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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-004568-39 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| Ministry of Health, France | OTHER_GOV |
| Immune Design, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | INDUSTRY |
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This is a multicenter study assessing the efficacy of different therapeutic strategy in patients with advanced sarcomas.
This is a phase 2 trial with 7 strata :
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combination of MK3475 with Metronomic CP | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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. | 6 months from treatment initiation |
| Measure | Description | Time Frame |
|---|---|---|
| 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). |
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Inclusion Criteria:
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.
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:
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).
Exclusion Criteria:
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.
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:
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| Name | Affiliation | Role |
|---|---|---|
| Antoine ITALIANO, MD, PhD | Institut Bergonié | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut Bergonié | Bordeaux | 33076 | France | |||
| Centre Oscar Lambret |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28662235 | Result | 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. | |
| 35618839 |
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8 centers:
Planned enrollment period : 72 months Treatment duration : 2-years maximum Follow-up : 12 months Duration of study : 7 years
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| ID | Title | Description |
|---|---|---|
| FG000 | Stratum 1: Advanced Leiomyosarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 7, 2021 | Sep 1, 2025 |
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| 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. |
|
| 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. |
|
| 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. |
|
|
|
| Combination of MK3475 with Metronomic CP and G100 | Drug | 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. |
|
|
| 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. | 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. | From start of treatment, and during treatment until death for any cause for up to 30 months |
| Lille |
| 59020 |
| France |
| Centre Léon Bérard | Lyon | 69373 | France |
| Institut Paoli Calmettes | Marseille | 13273 | France |
| Institut Curie | Paris | 75005 | France |
| Institut de Cancérologie de l'Ouest | Saint-Herblain | 44805 | France |
| Institut Claudius Regaud | Toulouse | 31052 | France |
| Institut Gustave Roussy | Villejuif | 94800 | France |
| 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. |
| 36303228 | Result | 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. |
| 38374062 | Derived | 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. |
| 31442817 | Derived | 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. |
| 31401903 | Derived | 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. |
| FG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| FG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| FG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| FG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| FG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| FG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously. Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Stratum 1: Advanced Leiomyosarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| BG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously . Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
| BG007 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Inter-Quartile Range | years |
| ||||||||||
| Sex: Female, Male | Count of Participants | Participants | No |
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| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| ||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Population eligible and assessable for the primary endpoint: eligible patients who received at least one administration of PEMBROLIZUMAB and one administration of Metronomic CP. | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months from treatment initiation |
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| Primary | 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. | Population eligible and assessable for the primary endpoint: eligible patients who received at least:
| Posted | Number | 95% Confidence Interval | percentage of participants | 6 months from treatment initiation |
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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). | Population eligible and assessable for the primary endpoint: eligible patients who received at least:
| Posted | Number | 95% Confidence Interval | percentage of participants | 6 months from treatment initiation |
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Population eligible and assessable for the primary endpoint: eligible patients who received at least:
| Posted | Median | 95% Confidence Interval | months | From start of treatment, and during treatment until progression or death for any cause, whichever occurs first, for up to 12 months. |
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Population eligible and assessable for the primary endpoint: eligible patients who received at least:
| Posted | Median | 95% Confidence Interval | months | From start of treatment, and during treatment until death for any cause for up to 30 months |
|
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.
Safety population: All patients with at least one treatment (any) administration.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Stratum 1: Advanced Leiomyosarcoma | 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. 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. | 13 | 15 | 5 | 15 | 15 | 15 |
| EG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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. | 14 | 16 | 10 | 16 | 16 | 16 |
| EG002 | Stratum 3: Advanced Other Sarcoma | 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. 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. | 7 | 16 | 9 | 16 | 16 | 16 |
| EG003 | Stratum 4: Advanced GIST | 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. 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. | 12 | 16 | 12 | 16 | 16 | 16 |
| EG004 | Stratum 5: Advanced Soft-tissue Sarcomas | Treatment strategy A: Combination of MK3475 with Metronomic CP administered to patients with advanced soft-tissue sarcomas. MK3475 will be administered intraveinously. Metronomic CP (Cyclophosphamide) will be adminstered orally. 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. | 3 | 10 | 9 | 10 | 10 | 10 |
| EG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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. | 15 | 35 | 14 | 35 | 35 | 35 |
| EG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously. Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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. | 9 | 19 | 8 | 19 | 19 | 19 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Cardiac disorders - Other, specify | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gastric perforation | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Rectal hemorrhage | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Death NOS | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| General disorders and administration site conditions | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Localized edema | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hepatic hemorrhage | Hepatobiliary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hepatobiliary disorders - Other, specify | Hepatobiliary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Portal vein thrombosis | Hepatobiliary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Allergic reaction | Immune system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Anorectal infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Bronchial infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Hepatic infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Spesis | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | CTCAE (4,0) | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| CPK increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Lymphocytes count decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Metabolism and nutrition disorders - Other, specif | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4,0) | Systematic Assessment |
| |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4,0) | Systematic Assessment |
| |
| Edema cerebral | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Nervous system disorders - Other, specify | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Adult respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Vaginal hemorrhage | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hematoma | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Blood and lymphatic system disorders - Other, specify | Blood and lymphatic system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Lymph node pain | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Atrial flutter | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Cardiac disorders - Other, specify | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Mitral valve disease | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hearing impaired | Ear and labyrinth disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Middle ear inflammation | Ear and labyrinth disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Endocrine disorders - Other, specify | Endocrine disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Conjonctivitis | Eye disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Watering eyes | Eye disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Bloating | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gastrointestinal disorders - Other, specify | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hemorrhoids | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Chill | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Edema limbs | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Fatigue | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Flu like symptoms | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Gait disturbance | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| General disorders and administration site conditions - Other, specify | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Localized edema | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Malaise | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pain | General disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hepatobiliary disorders - Other, specifiy | Hepatobiliary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Allergic reaction | Immune system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Anaphylaxis | Immune system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Autoimmune disorder | Immune system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Immune system disorders - Other, specify | Immune system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Bronchial infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Infections and infestations - Other, specify | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Lip infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Meningitis | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Rhinitis infective | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Upper respiratory infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Wound infection | Infections and infestations | CTCAE (4,0) | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | CTCAE (4,0) | Systematic Assessment |
| |
| Injury, poisoning and procedural complications - Other, specify | Injury, poisoning and procedural complications | CTCAE (4,0) | Systematic Assessment |
| |
| Postoperative hemorrhage | Injury, poisoning and procedural complications | CTCAE (4,0) | Systematic Assessment |
| |
| Vascular access complication | Injury, poisoning and procedural complications | CTCAE (4,0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Alkaline phosphatase increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| CPK increase | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| GGT increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Investigations - Other, specify | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Lipase increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Lymphocyte count increased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Weight loss | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE (4,0) | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hyperuricemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Metabolism and nutrition disorders - Other, specify | Metabolism and nutrition disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorder - Other, specify | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Neoplasms benign, malignant and unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4,0) | Systematic Assessment |
| |
| Tumor pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4,0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dysesthesia | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Nervous system disorders - Ohter, specify | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Paresthesia | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Phantom pain | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Confusion | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Libido decreased | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Psychiatric disorders - Other, specify | Psychiatric disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Acute kidney disease | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Cystitis noninfective | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hematuria | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary frequency | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Irregular menstruation | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Reproductive system and breast disorders - Other, specify | Reproductive system and breast disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Respiratory, thoracic and mediastinal disorders - Other, specify | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Sinus disorders | Respiratory, thoracic and mediastinal disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hyperrhidrosis | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Palmar-plantar erythrodysesthesia syndrome | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Rash acneiform | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Skin and subcutaneous tissue disorders - Other, specify | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hot flashes | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Lymphedema | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
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| Thromboembolic event | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
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| Vascular disorders - Other, specify | Vascular disorders | CTCAE (4,0) | Systematic Assessment |
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Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pr Antoine Italiano | Institut Bergonie | 0524071947 | a.italiano@bordeaux.unicancer.fr |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 17, 2015 | Oct 6, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D007890 | Leiomyosarcoma |
| D012516 | Osteosarcoma |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009379 | Neoplasms, Muscle Tissue |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
| D003520 | Cyclophosphamide |
| C000706812 | TLR4 agonist G100 |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
Not provided
Not provided
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| OG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously . Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
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| OG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously . Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
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| OG001 | Stratum 2: Advanced Undifferentiated Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously . Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
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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.
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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8.
A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation.
| OG002 | Stratum 3: Advanced Other Sarcoma | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG003 | Stratum 4: Advanced GIST | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG004 | Stratum 5: Advanced Soft-tissue Sarcomas | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG005 | Stratum 6: Advanced Soft-tissue Sarcomas With Immune Signature | 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. 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 (200mg in 30 minutes -5 min/+10 min) and given every 3 weeks on day 8. A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation. |
| OG006 | Stratum 7: Metastatic Soft-tissue Sarcoma. | Treatment strategy B: Combination of MK3475 with Metronomic CP and G100. MK3475 will be administered intravenously . Metronomic CP (Cyclophosphamide) will be administered orally. G100 will be administered by intra-tumoral injection. 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 intraveinously (200mg in 30 minutes -5 min/+10 min) 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. |
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