CLINICAL TRIALS PROFILE FOR OLARATUMAB

All Clinical Trials for olaratumab

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00913835 ↗	A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer	Completed	Eli Lilly and Company	Phase 2	2009-06-01	The purpose of this study is to determine if participants with platinum-refractory or platinum-resistant advanced ovarian cancer have a better outcome when treated with Olaratumab (IMC-3G3) in combination with Liposomal Doxorubicin than when treated with Liposomal Doxorubicin alone.
NCT00918203 ↗	A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)	Completed	Eli Lilly and Company	Phase 2	2010-01-01	The purpose of this study is to determine if participants with untreated locally advanced or metastatic non-small cell lung cancer have a better outcome when treated with olaratumab in combination with paclitaxel/carboplatin then when treated with paclitaxel/carboplatin alone.
NCT01185964 ↗	A Study of Olaratumab in Soft Tissue Sarcoma	Completed	Eli Lilly and Company	Phase 1/Phase 2	2010-10-01	The main purpose of this study is to gather information about the use of an investigational drug called olaratumab with a drug for soft tissue sarcoma called doxorubicin.
NCT01204710 ↗	A Study of Olaratumab (IMC-3G3) in Prostate Cancer	Completed	Eli Lilly and Company	Phase 2	2010-10-01	This is a study evaluating the safety and efficacy of the monoclonal antibody olaratumab plus mitoxantrone plus prednisone compared to mitoxantrone plus prednisone in metastatic castration-refractory prostate cancer following disease progression or intolerance on docetaxel-based chemotherapy.
NCT02326025 ↗	A Study of Olaratumab and Doxorubicin in Participants With Advanced Soft Tissue Sarcoma	Completed	Eli Lilly and Company	Phase 1	2015-01-22	The purpose of this study is to assess how the body handles olaratumab when it is given with another drug called doxorubicin. The safety and tolerability of these drugs will be studied. Each participant will complete two 21-day cycles in a fixed order. Participants who complete Cycle 2 may continue to receive olaratumab + doxorubicin for an additional six 21-day cycles and then may receive olaratumab alone until discontinuation criteria are met. Screening is required within 21 days prior to first dose. Part B was added in October, 2015 to assess how the body handles a higher dose of olaratumab when given with doxorubicin. Participants may only enroll in one part.
NCT02377752 ↗	A Study of Olaratumab in Japanese Participants With Advanced Cancer	Completed	Eli Lilly and Company	Phase 1	2015-03-23	This study consists of 2 parts (Part A and Part B). The main purpose of Part A is to evaluate safety and side effects of olaratumab in combination with doxorubicin in Japanese participants with a group of rare cancers (advanced solid tumors, especially advanced soft tissue sarcoma [STS].) The main purpose of Part B is to evaluate how much olaratumab gets into the blood stream of Japanese participants with advanced solid tumors and how long it takes the body to get rid of it.

Clinical Trial Conditions for olaratumab

Condition Name

Condition Name for olaratumab
Intervention	Trials
Soft Tissue Sarcoma	8
Sarcoma, Soft Tissue	4
Leiomyosarcoma	3
Liposarcoma	2

Condition MeSH

Condition MeSH for olaratumab
Intervention	Trials
Sarcoma	14
Leiomyosarcoma	3
Liposarcoma	2
Hemangiosarcoma	1

Clinical Trial Locations for olaratumab

Trials by Country

Trials by Country for olaratumab
Location	Trials
United States	137
Germany	11
Italy	8
Spain	6
United Kingdom	6

Trials by US State

Trials by US State for olaratumab
Location	Trials
New York	9
Florida	9
Texas	8
Missouri	8
California	8

Clinical Trial Progress for olaratumab

Clinical Trial Phase

Clinical Trial Phase for olaratumab
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	6
Phase 1/Phase 2	5

Clinical Trial Status

Clinical Trial Status for olaratumab
Clinical Trial Phase	Trials
Completed	11
Active, not recruiting	7
Recruiting	1

Clinical Trial Sponsors for olaratumab

Sponsor Name

Sponsor Name for olaratumab
Sponsor	Trials
Eli Lilly and Company	13
Taipei Veterans General Hospital, Taiwan	1
Washington University School of Medicine	1

Sponsor Type

Sponsor Type for olaratumab
Sponsor	Trials
Industry	17
Other	13

Olaratumab: A Comprehensive Review of Clinical Trials, Market Analysis, and Projections

Last updated: January 17, 2025

Introduction

Olaratumab, marketed as Lartruvo, is a monoclonal antibody developed by Eli Lilly and Company for the treatment of soft tissue sarcoma (STS). Here, we will delve into the clinical trials, market analysis, and the eventual withdrawal of olaratumab from the market.

Mechanism of Action

Olaratumab is a recombinant, fully human IgG subclass 1 monoclonal antibody that targets the platelet-derived growth factor receptor-alpha (PDGFR-α). By binding to PDGFR-α, olaratumab blocks the downstream signaling induced by ligands PDGF-AA, -BB, and -CC, potentially inhibiting the growth-promoting signals in cancer cells[3][4].

Initial Approval and Clinical Trials

In October 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval to olaratumab in combination with doxorubicin for the treatment of patients with STS not amenable to curative treatment with radiotherapy or surgery. This approval was based on a randomized phase II clinical trial involving 133 patients, which showed a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) for patients receiving the combination treatment compared to those receiving doxorubicin alone[1][3].

Phase II Trial Results

• Overall Survival: Median OS was 26.5 months for the combination group versus 14.7 months for the doxorubicin-alone group.
• Progression-Free Survival: Median PFS was 8.2 months for the combination group and 4.4 months for the doxorubicin-alone group.
• Overall Response Rate: 18% in the combination arm versus 8% in the doxorubicin-alone arm[1].

Phase III ANNOUNCE Trial

As a condition of the accelerated approval, Eli Lilly was required to conduct a phase III clinical trial, known as the ANNOUNCE trial, to confirm the clinical benefit of olaratumab in combination with doxorubicin. This trial compared doxorubicin plus olaratumab to doxorubicin plus placebo in patients with locally advanced or metastatic STS.

Phase III Trial Results

The ANNOUNCE trial failed to confirm the clinical benefit of adding olaratumab to doxorubicin. The trial did not show a significant difference in overall survival between the two treatment arms. Specifically:

• Overall Survival: No statistically significant difference was observed between the doxorubicin plus olaratumab group and the doxorubicin plus placebo group (median OS: 20.4 months vs 19.7 months)[4][5].

Market Withdrawal

Following the disappointing results of the ANNOUNCE trial, Eli Lilly announced the withdrawal of olaratumab from the market for the treatment of advanced STS in October 2019. This decision was made due to the failure of the drug to meet the primary endpoint of overall survival in the phase III trial[3][5].

Post-Withdrawal Access Program

To ensure minimal disruption for patients already on the treatment, Eli Lilly established an access program. Patients who were currently receiving olaratumab could continue their treatment, subject to local laws and regulations, after consulting with their physicians about the associated risks. However, no new patients were permitted to start treatment outside of ongoing clinical trials[5].

Market Analysis

The withdrawal of olaratumab from the market had significant implications for the treatment landscape of STS. Here are some key points:

Impact on STS Treatment

• The failure of olaratumab to demonstrate a clinical benefit in the phase III trial left a gap in the treatment options for patients with advanced STS.
• Other treatments, such as doxorubicin alone or in combination with other agents, remain the standard of care for these patients[3][5].

Financial Implications

• The withdrawal likely had financial implications for Eli Lilly, as it represented a significant investment in research and development.
• The market for STS treatments is relatively small compared to other cancer types, but the failure of olaratumab still had a notable impact on the company's portfolio[5].

Future Prospects and Alternative Uses

Despite its withdrawal for STS, olaratumab is being explored for other potential uses:

Radiopharmaceutical Development

Telix Pharmaceuticals Limited has licensed olaratumab from Eli Lilly and is developing radiolabelled forms of the antibody for diagnostic and therapeutic purposes. Preclinical studies have shown promising results, and the company is moving forward with first-in-human clinical trials[2].

Side Effects and Safety Profile

During its clinical use, olaratumab was associated with several side effects, including:

• Nausea
• Fatigue
• Neutropenia
• Musculoskeletal pain
• Mucositis
• Alopecia
• Vomiting
• Diarrhea
• Decreased appetite
• Abdominal pain
• Neuropathy
• Headache
• Infusion-related reactions in 13% of patients[1].

Key Takeaways

• Olaratumab was initially approved for STS based on promising phase II trial results but failed to confirm its clinical benefit in the phase III ANNOUNCE trial.
• The drug was withdrawn from the market in 2019 due to lack of efficacy.
• Despite this, olaratumab is being explored for other therapeutic and diagnostic applications.
• The withdrawal highlights the challenges and risks associated with drug development, particularly in rare and complex diseases like STS.

FAQs

Q: What is olaratumab, and how does it work?

A: Olaratumab is a monoclonal antibody that targets the platelet-derived growth factor receptor-alpha (PDGFR-α), blocking growth-promoting signals in cancer cells.

Q: Why was olaratumab withdrawn from the market?

A: Olaratumab was withdrawn due to the failure of the phase III ANNOUNCE trial to confirm its clinical benefit in improving overall survival for patients with advanced soft tissue sarcoma.

Q: What were the key findings of the phase III ANNOUNCE trial?

A: The trial did not show a significant difference in overall survival between patients treated with doxorubicin plus olaratumab and those treated with doxorubicin plus placebo.

Q: What are the current and future prospects for olaratumab?

A: Despite its withdrawal for STS, olaratumab is being developed for other uses, including as a radiopharmaceutical for diagnostic and therapeutic purposes.

Q: What side effects were associated with olaratumab treatment?

A: Common side effects included nausea, fatigue, neutropenia, musculoskeletal pain, and infusion-related reactions, among others.

Sources

1. FDA: Olaratumab (LARTRUVO)[1].
2. PR Newswire: Olaratumab Antibody Licensed from Lilly Demonstrates Proof-of-Concept as a Theranostic Radiopharmaceutical[2].
3. NCI Staff: New Treatment Approved for Soft Tissue Sarcoma[3].
4. JAMA: Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo in Patients With Advanced Soft Tissue Sarcoma[4].
5. Targeted Oncology: Olaratumab to Be Withdrawn From Market for Soft Tissue Sarcoma After Missing Primary Endpoint[5].