NCT02783599

A Study of Olaratumab (LY3012207) in Participants With Soft Tissue Sarcoma

Completed Phase 1 Results posted Last updated 12 August 2019

What this trial tests

Phase 1 trial testing Olaratumab in Soft Tissue Sarcoma in 51 participants. Completed in 5 July 2018.

Timeline

11 October 2016

Primary endpoint
5 July 2018

5 July 2018

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	51
Start date	11 October 2016
Primary completion	5 July 2018
Estimated completion	5 July 2018
Sites	14 locations across France, Italy, United Kingdom, United States, Spain

Drugs / interventions tested

• Olaratumab (OLARATUMAB) — full drug profile →
• Doxorubicin (doxorubicin) — full drug profile →
• External Beam Radiotherapy

Conditions studied

• Soft Tissue Sarcoma — all drugs for Soft Tissue Sarcoma →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Soft Tissue Sarcoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percent Change From Baseline in Enumeration of Circulating Tumor Cells (CTCs) in Whole Blood Primary · Baseline, End of Cycle 1 (21 days)

Enumeration of CTCs pre- and post- treatment with olaratumab may be a useful biomarker given the predilection for sarcomas to spread hematogenously.

Traditional CTCs

Group	Value	95% CI
Olaratumab	846.93	± 3260.60

All Population CTCs

Group	Value	95% CI
Olaratumab	820.11	± 3263.41

Percent Change From Baseline in Gene Expression of Platelet-Derived Growth Factor Receptor Alpha (PGDFRα) and PGDFR Beta (β) in Tumor Tissue Primary · Baseline, End of Cycle 1 (21 days)

Over-activity of PDGF signaling is associated with the development of certain malignant diseases. Olaratumab is an IgG1 antagonist of PDGFRα.

PDGF Receptor α

Group	Value	95% CI
Olaratumab	6162.86	± 32383.49

PDGF Receptor β

Group	Value	95% CI
Olaratumab	1246.25	± 7024.82

Percent Change From Baseline in Gene Expression of PDGF A, PDGF B, PDGF C, and PDGF-D Canonical Ligands in Tumor Tissue Primary · Baseline, End of Cycle 1 (21 days)

PDGF A, PDGF B, PDGF C, and PDGF D are platelet-derived growth factor canonical ligands associated with activation of PDGFR α and β.

Canonical Ligand PDGF - A

Group	Value	95% CI
Olaratumab	189.37	± 672.91

Canonical Ligand PDGF - B

Group	Value	95% CI
Olaratumab	602.01	± 2798.92

Canonical Ligand PDGF - C

Group	Value	95% CI
Olaratumab	1107.45	± 6053.12

Canonical Ligand PDGF - D

Group	Value	95% CI
Olaratumab	2630.36	± 14425.92

Progression Free Survival (PFS) Secondary · Baseline to Objective Progression or Death from Any Cause (Up to 18 Months)

Progression-free survival (PFS) is defined as the time from the date of first study dose to the first date of radiologic disease progression or death due to any cause. Progressive disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or mo

Group	Value	95% CI
Olaratumab + Doxorubicin	2.86	1.41 – 9.72

Objective Response Rate (ORR): Percent of Participants With Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Secondary · Baseline to Measured Progressive Disease (Up to 18 Months)

Overall Response Rate (ORR) is defined as the percentage of participants achieving a best overall response of either Complete Response (CR) or Partial Response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. The best overall response is the best respon

Group	Value	95% CI
Olaratumab + Doxorubicin	11.8

Disease Control Rate (DCR): Percent of Participants Who Exhibit Stable Disease (SD), CR or PR Secondary · Baseline to Measured Progressive Disease (Up to 18 Months)

Disease control rate (DCR) is defined as the percentage of participants achieving a best overall response of CR, PR, or SD as determined by RECIST 1.1. CR is defined as a disappearance of all target lesions and any pathological lymph nodes must have reduction in short axis to \<10 mm and normalization of tumor marker results; PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters; SD is defined as neither sufficient shrinking to qualify as PR nor sufficient increase to qualify for PD. Participants who do not have any p

Group	Value	95% CI
Olaratumab + Doxorubicin	52.9

Percentage of Participants With Resectable Tumors (Resectability Rate) Secondary · Cycle 1 through Cycle 7 (Up to 6 Months)

Resectability rate is obtained when the total number of participants with resectable tumors is divided by the total number of participants. Resectability of a tumor is determined by the surgeon and multi-disciplinary team and dependent on tumor stage and the participants coexisting medical conditions.

Group	Value	95% CI
Olaratumab + Doxorubicin	35.3	22.4306 – 49.9318

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Monotherapy Secondary · Cycle 1 Days 1 and 8: Predose; 5 minutes(m) post-infusion

Summary of Cmax of olaratumab monotherapy on Cycle 1 Day 1 and Day 8

Cycle 1 Day 1

Group	Value	95% CI
Olaratumab	510	± 22

Cycle 1 Day 8

Group	Value	95% CI
Olaratumab	661	± 24

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Olaratumab Secondary · Cycle 2 Day 1: Predose, 5 minutes(m) post-infusion, 24 hours(h), 96h; Day 8:Predose, 5 m, and 24h, 48h, 96h, and 240h postdose; Cycle 3 Day 1 and Day 8: Predose and 5m post-infusion

Cmax of olaratumab Cycles 2 and 3 Day 1 and 8 of a 21-day cycle.

Cycle 2 Day 1

Group	Value	95% CI
Olaratumab + Doxorubicin	624	± 26

Cycle 2 Day 8

Group	Value	95% CI
Olaratumab + Doxorubicin	711	± 28

Cycle 3 Day 1

Group	Value	95% CI
Olaratumab + Doxorubicin	521	± 30

Cycle 3 Day 8

Group	Value	95% CI
Olaratumab + Doxorubicin	601	± 32

Number of Participants With Anti-Olaratumab Antibodies Secondary · Predose Cycle 1 Day 1 through Follow-Up (Up to 8 Months)

A participant is counted as positive if they had at least one anti-olaratumab antibody positive result during the study.

Group	Value	95% CI
Olaratumab + Doxorubicin	1

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline to end of study (Up to 46 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Olaratumab + Doxorubicin

Serious: 22/51 (43%)

Deaths: 3/51

Serious adverse events (21 terms)

Reaction	System	Olaratumab + Doxorubicin
Febrile neutropenia	Blood and lymphatic system disorders	—
Sepsis	Infections and infestations	—
Anaemia	Blood and lymphatic system disorders	—
Atrial fibrillation	Cardiac disorders	—
Cardiopulmonary failure	Cardiac disorders	—
Diarrhoea	Gastrointestinal disorders	—
Gastrointestinal obstruction	Gastrointestinal disorders	—
Intestinal perforation	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Pyrexia	General disorders	—
Anaphylactic reaction	Immune system disorders	—
Anal abscess	Infections and infestations	—
Bronchitis	Infections and infestations	—
Device related infection	Infections and infestations	—
Influenza	Infections and infestations	—
Platelet count decreased	Investigations	—
Joint effusion	Musculoskeletal and connective tissue disorders	—
Dizziness	Nervous system disorders	—
Encephalopathy	Nervous system disorders	—
Guillain-barre syndrome	Nervous system disorders	—
Deep vein thrombosis	Vascular disorders	—

Other adverse events (42 terms — click to expand)

Reaction	System	Olaratumab + Doxorubicin
Nausea	Gastrointestinal disorders	—
Fatigue	General disorders	—
Stomatitis	Gastrointestinal disorders	—
Constipation	Gastrointestinal disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Asthenia	General disorders	—
Diarrhoea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Anaemia	Blood and lymphatic system disorders	—
Neutrophil count decreased	Investigations	—
Neutropenia	Blood and lymphatic system disorders	—
Pyrexia	General disorders	—
White blood cell count decreased	Investigations	—
Dizziness	Nervous system disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Headache	Nervous system disorders	—
Abdominal pain	Gastrointestinal disorders	—
Oedema peripheral	General disorders	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—
Dyspepsia	Gastrointestinal disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Dysgeusia	Nervous system disorders	—
Insomnia	Psychiatric disorders	—
Abdominal pain upper	Gastrointestinal disorders	—
Flatulence	Gastrointestinal disorders	—
Chills	General disorders	—
Procedural pain	Injury, poisoning and procedural complications	—
Platelet count decreased	Investigations	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Abdominal distension	Gastrointestinal disorders	—
Urinary tract infection	Infections and infestations	—
Infusion related reaction	Injury, poisoning and procedural complications	—
Blood creatinine increased	Investigations	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—
Anxiety	Psychiatric disorders	—
Catarrh	Respiratory, thoracic and mediastinal disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Febrile neutropenia, Sepsis, Anaemia, Atrial fibrillation, Cardiopulmonary failure, Diarrhoea, Gastrointestinal obstruction, Intestinal perforation.

Data from ClinicalTrials.gov NCT02783599 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate potential biomarkers and method of action, efficacy and safety of olaratumab in participants with soft tissue sarcoma (STS).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Systemic treatment in advanced soft tissue sarcoma: what is standard, what is new.
   Frezza AM, Stacchiotti S, Gronchi A. · · 2017 · cited 62× · PMID 28571564 · DOI 10.1186/s12916-017-0872-y
2. Therapeutic approaches targeting molecular signaling pathways common to diabetes, lung diseases and cancer.
   Raguraman R, Srivastava A, Munshi A, Ramesh R. · · 2021 · cited 31× · PMID 34375681 · DOI 10.1016/j.addr.2021.113918
3. PDGF/PDGFR effects in osteosarcoma and the "add-on" strategy.
   Xu J, Xie L, Guo W. · · 2018 · cited 30× · PMID 30083310 · DOI 10.1186/s13569-018-0102-1
4. Heterogeneous Circulating Tumor Cells in Sarcoma: Implication for Clinical Practice.
   Agnoletto C, Caruso C, Garofalo C. · · 2021 · cited 12× · PMID 34063272 · DOI 10.3390/cancers13092189
5. Phase II study of olaratumab with paclitaxel/carboplatin (P/C) or P/C alone in previously untreated advanced NSCLC.
   Gerber DE, Swanson P, Lopez-Chavez A, Wong L, et al · · 2017 · cited 11× · PMID 28838379 · DOI 10.1016/j.lungcan.2017.07.009
6. Olaratumab: a platelet-derived growth factor receptor-α-blocking antibody for the treatment of soft tissue sarcoma.
   Pender A, Jones RL. · · 2017 · cited 8× · PMID 29270033 · DOI 10.2147/cpaa.s130178
7. Spotlight on olaratumab in the treatment of soft-tissue sarcoma: design, development, and place in therapy.
   Davis EJ, Chugh R. · · 2017 · cited 2× · PMID 29263653 · DOI 10.2147/dddt.s121298