Abstract
Talazoparib beyond BRCA: A phase II trial of talazoparib monotherapy in BRCA1 and BRCA2 wild-type patients with advanced HER2-negative breast cancer or other solid tumors with a mutation in homologous recombination (HR) pathway genes.
Author
person
Joshua James Gruber
Stanford University School of Medicine, Stanford, CA
info_outline
Joshua James Gruber, Anosheh Afghahi, Alyssa Hatton, Danika Scott, Alex McMillan, James M. Ford, Melinda L. Telli
Full text
Authors
person
Joshua James Gruber
Stanford University School of Medicine, Stanford, CA
info_outline
Joshua James Gruber, Anosheh Afghahi, Alyssa Hatton, Danika Scott, Alex McMillan, James M. Ford, Melinda L. Telli
Organizations
Stanford University School of Medicine, Stanford, CA, University of Colorado School of Medicine, Aurora, CO, Stanford University School of Medicine, Palo Alto, CA
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Other Foundation
Background:
Talazoparib, a PARP inhibitor, is active in germline
BRCA1/2
mutant advanced HER2-negative breast cancer, but its activity beyond
BRCA1/2
is unknown. We conducted a single institution phase II trial to evaluate talazoparib in patients (pts) with advanced HER2-negative breast cancer or other solid tumors with a germline (g) or somatic (s) alteration in HR pathway genes not including
BRCA1/2
.
Methods:
Eligible pts had measurable disease, lacked a germline or somatic mutation in
BRCA1/2
, received at least one prior therapy for advanced HER2-negative breast cancer or other solid tumor and had a HR pathway gene mutation:
PALB2, CHEK2, ATM, NBN, BARD1, BRIP1, RAD50, RAD51C, RAD51D, MRE11, ATR, PTEN, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL
. Pts with no progression on or within 8 weeks of their last platinum dose were eligible. Pts were treated with talazoparib 1 mg po daily until disease progression. Response was assessed every 8 +/- 1 weeks. If 2 or more responses were observed in 10 pts in stage I, the study would proceed to stage II and enroll 10 additional pts. The null hypothesis of a ≤ 5% objective response rate would be rejected if at least 3 of 20 respond.
Results:
Twenty pts were enrolled; 13 breast cancer (12 HR+/HER2-, 1 TNBC) and 7 non-breast cancer (pancreas, colon, uterine, testicular, parotid salivary). Median age was 54 years. Of 12 response evaluable pts with breast cancer, 3 had a RECIST response (ORR = 25%, 2 g
PALB2
, 1 g
CHEK2
/g
FANCA/sPTEN
) and 3 additional pts (g
PALB2
, s
ATR
, s
PTEN
) had SD ≥ 6 months (CBR = 50%). No responses were seen in non-breast tumors; 2 (g
CHEK2
testicular, g
ATM
colon) had SD ≥ 6 months. Talazoparib was well tolerated; 5 patients required dose reduction for hematologic toxicity. Results of tumor HR deficiency status assessment from metastatic biopsies and serial ctDNA profiling will be presented.
Conclusions:
In this proof-of-concept phase II study, single agent talazoparib demonstrated activity in HER2-negative advanced breast cancer pts with a HR pathway mutation beyond
BRCA1/2
. Further evaluation of talazoparib in this population is warranted. Clinical trial information:
NCT02401347