Clinical trial Drugs Patient group Outcome measures Common / significant grade 3 or 4 toxicity (>10%)
Multi-targeted TKIs Multi-targeted TKIs Multi-targeted TKIs Multi-targeted TKIs Multi-targeted TKIs Multi-targeted TKIs
Italiano et al, 2020.140 CABONE-multicenter, single arm, phase 2 Cabozantinib Advanced ES (n=39) and OS (n=42), ≥12yo ORR 26% in ES, median PFS 4.4 mo, ORR 12% in OS with 33% PFS at 6 mo Hypophosphataemia, raised AST, palmar-plantar syndrome, pneumothorax, neutropenia
Duffaud et al, 2019.137 REGOBONE- double blind, placebo-controlled, phase 2 Regorafenib Progressive pretreated OS, n=43, ≥10yo Median PFS 16.4w (regorafenib) vs 4.1w (placebo) Hypertension, hand-foot skin reaction, fatigue, hypophosphataemia, chest pain
Duffaud et al, 2020.139
REGOBONE- double blind, placebo-controlled, phase 2
Regorafenib
Metastatic relapsed pretreated ES, n=41, ≥10yo
ORR 22% (5/23), median PFS- 11.4w (regorafenib) vs 3.9w (placebo)
Diarrhoea, hand-foot skin reaction
Davis et al, 2019.136 SARC024- randomized, double blind, phase 2 Regorafenib Advanced/ metastatic pretreated OS, n=42, 18-76yo Median PFS- 3.6mo and 1.7mo with regorafenib vs placebo, P.017 Hypertension
Xie et al, 2019.141 Single arm, phase 2 Apatinib Relapsed/ unresectable OS, n=37, ≥16yo ORR 43%, 4mo PFS 57% Pneumothorax, wound dehiscence
Gaspar et al.165 Single arm, phase 1/2 Lenvatinib single agent Relapsed OS, n=31, 2 to ≤25yo ORR 6.9%, 4mo PFS 32% Headache, diarrhoea, vomiting, decreased appetite, proteinuria, hypothyroidism, hypertension, pyrexia, weight loss
Gaspar et al.142
Single arm, phase 2
Lenvatinib + etoposide + ifosfamide in phase 2 expansion cohort
Relapsed/ refractory OS, n=22 (8 evaluable patients in phase 2), 2 to ≤25yo
Phase 1 dose finding cohort: ORR 12.5%, 4mo PFS in 12/18 (68%) Phase 2 cohort: 4mo PFS in 5/8 (62%)
Pneumothorax, haematologic toxicity
PARP inhibitors PARP inhibitors PARP inhibitors PARP inhibitors PARP inhibitors PARP inhibitors
Choy et al, 2014.144
Single arm, prospective phase 2
Olaparib
Metastatic/ recurrent ES, n=12, 18-70yo
Median PFS 5.7w, SD in 4/12
Haematologic, pain
Chugh et al, 2020.146
SARC025- multicenter, phase 1
Niraparib + temozolomide (Arm 1) or irinotecan (Arm 2)
Advanced ES, n=29, ≥13yo
Median PFS in Arm 1: 9w and in Arm 2: 16w Arm 1: ORR 0/17 Arm 2: ORR 8%- 1/12 PR and 6 SD
Arm 1- DLT: Haematologic, Arm 2- DLT: gastrointestinal toxicity, elevated ALT
Schafer et al, 2019.145 Single arm, phase 1/2 Talazoparib plus temozolomide Recurrent/ refractory solid tumors, n=40, 4-25yo ES- 2/10 prolonged SD (8 cycles) DLTs: haematologic
Federico et al, 2020.166 Single arm, phase 1 Talazoparib + irinotecan (A) plus temozolomide (B) Recurrent/ refractory solid tumors (50% ES), n=41, median age 14.6yo ORR 10% (A), ORR 25% (B) Febrile neutropenia, diarrhoea
EWSR1-FLI1 target agents EWSR1-FLI1 target agents EWSR1-FLI1 target agents EWSR1-FLI1 target agents EWSR1-FLI1 target agents EWSR1-FLI1 target agents
Ludwig et al, 2021.160
TK216-01, phase 2 dose (RP2D)
TK216± vincristine
Relapsed/ refractory metastatic ES, mean age 31yo A. Schedule escalation cohort, n=32 B. 14-day infusion 200mg/m2/d (RP2D) expansion cohort, n=35 CR 7%, SD 39%, PD 54%, SD median duration 113 days (B) 3 patient tumor responses
Most common: haematologic toxicity, fatigue.