A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma

NCT03126591 | Completed Phase 1 Results FDA Drug

• 5 other identifiers: 15847I5B-MC-JGDQ2016-001949-19KEYNOTE-505MK-3475-505
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the safety of olaratumab plus pembrolizumab in participants with previously treated advanced or metastatic soft tissue sarcoma.

Conditions

Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)

  A DLT was defined as an adverse event (AE) during Cycle 1 that is possibly related to the study drug and fulfills any 1 of the following criteria using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0: * Grade ≥3 nonhematologic toxicity, with exceptions * Grade 4 anemia * Grade 4 neutropenia or leukopenia of \>5 days duration * Febrile neutropenia * Grade 3 thrombocytopenia with clinically significant bleeding or Grade 4 thrombocytopenia * Any other significant toxicity deemed to be dose limiting

  Cycle 1 (21 Days)

Secondary Outcomes (9)

• Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab

  Cycle 1 and Cycle 3 Day (D) 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose

• PK: Minimum Serum Concentration (Cmin) of Olaratumab

  Cycle 1 and Cycle 3 Day 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose

• PK: Elimination Half-Life (t½) of Olaratumab

  Cycle 1 and Cycle 3 Day 1: Predose, 1, 2, 5, 24, 96, 168 hours Postdose; Cycle 1 and Cycle 3 Day 8: Predose, 1, 2, 5, 48, 168, 336 hours Postdose

• Number of Participants With Anti-Olaratumab Antibodies (ADA) When Administered in Combination With Pembrolizumab

  Predose Cycle 1 Day 1 through Follow Up (up to 6 months)

• Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)

  Baseline to Measured Progressive Disease (PD) or Start of New Anti-Cancer Therapy (up to 28 months)

Study Arms (3)

15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation

EXPERIMENTAL

Participants received15 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.

Drug: Olaratumab; Drug: Pembrolizumab (KEYTRUDA®)

20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation

EXPERIMENTAL

Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.

Drug: Olaratumab; Drug: Pembrolizumab (KEYTRUDA®)

20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion

EXPERIMENTAL

Participants received 20 mg/kg Olaratumab administered IV on Day 1 and Day 8 in addition to 200 mg Pembrolizumab administered IV on Day 1 of a 21-day cycle.

Drug: Olaratumab; Drug: Pembrolizumab (KEYTRUDA®)

Interventions

Olaratumab DRUG

Administered IV

Also known as: LY3012207

15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation; 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation; 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion

Pembrolizumab (KEYTRUDA®) DRUG

Administered IV

Also known as: MK3475

15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation; 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation; 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of advanced unresectable or metastatic STS, not amenable to curative treatment and after available standard therapies have failed to provide clinical benefit. Note: Participants with a diagnosis of Grade 1 liposarcoma (atypical lipomatous neoplasms) are eligible if there is histological or radiographic evidence of evolution to more aggressive disease.
• Presence of measurable or nonmeasurable but evaluable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Must be able to provide tumor tissue obtained within 6 months of study enrollment. If such tissue is not available, a newly obtained core or excisional biopsy of a tumor lesion must be performed.
• Have an anticipated life expectancy of ≥3 months.

You may not qualify if:

• Have received any previous systemic therapy (including investigational agents) targeting PD-1/programmed cell death ligand 1 (PDL-1) or PD-1/PDL-2 signaling pathways (including previous participation in Merck MK-3475 trials). Prior treatment with olaratumab is allowed. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, is not permitted.
• Have known active central nervous system (CNS) metastasis and/or carcinomatous meningitis. Participants with treated CNS metastases are eligible for this study if they have not received corticosteroids and/or anticonvulsants within 7 days of study treatment, and their disease is asymptomatic and radiographically stable for at least 60 days.
• Have active autoimmune disease or other syndrome that requires systemic steroids or autoimmune agents in the past 2 years.
• History of interstitial lung disease or non-infectious pneumonia.
• Have received a live-virus vaccine within 30 days prior to planned treatment start.
• Have histologically or cytologically confirmed Kaposi's sarcoma or gastrointestinal stromal tumor (GIST).
• Have inflammatory bowel disease for which the participant has used immunosuppressive agents within the last 2 years.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

Gustave Roussy

Villejuif, 94805, France

Location

Related Links

• A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma

MeSH Terms

Conditions

Sarcoma

Interventions

olaratumab; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2017
• First Posted: April 24, 2017
• Study Start: July 3, 2017
• Primary Completion: May 6, 2021
• Study Completion: February 21, 2023
• Last Updated: October 23, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-08

Locations

US (3); BE (1); DK (1); FR (1)