Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02406781 | Combination of MK3475 and Metronomic Cyclophosphamide in Patients With Advanced Sarcomas : Multicentre Phase II Trial | PHASE2 | COMPLETED | 129 | — | — | Jun 1, 2015 | Jan 15, 2023 | Dec 10, 2025 | 8 | France |
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
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| 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. |
| 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. |
Inclusion Criteria: 1. 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. 2. Advanced non resectable / metastatic disease for strata 1 to 6. For s...