SarcomaPhase 2PEMBROSARCNCT02406781

Combination of MK3475 and Metronomic Cyclophosphamide in Patients With Advanced Sarcomas : Multicentre Phase II Trial

A Phase 2 study testing Combination of MK3475 with Metronomic CP and Combination of MK3475 with Metronomic CP and G100 in people with Sarcoma, run by Institut Bergonié at 8 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multicenter study assessing the efficacy of different therapeutic strategy in patients with advanced sarcomas. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Sarcoma
What is being tested?: Combination of MK3475 with Metronomic CP and Combination of MK3475 with Metronomic CP and G100
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 129 participants
Where: 8 sitesFrance
Study dates: Jun 2015to 15 Jan 2023
Phase: Phase 2
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

Histology : Leiomyosarcoma, or UPS, or other sarcoma, or GIST or osteosarcoma, or soft-tissue sarcoma with presence of tertiary lymphoid structures (stratum 6) histologically confirmed by central review.
Advanced non resectable / metastatic disease for strata 1 to 6. For stratum 7: locally advanced or metastatic disease with at least one injectable lesion.
Documented progression according to RECIST criteria. Progression on the last line of treatment should be confirmed by central review with two radiological assessments identical obtained at less than 6 months interval within the 12 months before inclusion.
For stratum 5, documented disease progression according to RECIST criteria after the first line imatinib and second line sunitinib.
Have provided tissue of a tumor lesion from an archival tissue sample obtained on metastasis or on locally advanced disease, or newly obtained core or excisional biopsy. For strata 6 and 7, tissue < 3 months old and with no subsequent treatment since or from a newly obtained biopsy.
For strata 1, 2, 3 and 6: no more of four previous lines of systemic therapy for metastatic disease and no more than 2 previous line for stratum 7.

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Age ≥ 18 years.
ECOG performance status ≤ 1.
Measurable disease according to RECIST v1.1 outside any previously irradiated field. At least one site of disease must be uni-dimensionally ≥ 10 mm.
Life expectancy > 3 months (except for stratum 7 > 6 months).
≥ 1 previous line (s) of chemotherapy in the palliative setting for strata 1 to 5. For other strata, participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement.
No symptomatic central nervous system disease.
No chronic use of glucocorticoids.
Adequate hematological, renal, metabolic and hepatic function:
Hemoglobin ≥ 9 g/dl (patients may have received prior red blood cell transfusion); ANC ≥ 1.5 x 109/l and platelet count ≥ 100 x 109/l. For stratum 7: lymphocyte count ≥ 0.5.109 /l
ALT and AST ≤ 2.5 x upper limit of normality (ULN) (≤ 5 in case of liver metastasis)
Total bilirubin ≤ 1.5 x ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels ≥ 1.5 x ULN
Albumin ≥ 25g/l
Serum creatinine ≤ 1.5 x ULN OR CrCl ≥ 60 ml/min for subject with creatinine levels ≥ 1.5 x ULN,
Creatine phosphokinase ≤ 2.5 x ULN
INR ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
aPTT ≤ 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma.
At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy.
Recovery to grade ≤ 1 from any adverse event from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade ≤ 2 (NCI-CTCAE, v 4.0).
Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for four months after discontinuation of treatment. Acceptable methods for contraception include intrauterine device, oral contraceptive, subdermal implant and double barrier. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥ 1 year.
Voluntary signed and dated written informed consents prior to any specific study procedure.
Patients with a French social security in compliance with the Law relating to biomedical research (Article 1121-11 of French Public Health Code).

Who cannot join

Previous treatment with MK3475 or CP or G100.
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
Participation to a study involving a medical or therapeutic intervention in the last 30 days.
Previous enrolment in the present study.

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Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons.
Known hypersensitivity to any involved study drug or of its formulation components.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjorgen's syndrome will not be excluded from the study.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Has known active hepatitis B or hepatitis C.
Has a known history of HIV (HIV1/2 antibodies).
Has received a live vaccine within 30 days prior to the first dose of trial treatment.
For strata 6 to 7:
patients with oral anticoagulation therapy
known urinary tract obstruction
previous allogenic bone marrow transplant
has an active infection requiring systemic treatment within 14 days prior to study

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

France8 sites

Institut Bergonié
Bordeaux, 33076
Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard
Lyon, 69373
Institut Paoli Calmettes
Marseille, 13273
Institut Curie
Paris, 75005
Institut de Cancérologie de l'Ouest
Saint-Herblain, 44805
Institut Claudius Regaud
Toulouse, 31052
Institut Gustave Roussy
Villejuif, 94800

Other trials in France

About this study

This is a multicenter study assessing the efficacy of different therapeutic strategy in patients with advanced sarcomas.

Read the detailed description

This is a phase 2 trial with 7 strata :

Leiomyosarcoma (strata 1) : 33 patients
Undifferentiated sarcoma (strata 2): 33 patients
Sarcomas others (strata 3) : 33 patients
Osteosarcoma (strata 4) : 33 patients
GIST (strata 5): 31 patients
Advanced soft-tissue sarcoma with immune signature (strata 6): 32 patients
Metastatic soft-tissue sarcoma (strata 7): 32 patients

Conditions: Sarcoma
Being tested: Combination of MK3475 with Metronomic CP, Combination of MK3475 with Metronomic CP and G100
Keywords: Efficacy of MK 3475 with Metronomic Cyclophosphamide, Advanced Sarcomas, Leiomyosarcoma, Undifferentiated Sarcoma, Other Sarcoma, GIST, Osteosarcoma
Medical subject headings: Sarcoma, Leiomyosarcoma, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Combination of MK3475 with Metronomic CPDrug
Also called Pembrolizumab, Endoxan
Combination of MK3475 with Metronomic CP. Metronomic CP (cyclophosphamide) will be administered per os bi-daily (50 mg x 2), and given on a week on/ week off schedule.
MK3475 will be administered intraveinously, and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.
Combination of MK3475 with Metronomic CP and G100Drug
Also called Pembrolizumab, Endoxan, GLA-SE (glucopyranosyl lipid adjuvant-stable emulsion).
Combination of MK3475 with Metronomic CP and G100. Metronomic CP (cyclophosphamide) will be administered per os bi-daily (50 mg x 2), and given on a week on/ week off schedule.
MK3475 will be administered intravenously (200 mg), and given every 3 weeks on day 8.
G100 will be administered by intra-tumoral injection (20µg), one weekly injection for at least 6 weeks and for a maximum of 12 weeks. G100 will start one week before CP administration (impregnation phase).
A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.

Study groups in NCT02406781
Study group	Role	What they receive
Stratum 1: Advanced Leiomyosarcoma	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced leiomyosarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 2: Advanced undifferentiated sarcoma	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced undifferentiated sarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 3: Advanced other sarcoma	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced other sarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 4: Advanced osteosarcoma	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced osteosarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 5: Advanced GIST	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced GIST. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 6: Advanced soft-tissue sarcomas with immune signature	Experimental	Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced soft-tissue sarcomas with immune signature. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. Receives: Drug: Combination of MK3475 with Metronomic CP
Stratum 7: Metastatic soft-tissue sarcoma.	Experimental	Treatment strategy B: Combination of MK3475 with Metronomic CP and G100 adminitrered to patients with metastatic soft-tissue sarcoma. MK3475 will be administered intravenously. Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. Receives: Drug: Combination of MK3475 with Metronomic CP and G100

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants in Objective Response at 6 Months
Objective response is defined according to RECIST v1.1 as either complete response (disappearance of all target lesions, with any pathological lymph nodes reduced in short axis to <10 mm) or partial response (≥30% decrease in the sum of diameters of target lesions compared with baseline).
This primary endpoint is part of a dual endpoint encompassing both non-progression and objective response at 6 months (non-progression is presented as a separate primary outcome). ORR at 6 months will be evaluated only in the following strata: Stratum 1: Advanced leiomyosarcoma ; Stratum 2: Advanced undifferentiated sarcoma ; Stratum 3: Advanced other sarcoma ; Stratum 4: Advanced osteosarcoma
Measured: 6 months from treatment initiation
Percentage of Particpants in Non-progression at 6 Months
Non-progression is defined as the absence of progressive disease according to RECIST v1.1. Progressive disease defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
This outcome will be assessed as a stand-alone primary endpoint in the following strata: Stratum 5: Advanced gastrointestinal stromal tumor (GIST) ; Stratum 6: Advanced soft tissue sarcomas with immune signature ; Stratum 7: Metastatic soft tissue sarcoma (STS)
In strata 1 to 4, non-progression is considered as part of the dual primary endpoint together with objective response at 6 months.
Measured: 6 months from treatment initiation

Secondary outcomes (3)

Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1.
Best overall response is defined as the best response across all time points (RECIST v1.1). The best overall response is determined once all the data for the participant is known.
Each patient has been assigned one of the following categories (RECIST 1.1): complete response (disappearance of all target lesions); partial response (>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); progression (20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and stable disease (nor CR, PR or progression).
Measured: 6 months from treatment initiation
Median Progression-free Survival
Progression-free survival (PFS) is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first.
Progressive disease defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Patients alive and progression free were censored at the date of last follow-up, death, or last patient contact. Progression is assessed as per RECIST v1.1.
Progression-free survival is estimated as a function of time using Kaplan-Meier method.
Measured: From start of treatment, and during treatment until progression or death for any cause, whichever occurs first, for up to 12 months.
Median Overall Survival
Overall survival (OS) defined as the time from randomization to death (due to any cause). Patients alive were censored at the date of last follow-up or last patient contact. Overall survival was estimated as a function of time using Kaplan-Meier method.
Measured: From start of treatment, and during treatment until death for any cause for up to 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 201515 Jan 2023

First posted2 Apr 2015 (estimated)
Study startJun 2015
Primary completion24 Nov 2020
Study completion15 Jan 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.
Publications (6)Papers the sponsor has linked to this study.
Other trials for SarcomaStudies of the same condition, open and under way.
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 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 129 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02406781
Sponsor's protocol ID: IB 2014-04
Other IDs: 2014-004568-39, 2014
Acronym: PEMBROSARC
Status last verified: Nov 2025
First submitted: 12 Mar 2015
Last updated: 10 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Toulmonde M, Penel N, Adam J, Chevreau C, Blay JY, Le Cesne A, Bompas E, Piperno-Neumann S, Cousin S, Grellety T, Ryckewaert T, Bessede A, Ghiringhelli F, Pulido M, Italiano A. Use of PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Sarcomas: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jan 1;4(1):93-97. doi: 10.1001/jamaoncol.2017.1617.
PubMed 28662235
Italiano A, Bessede A, Pulido M, Bompas E, Piperno-Neumann S, Chevreau C, Penel N, Bertucci F, Toulmonde M, Bellera C, Guegan JP, Rey C, Sautes-Fridman C, Bougouin A, Cantarel C, Kind M, Spalato M, Dadone-Montaudie B, Le Loarer F, Blay JY, Fridman WH. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat Med. 2022 Jun;28(6):1199-1206. doi: 10.1038/s41591-022-01821-3. Epub 2022 May 26.
PubMed 35618839
Spalato-Ceruso M, Bouteiller F, Guegan JP, Toulmonde M, Bessede A, Kind M, Cousin S, Buy X, Palussiere J, Le Loarer F, Dadone-Montaudie B, Pulido M, Italiano A. Pembrolizumab combined with low-dose cyclophosphamide and intra-tumoral injection of the toll-like receptor 4 agonist G100 in patients with advanced pretreated soft tissue sarcoma: results from the PEMBROSARC basket study. J Hematol Oncol. 2022 Oct 27;15(1):157. doi: 10.1186/s13045-022-01377-2.
PubMed 36303228
Sun CM, Toulmonde M, Spalato-Ceruso M, Peyraud F, Bessede A, Kind M, Cousin S, Buy X, Palussiere J, Bougouin A, Sautes-Fridman C, Fridman HW, Pulido M, Italiano A. Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study. Mol Cancer. 2024 Feb 19;23(1):37. doi: 10.1186/s12943-024-01942-y.
PubMed 38374062
Le Cesne A, Marec-Berard P, Blay JY, Gaspar N, Bertucci F, Penel N, Bompas E, Cousin S, Toulmonde M, Bessede A, Fridman WH, Sautes-Fridman C, Kind M, Le Loarer F, Pulido M, Italiano A. Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study. Eur J Cancer. 2019 Sep;119:151-157. doi: 10.1016/j.ejca.2019.07.018. Epub 2019 Aug 21.
PubMed 31442817
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 10 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Combination of MK3475 and Metronomic Cyclophosphamide in Patients With Advanced Sarcomas : Multicentre Phase II Trial
ClinicalTrials.gov ID: NCT02406781
Acronym / sponsor ID: PEMBROSARC / IB 2014-04
Conditions: Sarcoma
Keywords: Efficacy of MK 3475 with Metronomic Cyclophosphamide, Advanced Sarcomas, Leiomyosarcoma, Undifferentiated Sarcoma, Other Sarcoma, GIST, Osteosarcoma
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 129 participants (actual)
Lead sponsor: Institut BergoniéUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC, Ministry of Health, France, Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study start: Jun 2015 (actual)
Primary completion: 24 Nov 2020 (actual)
Study completion: 15 Jan 2023 (actual)
First posted: 2 Apr 2015 (estimated)
Results: Posted 10 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This is a multicenter study assessing the efficacy of different therapeutic strategy in patients with advanced sarcomas.

Detailed description

This is a phase 2 trial with 7 strata :

Leiomyosarcoma (strata 1) : 33 patients
Undifferentiated sarcoma (strata 2): 33 patients
Sarcomas others (strata 3) : 33 patients
Osteosarcoma (strata 4) : 33 patients
GIST (strata 5): 31 patients
Advanced soft-tissue sarcoma with immune signature (strata 6): 32 patients
Metastatic soft-tissue sarcoma (strata 7): 32 patients

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 7

Arm	Type	Receives
Stratum 1: Advanced Leiomyosarcoma	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced leiomyosarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 2: Advanced undifferentiated sarcoma	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced undifferentiated sarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 3: Advanced other sarcoma	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced other sarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 4: Advanced osteosarcoma	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced osteosarcoma. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 5: Advanced GIST	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced GIST. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 6: Advanced soft-tissue sarcomas with immune signature	Experimental	Drug: Combination of MK3475 with Metronomic CPTreatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced soft-tissue sarcomas with immune signature. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally.
Stratum 7: Metastatic soft-tissue sarcoma.	Experimental	Drug: Combination of MK3475 with Metronomic CP and G100Treatment strategy B: Combination of MK3475 with Metronomic CP and G100 adminitrered to patients with metastatic soft-tissue sarcoma. MK3475 will be administered intravenously. Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (28 listed)

Histology : Leiomyosarcoma, or UPS, or other sarcoma, or GIST or osteosarcoma, or soft-tissue sarcoma with presence of tertiary lymphoid structures (stratum 6) histologically confirmed by central review.
Advanced non resectable / metastatic disease for strata 1 to 6. For stratum 7: locally advanced or metastatic disease with at least one injectable lesion.
Documented progression according to RECIST criteria. Progression on the last line of treatment should be confirmed by central review with two radiological assessments identical obtained at less than 6 months interval within the 12 months before inclusion.
For stratum 5, documented disease progression according to RECIST criteria after the first line imatinib and second line sunitinib.
Have provided tissue of a tumor lesion from an archival tissue sample obtained on metastasis or on locally advanced disease, or newly obtained core or excisional biopsy. For strata 6 and 7, tissue < 3 months old and with no subsequent treatment since or from a newly obtained biopsy.

Key exclusion criteria (19 listed)

Previous treatment with MK3475 or CP or G100.
Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases.
Men or women of childbearing potential who are not using an effective method of contraception as previously described; women who are pregnant or breast feeding.
Participation to a study involving a medical or therapeutic intervention in the last 30 days.

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
Combination of MK3475 with Metronomic CPAlso: Pembrolizumab, EndoxanCombination of MK3475 with Metronomic CP. Metronomic CP (cyclophosphamide) will be administered per os bi-daily (50 mg x 2), and given on a week on/ week off schedule. MK3475 will be administered intraveinously, and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.	Drug	Stratum 1: Advanced Leiomyosarcoma, Stratum 2: Advanced undifferentiated sarcoma, Stratum 3: Advanced other sarcoma, Stratum 4: Advanced osteosarcoma, Stratum 5: Advanced GIST, Stratum 6: Advanced soft-tissue sarcomas with immune signature
Combination of MK3475 with Metronomic CP and G100Also: Pembrolizumab, Endoxan, GLA-SE (glucopyranosyl lipid adjuvant-stable emulsion).Combination of MK3475 with Metronomic CP and G100. Metronomic CP (cyclophosphamide) will be administered per os bi-daily (50 mg x 2), and given on a week on/ week off schedule. MK3475 will be administered intravenously (200 mg), and given every 3 weeks on day 8. G100 will be administered by intra-tumoral injection (20µg), one weekly injection for at least 6 weeks and for a maximum of 12 weeks. G100 will start one week before CP administration (impregnation phase). A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.	Drug	Stratum 7: Metastatic soft-tissue sarcoma.

Primary outcome

Percentage of Participants in Objective Response at 6 Months
Time frame: 6 months from treatment initiation
Objective response is defined according to RECIST v1.1 as either complete response (disappearance of all target lesions, with any pathological lymph nodes reduced in short axis to <10 mm) or partial response (≥30% decrease in the sum of diameters of target lesions compared with baseline). This primary endpoint is part of a dual endpoint encompassing both non-progression and objective response at 6 months (non-progression is presented as a separate primary outcome). ORR at 6 months will be evaluated only in the following strata: Stratum 1: Advanced leiomyosarcoma ; Stratum 2: Advanced undifferentiated sarcoma ; Stratum 3: Advanced other sarcoma ; Stratum 4: Advanced osteosarcoma
Percentage of Particpants in Non-progression at 6 Months
Time frame: 6 months from treatment initiation
Non-progression is defined as the absence of progressive disease according to RECIST v1.1. Progressive disease defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). This outcome will be assessed as a stand-alone primary endpoint in the following strata: Stratum 5: Advanced gastrointestinal stromal tumor (GIST) ; Stratum 6: Advanced soft tissue sarcomas with immune signature ; Stratum 7: Metastatic soft tissue sarcoma (STS) In strata 1 to 4, non-progression is considered as part of the dual primary endpoint together with objective response at 6 months.

3 secondary outcomes

Percentage of Patients Remaining Alive With Best Overall Response as Per RECIST v1.1.
Time frame: 6 months from treatment initiation
Median Progression-free Survival
Time frame: From start of treatment, and during treatment until progression or death for any cause, whichever occurs first, for up to 12 months.
Median Overall Survival
Time frame: From start of treatment, and during treatment until death for any cause for up to 30 months

Results and safety

Results posted to the registry on 10 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Stratum 1: Advanced Leiomyosarcoma	15	13
Stratum 2: Advanced Undifferentiated Sarcoma	16	14
Stratum 3: Advanced Other Sarcoma	16	14
Stratum 4: Advanced GIST	17	15
Stratum 5: Advanced Soft-tissue Sarcomas	10	9
Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature	35	30
Stratum 7: Metastatic Soft-tissue Sarcoma.	20	17

Primary outcome: Percentage of Participants in Objective Response at 6 Months

Time frame: 6 months from treatment initiation. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Stratum 1: Advanced Leiomyosarcoma n = 13	Stratum 2: Advanced Undifferentiated Sarcoma n = 14	Stratum 3: Advanced Other Sarcoma n = 14	Stratum 4: Advanced Osteosarcoma n = 15
Value	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)	6.7 (0.2 to 32.0)

Population analysed: Population eligible and assessable for the primary endpoint: eligible patients who received at least one administration of PEMBROLIZUMAB and one administration of Metronomic CP.

Primary outcome: Percentage of Particpants in Non-progression at 6 Months

Time frame: 6 months from treatment initiation. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Stratum 1: Advanced Leiomyosarcoma n = 13	Stratum 2: Advanced Undifferentiated Sarcoma n = 14	Stratum 3: Advanced Other Sarcoma n = 14	Stratum 4: Advanced GIST n = 15	Stratum 5: Advanced Soft-tissue Sarcomas n = 9	Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature n = 30	Stratum 7: Metastatic Soft-tissue Sarcoma. n = 17
Value	0.0 (0.0 to 0.0)	7.1 (0.2 to 33.9)	14.3 (1.8 to 42.8)	13.3 (1.7 to 40.5)	11.1 (2.8 to 48.3)	40 (22.7 to 59.4)	11.8 (1.5 to 36.4)

Population analysed: Population eligible and assessable for the primary endpoint: eligible patients who received at least: * For all strata (except for stratum 7): one administration of PEMBROLIZUMAB and one administration of Metronomic CP * For stratum 7: one administration of PEMBROLIZUMAB and one administration of Metronomic CP and one administration of G100.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (serious and non-serious) and deaths were reported for 90 days after the last treatment administration or until the start of a new antitumor therapy, whichever occurs first, up to 30 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stratum 1: Advanced Leiomyosarcoma	5 of 15 (33.3%)	15 of 15 (100%)	13 of 15
Stratum 2: Advanced Undifferentiated Sarcoma	10 of 16 (62.5%)	16 of 16 (100%)	14 of 16
Stratum 3: Advanced Other Sarcoma	9 of 16 (56.3%)	16 of 16 (100%)	7 of 16
Stratum 4: Advanced GIST	12 of 16 (75%)	16 of 16 (100%)	12 of 16
Stratum 5: Advanced Soft-tissue Sarcomas	9 of 10 (90%)	10 of 10 (100%)	3 of 10
Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature	14 of 35 (40%)	35 of 35 (100%)	15 of 35
Stratum 7: Metastatic Soft-tissue Sarcoma.	8 of 19 (42.1%)	19 of 19 (100%)	9 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28662235Toulmonde M, Penel N, Adam J, Chevreau C, Blay JY, Le Cesne A, Bompas E, Piperno-Neumann S, Cousin S, Grellety T, Ryckewaert T, Bessede A, Ghiringhelli F, Pulido M, Italiano A. Use of PD-1 Targeting, Macrophage Infiltration, and IDO Pathway Activation in Sarcomas: A Phase 2 Clinical Trial. JAMA Oncol. 2018 Jan 1;4(1):93-97. doi: 10.1001/jamaoncol.2017.1617.
Results publication: PubMed 35618839Italiano A, Bessede A, Pulido M, Bompas E, Piperno-Neumann S, Chevreau C, Penel N, Bertucci F, Toulmonde M, Bellera C, Guegan JP, Rey C, Sautes-Fridman C, Bougouin A, Cantarel C, Kind M, Spalato M, Dadone-Montaudie B, Le Loarer F, Blay JY, Fridman WH. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat Med. 2022 Jun;28(6):1199-1206. doi: 10.1038/s41591-022-01821-3. Epub 2022 May 26.
Results publication: PubMed 36303228Spalato-Ceruso M, Bouteiller F, Guegan JP, Toulmonde M, Bessede A, Kind M, Cousin S, Buy X, Palussiere J, Le Loarer F, Dadone-Montaudie B, Pulido M, Italiano A. Pembrolizumab combined with low-dose cyclophosphamide and intra-tumoral injection of the toll-like receptor 4 agonist G100 in patients with advanced pretreated soft tissue sarcoma: results from the PEMBROSARC basket study. J Hematol Oncol. 2022 Oct 27;15(1):157. doi: 10.1186/s13045-022-01377-2.
Derived from this study: PubMed 38374062Sun CM, Toulmonde M, Spalato-Ceruso M, Peyraud F, Bessede A, Kind M, Cousin S, Buy X, Palussiere J, Bougouin A, Sautes-Fridman C, Fridman HW, Pulido M, Italiano A. Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study. Mol Cancer. 2024 Feb 19;23(1):37. doi: 10.1186/s12943-024-01942-y.
Derived from this study: PubMed 31442817Le Cesne A, Marec-Berard P, Blay JY, Gaspar N, Bertucci F, Penel N, Bompas E, Cousin S, Toulmonde M, Bessede A, Fridman WH, Sautes-Fridman C, Kind M, Le Loarer F, Pulido M, Italiano A. Programmed cell death 1 (PD-1) targeting in patients with advanced osteosarcomas: results from the PEMBROSARC study. Eur J Cancer. 2019 Sep;119:151-157. doi: 10.1016/j.ejca.2019.07.018. Epub 2019 Aug 21.
Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
Individual participant dataSharing planned: No

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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.

Antoine ITALIANO, MD, PhD study chair

Institut Bergonié

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Combination of MK3475 with Metronomic CP and Combination of MK3475 with Metronomic CP and G100 in people with Sarcoma, run by Institut Bergonié at 8 sites in France.

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 28 inclusion and 19 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 10 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 10 Dec 2025). 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?

Percentage of Participants in Objective Response at 6 Months (time frame: 6 months from treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02406781, which also lists 6 linked publications.

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 10 Dec 2025.