Therapy Started	2	1
Treatment With or Without Olaratumab Never Treated/Death	1	0

Baseline Characteristics

A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab 15 mg/kg over 30 mins (Days 1 and 8) plus Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants can remain on study after completing chemotherapy and receive olaratumab monotherapy on Days 1 and 8, provided there is ongoing evidence of clinical benefit. Olaratumab: 15 mg/kg of olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Total n=131 Participants Total of all reporting groups
Age, Continuous	63.6 years STANDARD_DEVIATION 10.77 • n=5 Participants	63.8 years STANDARD_DEVIATION 9.67 • n=7 Participants	63.7 years STANDARD_DEVIATION 10.21 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	30 Participants n=7 Participants	57 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	34 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	64 Participants n=5 Participants	62 Participants n=7 Participants	126 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	6 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) White	54 Participants n=5 Participants	56 Participants n=7 Participants	110 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG PS 0	25 participants n=5 Participants	16 participants n=7 Participants	41 participants n=5 Participants
Eastern Cooperative Oncology Group Performance Status (ECOG PS) ECOG PS 1	42 participants n=5 Participants	48 participants n=7 Participants	90 participants n=5 Participants
Stratification Factor Case Report Form (CRF) Non-Squamous Cell Carcinoma	48 participants n=5 Participants	48 participants n=7 Participants	96 participants n=5 Participants
Stratification Factor Case Report Form (CRF) Squamous Cell Carcinoma	19 participants n=5 Participants	16 participants n=7 Participants	35 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Measured PD or Death From Any Cause (Up to 31 Months)

Population: All randomized participants who received any dose of study drug. Participants censored: paclitaxel + carboplatin = 13, olaratumab + paclitaxel + carboplatin = 20, and crossover to olaratumab = 4. 1 participant did not cross over to Olaratumab until after efficacy data completion, no efficacy data collected on this participant.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab n=17 Participants Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Progression-Free Survival (PFS)	19.1 weeks Interval 16.4 to 23.6	19.0 weeks Interval 15.3 to 25.0	8.3 weeks Interval 5.0 to 13.4

SECONDARY outcome

Timeframe: Baseline to Study Completion (Up to 43 Months)

Population: All randomized participants who received any dose of study drug. 1 participant did not cross over to Olaratumab until after efficacy data completion, no efficacy data collected on this participant.

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab n=17 Participants Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	66 participants	63 participants	10 participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE's	30 participants	21 participants	2 participants

SECONDARY outcome

Timeframe: Up to 43 Months

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab n=17 Participants Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Safety and Tolerability of Olaratumab Administered at a More Rapid Rate (25mg/Min With Minimum Infusion Time of 30 Minutes), Determined by Number of Participants With Treatment Related Adverse Events SAE's	30 participants	21 participants	2 participants
Safety and Tolerability of Olaratumab Administered at a More Rapid Rate (25mg/Min With Minimum Infusion Time of 30 Minutes), Determined by Number of Participants With Treatment Related Adverse Events AE	66 participants	63 participants	10 participants

SECONDARY outcome

Timeframe: Baseline to Death From Any Cause (Up to 31 Months)

Population: All randomized participants who received any dose of study drug. OS data was not analyzed in the crossover olaratumab arm. Participants censored: olaratumab + paclitaxel + carboplatin = 19 and paclitaxel + carboplatin = 20.

Overall survival is defined as the time from date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS was censored on the last date the participants is known to be alive.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Overall Survival (OS)	51.3 weeks Interval 39.7 to 68.7	50.1 weeks Interval 41.4 to 75.9	—

SECONDARY outcome

Timeframe: Baseline to Measured PD or Study Discontinuation (Up to 31 Months)

The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)\*100.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=67 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab n=17 Participants Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)	41.8 percentage of participants Interval 29.8 to 54.5	34.4 percentage of participants Interval 22.9 to 47.3	0 percentage of participants Interval 0.0 to 19.5

SECONDARY outcome

Timeframe: First Criteria Met for CR or PR to Measured PD Start of Other Antitumor Therapy or Death From Any Cause (Up to 31 Months)

Population: All randomized participants who received any dose of study drug and had achieved tumor response of CR or PR. Median Duration of Response data was not analyzed in the crossover olaratumab arm.

The duration of overall response is measured from the time measurement criteria are first met for Complete Response (CR)/Partial Response (PR) (whichever is first recorded) until the first date that the criteria for PD are met (taking as a reference for PD the smallest measurement recorded since the treatment started), initiation of other/additional antitumor therapy is first reported, or death, is objectively documented.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=28 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=22 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Median Duration of Response	14.4 weeks Interval 12.7 to 18.1	12.9 weeks Interval 11.4 to 35.0	—

SECONDARY outcome

Timeframe: Cycle 1: Days 1, 8, and 15 pre- and post-infusion of Olaratumab; Cycles 2-6: day 1 only, pre- and post-infusion of Olaratumab

Population: No data was available due to the collection of plasma samples was not fit for the assessment of PDGFs, as the collection procedure did not prevent platelet activation resulting in elevated levels of PDGFs in the circulation. Pharmacodynamics data was not analyzed in the paclitaxel + carboplatin arm or the crossover to olaratumab arm.

Pharmacodynamics of Olaratumab was determined by analysis of pharmacodynamic markers vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Study Completion (Up to 8 Months)

Population: All randomized participants who had baseline and post baseline Anti-Olaratumab antibodies. Those participants who did not meet eligibility criteria were not included in this assessment.

Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=45 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=4 Participants Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Percentage of Participants With Anti-Olaratumab Antibodies	4.4 percentage of participants	0.0 percentage of participants	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: Predose, 30 minutes (min), 1.5 hours (hrs), 24,48,96,168 Hrs Post Dose

Population: All randomized participants who received any dose of study drug and had evaluable PK data in Cycle 3. PK data was not analyzed in the paclitaxel + carboplatin arm or the crossover to olaratumab arm.

AUC(0-168) = area under the concentration versus time curve from time zero to 168 hours post dose.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=6 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Pharmacokinetics (PK) - Area Under the Curve (AUC) 0-168 of Olaratumab	47600 microgramhour/milliliter (ughr/mL) Geometric Coefficient of Variation 29.2	—	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

Population: All randomized participants who received any dose of study drug and had evaluable PK data in Cycle 3 first dose. PK data was not analyzed in the paclitaxel + carboplatin arm or the crossover to olaratumab arm.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=6 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
PK - Maximum Concentration (Cmax) of Olaratumab	489 micrograms/milliliter (ug/mL) Geometric Coefficient of Variation 13	—	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=6 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
PK - Half-Life (t1/2) of Olaratumab	5.79 days Interval 4.29 to 8.78	—	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hr, 24,48,96,168 Hrs Post Dose

Population: All randomized participants who received any dose of study drug and had evaluable PK data in Cycle 3 first dose.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=6 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
PK - Clearance (Cl) of Olaratumab	0.0218 Liter/hour (L/h) Geometric Coefficient of Variation 24.8	—	—

SECONDARY outcome

Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

Population: All randomized participants who received any dose of study drug and had evaluable PK data in Cycle 3 first dose.

Outcome measures

Outcome measures
Measure	Olaratumab + Paclitaxel + Carboplatin n=6 Participants Olaratumab: 15 mg/kg of Olaratumab on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
PK - Steady State Volume of Distribution (Vss) of Olaratumab	4.22 Liter (L) Geometric Coefficient of Variation 9.51	—	—

Adverse Events

Olaratumab + Paclitaxel + Carboplatin

Serious events: 30 serious events

Other events: 67 other events

Deaths: 0 deaths

Paclitaxel + Carboplatin

Serious events: 21 serious events

Other events: 64 other events

Deaths: 0 deaths

Crossover to Olaratumab

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Olaratumab + Paclitaxel + Carboplatin n=67 participants at risk Olaratumab 15 mg/kg over 30 mins (Days 1 and 8) plus Paclitaxel 200 mg/m2 over 3 hrs (Day 1) Carboplatin AUC=6 (Day 1) of each 21-day cycle Participants can remain on study after completing chemotherapy and receive olaratumab monotherapy on Days 1 and 8, provided there is ongoing evidence of clinical benefit. Olaratumab: 15 mg/kg of IMC-3G3 on Days 1 and 8 of each 21-day cycle, administered IV at 25mg/min, with a minimum infusion time of 30 minutes. Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Paclitaxel + Carboplatin n=64 participants at risk Paclitaxel: 200 mg/m2 is then administered IV over 3 hours Carboplatin: AUC=6 administered IV over 30 minutes on Day 1 of each 3-week cycle for a maximum of six cycles. Once the maximum of 6 cycles of carboplatin are reached the participant may continue on olaratumab maintenance for up to 12 months.	Crossover to Olaratumab n=18 participants at risk Olaratumab monotherapy administered on Days 1 and 8 of each 21-day cycle.
Blood and lymphatic system disorders Anaemia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	3.1% 2/64 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	6.0% 4/67 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Cardiac disorders Atrial flutter	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Cardiac disorders Sinus tachycardia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Duodenal ulcer	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	4.5% 3/67 • Number of events 3 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
General disorders Fatigue	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
General disorders Influenza like illness	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
General disorders Infusion related reaction	0.00% 0/67 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 All randomized participants who received at least one dose of study drug.
General disorders Non-cardiac chest pain	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
General disorders Pyrexia	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Immune system disorders Anaphylactic reaction	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Abscess intestinal	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Cellulitis	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Device related infection	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Diverticulitis	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Eye infection	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	6.2% 4/64 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Pneumonia viral	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Sepsis	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	1.5% 1/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Infections and infestations Wound infection	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Hip fracture	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Incorrect drug administration duration	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Radiation pneumonitis	0.00% 0/67 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Subdural haematoma	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypercalcaemia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypophagia	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscular weakness	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/67 All randomized participants who received at least one dose of study drug.	3.1% 2/64 • Number of events 2 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Nervous system disorders Neuropathy peripheral	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Nervous system disorders Peroneal nerve palsy	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Psychiatric disorders Mental status changes	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Renal and urinary disorders Renal failure acute	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Bronchopleural fistula	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.5% 3/67 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.00% 0/64 All randomized participants who received at least one dose of study drug.	5.6% 1/18 • Number of events 1 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.0% 2/67 • Number of events 2 All randomized participants who received at least one dose of study drug.	6.2% 4/64 • Number of events 4 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/67 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	1.5% 1/67 • Number of events 1 All randomized participants who received at least one dose of study drug.	1.6% 1/64 • Number of events 1 All randomized participants who received at least one dose of study drug.	0.00% 0/18 All randomized participants who received at least one dose of study drug.