Enrico Martin

170 Chapter 7 Table 3 Ongoing clinical trials. NCT number Country Phase Tumor type N Age Drug Pathway Completion date Membrane targets NCT02584647 US I II STS MPNST 49 ≥18 Pexidartinib + sirolimus Multikinase, mTOR 10-2021 NCT02452554 US II CD56 expressing tumors (MPNST) 114 1-30 Lorvotuzumab mertansine CD56 03-2020 NCT02584309 US II STS (MPNST) 73 ≥18 Doxorubicin + olaratumab Anthracycline, PDGFRα 10-2023 NCT02180867 US II/III* STS (MPNST) 340 ≥2 Doxorubicin + ifosfomide +/-pazopanib Multikinase, anthracycline, alkylans 12-2018 Cytoplasmic targets NCT03433183 US II MPNST 21 ≥18 Vistusertib + selumetinib mTOR, MEK 09-2021 NCT02008877 US I/II MPNST 20 ≥16 Sirolimus + ganetespib mTOR, Hsp90 07-2018 NCT02601209 US I II STS STS (MPNST) 137 ≥18 Sapanisertib +/- pazopanib mTOR, multikinase 09-2020 Nuclear targets NCT02986919 US II MPNST 24 ≥18 CPI-0610 BET 03-2020 NCT03009201 US IB STS (MPNST) 36 ≥12 Ribociclib + doxorubicin CDK4/6, anthracycline 12-2020 Immunotherapy and oncolytic virus NCT02691026 Norway II MPNST 18 ≥18 Pembrolizumab PD1 12-2025 NCT02834013 US II Rare tumors (MPNST) 707 ≥18 Nivolumab + ipilimumab PD1, CTLA4 08-2020 NCT02700230 US I MPNST 30 ≥18 MV-NIS oMV 06-2021 NCT00931931 US I Non-CNS solid tumors (MPNST) 18 7-30 HSV1716 oHSV 03-2018 *: neoadjuvant in resectable disease BET: bromo- and extra-terminal domain, CDK: cyclin-dependent kinase, CNS: central nervous system, Hsp90: heat shock protein 90, M: months, MEK: mitogen-activated protein kinase kinase, MPNST: malignant peripheral nerve sheath tumor, mTOR: mammalian target of rapamycin, N: accrual of patients, oHSV: oncolytic herpes simplex virus, oMV: oncolytic measles virus, PD1: programmed cell death protein 1, PDGFRα: platelet-derived growth factor receptor alpha, STS: soft tissue sarcoma, US: United States Nuclear targets – trials Although in a preclinical setting alisertib showed positive results, a trial that included ten MPNST patients found no tumor response ( Table 2 ). 67 Median PFS was thirteen weeks, with a median OS of sixty-nine weeks. A trial that was ongoing at time of publication was investigating the effect of a bromo- and extra-terminal domain (BET) inhibitor in advanced or metastatic MPNST patients (NCT02986919, Table 3 ).An ongoing phase Ib trial enrolling patients with MPNSTs, among other soft tissue sarcomas, is investigating the effect of ribociclib, a CDK4/6 inhibitor, combined with doxorubicin (NCT03009201).