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.
|