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

Lilly

Status and phase: Completed; Phase 1

Conditions: Soft Tissue Sarcoma

Treatments: Drug: Olaratumab; Drug: Pembrolizumab (KEYTRUDA®)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03126591

2016-001949-19 (EudraCT Number)

15847

I5B-MC-JGDQ (Other Identifier)

MK-3475-505 (Other Identifier)

KEYNOTE-505 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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41 participants in 3 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: Olaratumab

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: Olaratumab

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

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab (KEYTRUDA®)

Drug: Olaratumab