Soft Tissue SarcomaPhase 1NCT03126591
A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue Sarcoma
A Phase 1 study testing Olaratumab and Pembrolizumab (KEYTRUDA®) in people with Soft Tissue Sarcoma, run by Eli Lilly and Company at 6 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Olaratumab and Pembrolizumab (KEYTRUDA®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 3 Jul 2017to 21 Feb 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
Belgium1 site
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven, 3000
About this study
Official title: An Open-Label, Multicenter, Phase 1a/1b Study of Olaratumab (LY3012207) Plus Pembrolizumab (MK3475) in Patients With Unresectable Locally Advanced or Metastatic Soft Tissue Sarcoma (STS) Who Have Failed Standard Treatments
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
- Being tested
- Olaratumab, Pembrolizumab (KEYTRUDA®)
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaratumabDrug
Also called LY3012207
Administered IV
Pembrolizumab (KEYTRUDA®)Drug
Also called MK3475
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Olaratumab; Drug: Pembrolizumab (KEYTRUDA®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Cycle 1 (21 Days)
Secondary outcomes (9)
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Maximum observed serum concentration of Olaratumab
Measured: 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
Cmin was the concentration of olaratumab in the sample taken just prior to the following dose.
Measured: 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
Terminal elimination half-life of Olaratumab
Measured: 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
Detection of ADA in the presence of Olaratumab
Measured: 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)
ORR was defined as the percentage of participants who achieved a CR or PR out of all participants treated, measured and recorded by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR was defined as the disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm; tumor marker results must have normalized. PR was defined as at least a 30% decrease in the sum diameter of target lesions (taking as reference the baseline sum diameters). Long term follow up began the day after the safety follow up period was completed.
Measured: Baseline to Measured Progressive Disease (PD) or Start of New Anti-Cancer Therapy (up to 28 months)
Disease Control Rate (DCR): Percentage of Participants With a Best Response of CR, PR or Stable Disease (SD)
DCR was defined according to RECIST v1.1 as the percentage of participants who have achieved CR, PR or stable disease (SD). SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Long term follow up began the day after the safety follow up period was completed.
Measured: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (up to 28 months)
Duration of Response (DoR)
DoR was defined according to RECIST v1.1 as the time from the date of the first CR or PR to the first date of PD or death from any cause, whichever is earlier. For each participant who was not known to have died or to have had a progression of disease as of the data inclusion cut-off date, DOR was censored at the date of last objective response assessment prior to the date of any subsequent systemic anticancer therapy. Long term follow up began the day after the safety follow up period was completed.
Measured: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (up to 24 months)
Progression Free Survival (PFS)
Progression-free survival (PFS) time was defined as the time from the date of start of study treatment to the first date of PD (symptomatic or objective) or death due to any cause, whichever occurs first. For participants who were not known to have died or progressed as of the data-inclusion cut-off date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Long term follow up began the day after the safety follow up period was completed.
Measured: Baseline to Measured Progressive Disease or Death Due to Any Cause (up to 28 months)
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. Data was censored for any participant who was not known to have died or was lost to follow up. Long term follow up began the day after the safety follow up period was completed.
Measured: Baseline to Death from Any Cause (up to 35 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start3 Jul 2017
- Primary completion6 May 2021
- Study completion21 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03126591
- Sponsor's protocol ID
- 15847
- Other IDs
- I5B-MC-JGDQ, 2016-001949-19, KEYNOTE-505, MK-3475-505, 2016
- Status last verified
- Aug 2024
- First submitted
- 17 Apr 2017
- Last updated
- 23 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Phase 1a/1b Study of Olaratumab (LY3012207) Plus Pembrolizumab (MK3475) in Patients With Unresectable Locally Advanced or Metastatic Soft Tissue Sarcoma (STS) Who Have Failed Standard Treatments
- ClinicalTrials.gov ID
- NCT03126591
- Acronym / sponsor ID
- 15847
- Conditions
- Soft Tissue Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 3 Jul 2017 (actual)
- Primary completion
- 6 May 2021 (actual)
- Study completion
- 21 Feb 2023 (actual)
- First posted
- 24 Apr 2017 (actual)
- Results
- Posted 23 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 15 milligrams per kilogram (mg/kg) Olaratumab + 200 milligrams (mg) Pembrolizumab - Dose Escalation | Experimental | Drug: Olaratumab, Drug: Pembrolizumab (KEYTRUDA®)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. |
| 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Escalation | Experimental | Drug: Olaratumab, Drug: Pembrolizumab (KEYTRUDA®)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. |
| 20 mg/kg Olaratumab + 200 mg Pembrolizumab - Dose Expansion | Experimental | Drug: Olaratumab, Drug: Pembrolizumab (KEYTRUDA®)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaratumabAlso: LY3012207Administered IV | Drug | 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®)Also: MK3475Administered IV | Drug | 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 |
Primary outcome
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (21 Days)
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
9 secondary outcomes
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Baseline to Measured Progressive Disease (PD) or Start of New Anti-Cancer Therapy (up to 28 months)
Disease Control Rate (DCR): Percentage of Participants With a Best Response of CR, PR or Stable Disease (SD)
Time frame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (up to 28 months)
Duration of Response (DoR)
Time frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (up to 24 months)
Progression Free Survival (PFS)
Time frame: Baseline to Measured Progressive Disease or Death Due to Any Cause (up to 28 months)
Overall Survival (OS)
Time frame: Baseline to Death from Any Cause (up to 35 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Study of Olaratumab (LY3012207) Plus Pembrolizumab in Participants With Advanced or Metastatic Soft Tissue SarcomaLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaratumab and Pembrolizumab (KEYTRUDA®) in people with Soft Tissue Sarcoma, run by Eli Lilly and Company at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Belgium, Denmark, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Olaratumab Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (21 Days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2024.