A Phase 1/1b, Open Label, Multiple Dose, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors

Trial ID # NCT02660034
Phase I/Ib
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Pamiparib
Alternate Drug Names PARP inhibitor BGB-290
Drugs in Trial Pamiparib, Tislelizumab
Eligible Participant

Advanced solid tumors

Patients Enrolled

230 [Dose escalation: 49, median 2 prior therapies (34 OvCa; 16 Pt-S, 18 Pt-R)]

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DCR, RP2D, evaluated per RECIST

Biomarkers

Exploratory: BRCA1/2

Efficacy

RP2D: tislelizumab 200mg IV Q3W+pamiparib 40 mg BID

ORR: 32% (2CR, 7PR, 2uPR, n=34)
DCR: 56% (2CR, 7PR, 2uPR, 8SD, n=34)
 
Exploratory analysis Pt status, BRCA status:
Pt-S (n=16): ORR: 44% (2CR, 4PR, 1uPR); DCR: 63% (2CR, 4PR, 1uPR, 3SD)
Pt-R (n=18): ORR: 22% (3PR, 1uPR); DCR: 50% (3PR, 1uPR, 5SD)
BRCA WT (n=24): ORR: 25% (2CR, 4PR)
BRCA MUT (n=7): ORR: 57% (2PR, 2uPR)
BRCA unk (n=3): ORR: 33% (1PR)

Clinically Significant Adverse Events

DLT: autoimmune hepatitis (Grade 4), rash (Grade 3), nausea (Grade 2), nausea and vomiting (Grade 2)
Serious AE: hepatitis or autoimmune hepatitis (4 patients)
Grade 3-4 AE: anemia (12%)

Conclusion

Pamiparib+tislelizumab is well tolerated and associated with antitumor responses

Reference

Friedlander et al. Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre,open-label, phase 1a/b trial. Lancet Oncol (2019) 20(9):1306-1315
https://www.ncbi.nlm.nih.gov/pubmed/31378459