Trial Outcomes & Findings for Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors (NCT NCT01199822)

NCT ID: NCT01199822

Last Updated: 2017-04-14

Results Overview

Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 16 participants
• Primary outcome timeframe: First dose to study completion up to 5.6 months
• Results posted on: 2017-04-14

Participant Flow

There were 3 cohorts and enrollment into the next cohort did not occur until all participants in the previous cohort completed 1 cycle of treatment or discontinued due to dose-limiting toxicity (DLT). Participants who completed Cycle 1 or had DLT during Cycle 1 are considered having completed study.

Participant milestones

Measure	10 mg/kg Olaratumab (IMC-3G3) 10 milligrams/kilogram (mg/kg) olaratumab intravenously (IV) administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of progressive disease (PD), or until other withdrawal criteria were met.	20 mg/kg Olaratumab 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Overall Study STARTED	3	7	6
Overall Study Received at Least 1 Dose of Study Drug	3	7	6
Overall Study COMPLETED	3	6	6
Overall Study NOT COMPLETED	0	1	0

Reasons for withdrawal

Measure	10 mg/kg Olaratumab (IMC-3G3) 10 milligrams/kilogram (mg/kg) olaratumab intravenously (IV) administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of progressive disease (PD), or until other withdrawal criteria were met.	20 mg/kg Olaratumab 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Overall Study Investigator discontinued therapy	0	1	0

Baseline Characteristics

Study of the Safety and Pharmacokinetics of Olaratumab (IMC-3G3) in Japanese Participants With Solid Tumors

Baseline characteristics by cohort

Measure	10 mg/kg Olaratumab n=3 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	Total n=16 Participants Total of all reporting groups
Age, Customized 20 - <65 Years	1 participants n=5 Participants	6 participants n=7 Participants	4 participants n=5 Participants	11 participants n=4 Participants
Age, Customized ≥65 Years	2 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	5 participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	16 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Japan	3 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	16 participants n=4 Participants

PRIMARY outcome

Timeframe: First dose to study completion up to 5.6 months

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

Data presented are the number of participants who experienced AEs of any grade and AEs of Grade ≥3 as determined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 4.02. A summary of serious adverse events (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Measure	10 mg/kg Olaratumab n=3 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Number of Participants With Adverse Events (AEs) AE of Any Grade	3 participants	7 participants	6 participants
Number of Participants With Adverse Events (AEs) AE of Grade ≥3	1 participants	1 participants	0 participants

PRIMARY outcome

Timeframe: First dose to study completion up to 5.6 months

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

A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Outcome measures

Measure	10 mg/kg Olaratumab n=3 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Number of Participants With SAEs	0 participants	1 participants	0 participants

PRIMARY outcome

Timeframe: First dose through Cycle 1 (6 weeks/cycle)

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

A DLT is defined as 1 of the following events, if considered by the investigator to be definitely, probably, or possibly related to olaratumab: NCI-CTCAE v4.02 Grade 4 neutropenia lasting >7 days; NCI-CTCAE v4.02 Grade ≥3 thrombocytopenia with signs of bleeding or requiring platelet transfusions; NCI-CTCAE v4.02 Grade ≥3 neutropenia associated with fever; NCI-CTCAE v4.02 Grade 3 or 4 nonhematologic toxicity, excluding electrolyte abnormality; NCI-CTCAE v4.02 Grade ≥3 skin toxicity despite best preemptive and supportive care; and/or NCI-CTCAE v4.02 Grade ≥3 diarrhea, nausea, or vomiting despite best preemptive and supportive care.

Outcome measures

Measure	10 mg/kg Olaratumab n=3 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Number of Participants With a Dose- Limiting Toxicity (DLT) in Cycle 1	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Cycle 2: Pre-dose and up to 336 hours post-dose

Population: All participants who received study drug and had pharmacokinetic (PK) data available to calculate Cmax. Due to the limited data, Cmax is not representative of the study population.

Outcome measures

Measure	10 mg/kg Olaratumab n=2 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=3 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=1 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Maximum Concentration (Cmax) of Olaratumab Following Multiple Doses	603 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation NA 2 participants were analyzed; therefore arithmetic mean was calculated and geometric coefficient of variation was not calculated.	1160 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation 91	921 micrograms/milliliter (µg/mL) Geometric Coefficient of Variation NA 1 participant was analyzed; therefore actual value was presented and geometric coefficient of variation was not calculated.

SECONDARY outcome

Timeframe: Cycle 2: Pre-dose and up to 336 hours post-dose

Population: All participants who received study drug and had PK data available to calculate AUCτ. Zero participants were analyzed for groups of 10 mg/kg IMC-3G3 and 15 mg/kg IMC-3G3 because of insufficient amount of samples collected. Due to the limited data, AUCτ is not representative of the study population.

Outcome measures

Measure	10 mg/kg Olaratumab 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=3 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Area Under the Concentration of Olaratumab Versus Time Curve During One Dosing Interval (AUCτ) Following Multiple Doses	—	123000 micrograms*hours/milliliter (µg*h/mL) Geometric Coefficient of Variation 29	—

SECONDARY outcome

Timeframe: Cycle 2: Pre-dose and up to 336 hours post-dose

Population: All participants who received study drug and had PK data available to calculate t1/2. Due to limited data and the relatively short duration of sample collection, t1/2 is not representative of the study population.

t1/2 is the time it takes for the drug concentration in serum to decrease to half the value observed at the beginning of the time period.

Outcome measures

Measure	10 mg/kg Olaratumab n=2 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=3 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=1 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Terminal Elimination Half-Life (t1/2) of Olaratumab	NA days Interval 4.06 to 7.33 2 participants were analyzed; therefore geometric mean was not calculated.	7.33 days Interval 5.42 to 8.83	8.25 days 1 participant was analyzed; therefore actual value was presented and range was not provided.

SECONDARY outcome

Timeframe: Cycle 2: Pre-dose and up to 336 hours post-dose

Population: All participants who received study drug and had PK data available to calculate CLss. Zero participants were analyzed for groups of 10 mg/kg IMC-3G3 and 15 mg/kg IMC-3G3 because of insufficient amount of samples collected. Due to limited data, CLss is not representative of the study population.

CLss is the volume of plasma (or blood) from which the drug is completely removed, or cleared, in a given time at steady-state.

Outcome measures

Measure	10 mg/kg Olaratumab 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=3 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Clearance of Olaratumab at Steady State (CLss)	—	0.163 milliliters/hour/kilogram (mL/h/kg) Geometric Coefficient of Variation 29	—

SECONDARY outcome

Timeframe: Cycle 2: Pre-dose and up to 336 hours post-dose

Population: Zero participants were analyzed because of insufficient amount of samples collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First dose to study completion up to 5.6 months

Population: All participants who received at least one dose of study drug and had evaluable baseline and evaluable post-baseline antibody data.

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

Measure	10 mg/kg Olaratumab n=15 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Number of Participants With Serum Anti-Olaratumab Antibody Assessment (Immunogenicity)	0 participants	—	—

SECONDARY outcome

Timeframe: First dose to study completion up to 5.6 months

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

Data presented are the number of participants who experienced a treatment related AE of any grade.

Outcome measures

Measure	10 mg/kg Olaratumab n=3 Participants 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 Participants 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 Participants 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Number of Participants With Treatment Related AEs Hyperglycaemia	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Any treatment related AE	1 participants	6 participants	1 participants
Number of Participants With Treatment Related AEs Anaemia	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Leukopenia	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Diarrhoea	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Fatigue	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Aspartate aminotransferase increased	0 participants	2 participants	0 participants
Number of Participants With Treatment Related AEs Fibrin D dimer increased	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Tumour haemorrhage	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Proteinuria	0 participants	3 participants	1 participants
Number of Participants With Treatment Related AEs Cough	1 participants	0 participants	0 participants
Number of Participants With Treatment Related AEs Dermatitis	0 participants	0 participants	1 participants
Number of Participants With Treatment Related AEs Rash	0 participants	1 participants	0 participants
Number of Participants With Treatment Related AEs Hypertension	0 participants	1 participants	0 participants

Adverse Events

10 mg/kg Olaratumab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

20 mg/kg Olaratumab

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

15 mg/kg Olaratumab

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	10 mg/kg Olaratumab n=3 participants at risk 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 participants at risk 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 participants at risk 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6

Other adverse events

Measure	10 mg/kg Olaratumab n=3 participants at risk 10 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	20 mg/kg Olaratumab n=7 participants at risk 20 mg/kg olaratumab IV administered on Day 1 every 2 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.	15 mg/kg Olaratumab n=6 participants at risk 15 mg/kg olaratumab IV administered on Days 1 and 8, every 3 weeks (6-week cycle). Cycles repeated until there was evidence of PD, or until other withdrawal criteria were met.
Blood and lymphatic system disorders Anaemia	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6
Blood and lymphatic system disorders Leukopenia	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6
Gastrointestinal disorders Abdominal pain	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6
Gastrointestinal disorders Constipation	0.00% 0/3	28.6% 2/7 • Number of events 2	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Diarrhoea	0.00% 0/3	14.3% 1/7 • Number of events 1	16.7% 1/6 • Number of events 2
Gastrointestinal disorders Nausea	0.00% 0/3	0.00% 0/7	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Periodontal disease	33.3% 1/3 • Number of events 1	0.00% 0/7	0.00% 0/6
General disorders Fatigue	0.00% 0/3	14.3% 1/7 • Number of events 2	16.7% 1/6 • Number of events 2
General disorders Malaise	0.00% 0/3	0.00% 0/7	16.7% 1/6 • Number of events 1
General disorders Pyrexia	0.00% 0/3	57.1% 4/7 • Number of events 5	0.00% 0/6
Investigations Aspartate aminotransferase increased	0.00% 0/3	28.6% 2/7 • Number of events 3	0.00% 0/6
Investigations Fibrin D dimer increased	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6
Investigations Weight decreased	0.00% 0/3	0.00% 0/7	33.3% 2/6 • Number of events 3
Metabolism and nutrition disorders Anorexia	0.00% 0/3	14.3% 1/7 • Number of events 1	33.3% 2/6 • Number of events 4
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6
Musculoskeletal and connective tissue disorders Musculoskeletal pain	33.3% 1/3 • Number of events 1	0.00% 0/7	0.00% 0/6
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/3	0.00% 0/7	33.3% 2/6 • Number of events 4
Nervous system disorders Cognitive disorder	33.3% 1/3 • Number of events 1	0.00% 0/7	0.00% 0/6
Nervous system disorders Headache	0.00% 0/3	0.00% 0/7	16.7% 1/6 • Number of events 1
Psychiatric disorders Insomnia	0.00% 0/3	0.00% 0/7	33.3% 2/6 • Number of events 2
Renal and urinary disorders Proteinuria	0.00% 0/3	42.9% 3/7 • Number of events 3	16.7% 1/6 • Number of events 1
Reproductive system and breast disorders Metrorrhagia	— 0/0	50.0% 1/2 • Number of events 1	0.00% 0/4
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • Number of events 1	0.00% 0/7	16.7% 1/6 • Number of events 1
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/3	0.00% 0/7	16.7% 1/6 • Number of events 1
Skin and subcutaneous tissue disorders Rash	0.00% 0/3	14.3% 1/7 • Number of events 1	16.7% 1/6 • Number of events 1
Vascular disorders Hypertension	0.00% 0/3	14.3% 1/7 • Number of events 1	0.00% 0/6

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
• Publication restrictions are in place

Restriction type: OTHER