PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246

Trial ID # NCT02098343
Phase II
Drug Class Cell Cycle Inhibitors: p53
Drug Name APR-246
Alternate Drug Names PRIMA-1MET, p53 activator APR-246, PRIMA-1 analogue APR-246
Drugs in Trial APR-246, Carboplatin, Liposomal doxorubicin
Eligible Participant

TP53-mutated HGS ovarian cancer with disease progression 6-24 months after a first or second Pt-based therapy

Patients Enrolled

200 (Phase Ib: 28)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DCR, PFS, evaluated per RECIST

Biomarkers

TP53 MUT

Efficacy

ORR: 62% (3CR, 10PR, n=21)
DCR: 100% (3CR, 10PR, 8SD, n=21)
PFS: 10.5 months

Exploratory analysis Pt status:
Pt-S: ORR: 71% (2CR, 3PR, n=7)
Part Pt-S: ORR: 57% (1CR, 7PR, n=14)

Clinically Significant Adverse Events

Serious AE: 1 ruptured diverticulum
Grade 3-4 AE: any (75%), neutropenia (50%), infections (36%), anemia (25%), device related infection (25%), gastrointestinal disorders (18%), thrombocytopenia (14%), vomiting (11%)

Conclusion

Encouraging activity in TP53-mutated platinum-sensitive and partially platinum-sensitive patients

Reference

Gourley C et al. PISARRO: A EUTROC phase 1b study of APR-246 in combination with carboplatin (C) and pegylated liposomal doxorubicin (PLD) in platinum sensitive relapsed high grade serous ovarian cancer (HGSOC). J Clin Oncol (2016) 34:(suppl; abstr 5571)
https://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.5571

Basu B et al. PISARRO: A EUTROC phase 1b study of APR-246 with carboplatin (C) and pegylated liposomal doxorubicin (PLD) in relapsed platinum-sensitive high grade serous ovarian cancer. Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
https://oncologypro.esmo.org/Meeting-Resources/ESMO-2016/PISARRO-A-EUTROC-phase-1b-study-of-APR-246-with-carboplatin-C-and-pegylated-liposomal-doxo