Preliminary antitumour activity
adenocarcinoma of the breast, SD, tumour
DISEASE, METASTATIC PROSTATE CANCER, TUMOUR, BEST
Best overall response is shown in Table Best overall response (evaluable-for-efficacy analysis set).Two cycles defined as 56 days in 28-day cycles; 42 days in 21-day cycles.Notably, the patient in Cohort 6 with a PR had an 80% reduction from baseline in sum of target lesion diameters. The first two scans showed SD, then a PR was observed at the third scan. He remained on treatment for a further 40 weeks and then discontinued. He had previously received 3 treatment regimens for metastatic prostate cancer (bicalutamide, leuprolide acetate, and abiraterone acetate), and had a best overall response of SD prior to progression on all 3 regimens with a rapid rise of prostate-specific antigen reported with the bicalutamide regimen. A tissue sample from this patient showed three distinct AR mutations, a BRCA2-ERG rearrangement and a TMPRSS2 rearrangement; plasma samples showed mutations in ARID1A, MET, RB1, AR and CDKN2A. Germline testing showed a BRCA2 deletion/duplication. Additionally of note, 1 patient with cancer of pancreaticobiliary origin in Cohort 8 had SD for 66 weeks; this patient had a best overall response of PR or non-CR/non-PD before progression on 3 prior treatment regimens (FOLFIRINOX [folinic acid, fluorouracil, irinotecan, and oxaliplatin], capecitabine, and paclitaxel plus gemcitabine followed by gemcitabine). Another patient with adenocarcinoma of the breast in Cohort 7 had the longest duration of therapy of >17 months, and a best overall response of SD. The patient had oestrogen receptor-positive, progesterone receptor-positive disease, and HER2 non-amplified status by dual in situ hybridisation. Immunohistochemistry staining showed the tumour was positive for AE1/3, CK7, GATA-3 and GCDFP-15; and was negative for CK20, PAX-8, CDX-2, WT-1, TTF-1, mammaglobin and BRAF V600E. Genomic profiling showed a TP53 R723H mutation.