Table 1 Clinical trial agents targeting p53 negative regulators
From: Targeting mutant p53 for cancer therapy: direct and indirect strategies
ClinicalTrial.gov identifier and reference | Study design | Intervention and sample size (n) | Outcomes (n) | Toxicities (n) | Conclusions |
|---|---|---|---|---|---|
NCT02016729; Erba et al. [146] | Non-randomized phase 1, open label | AMG232 (26) AMG232 + trametinib (10) | MLFS (4) CR (1), PR (1) | AEs (25) AEs (10) | AMG232 is activate and tolerable |
NCT01164033, Patnaik et al. [147] | Randomized phase 1, open label | RG7112 single dose (23) RG7112 multiple dose (53) | N/A SD (6) | AEs (16), SAEs (2) AEs (52), SAEs (13) | High-dose consecutive is superior |
NCT00623870; Andreeff et al. [61] | Phase 1, open label | RG7112 for AML (96) RG7112 for CML (20) | CR (2), CRp (1), PR (1), MLFS (1), MTD (1500 mg BID), DLTs (3) PR (1), SD (15), MTD (N/A), DLTs (N/A) | AE grade ≥ 3 (86), AE grade ≥ 4 (34) | RG7112 is activated but need combination therapy |
Non-randomized phase 1, open label | RG7775 for AML (26) RG775 for solid tumor (41) | CR (2), PR (2), HI/SD (7), MTD (200 mg), DLTs (4) SD (17), MTD (110 mg), DLTs (5) | AEs (25), SAEs (22) AEs (40), SAEs (6), death (2) | No improvement of safety | |
NCT02264613; Saleh et al. [150] | Non-randomized phase 1/2, open label | ALRN-6924: 0.16–4.4 mg/kg (41) ALRN-6924: 0.32–2.7 mg/kg (41) | CR (1), PR (1), SD (12), DLTs (5) CR (1), PR (8), SD (8), DLTs (0) | SAEs (7) SAEs (1) | ALRN-6924 is activated and tolerable |
NCT01462175; Italiano et al. [151] | Non-randomized phase 1, open label | RG7388 QW*3 (36) RG7388 QD*3 (15) RG7388 QD*5 (34) | SD (10), MTD (1600 mg BID) SD (5), MTD (500 mg BID) SD (8), MTD (500 mg QD) | AEs (10), death (2) AEs (12) AEs (27), death (4) | RG7388 induces durable SD |
NCT01773408; Yee et al. [44] | Non-randomized phase 1, open label | Idasanutlin (46) Idasanutlin-C (76) | CRc (7) CRc (21) | AE grade ≥ 3 (31), SAEs (24), death (11) AE grade ≥ 3 (69), SAEs (48), death (16) | Idasanutlin is activated and safety |
NCT02545283; Papai et al. [152] | Non-randomized phase 1, open label | [13/14C]-label idasanutlin (8) | SD (1) | N/A | Hepatic impair alters idasanutlin exposure |
NCT01760525; Bauer et al. [153] | Non-randomized phase 1, open label | CGM097 400 mg QW*3 (31) CMG097 300–700 mg QW*3 (20) | PR (1), SD (10) SD (9) | AE grade ≥ 3 (25), AE grade ≥ 4 (12) | CMG097 is tolerable with partial efficacy |
NCT02143635; Jeay et al. [154] | Non-randomized phase 1, open label | HDM201 daily (20) HDM201 QW*3 (24) | N/A | N/A | Intermittent regimen is better |