University of Nebraska Medical Center, Omaha, NE
Kelsey Klute , Elizabeth Garrett-Mayer , Susan Halabi , Pam K. Mangat , Reza Nazemzadeh , Kathleen J Yost , Nicole L. Butler , Venu Perla , Richard L. Schilsky
Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with BRAF V600E mutation treated with C+V are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. Recommended dosing was C, 60 mg orally once daily for 21 days, 7 days off and V, 960 mg orally twice daily. Simon two-stage design was used to test the null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Thirty pts enrolled from August 2016 to August 2018; 2 were not evaluable for efficacy. Demographics and outcomes are summarized in Table. All pts had BRAF V600E mutations. Eight PR and 8 SD16+ were observed for DC and OR rates of 57% (90% CI, 43% to 67%) and 29% (95% CI, 13% to 49%), respectively. Twelve pts had at least 1 grade 3 AE or SAE at least possibly related to C+V including elevated liver enzymes, decreased lymphocytes, dyspnea, diarrhea, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper GI hemorrhage, and vomiting. Conclusions: The combination of C+V showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations. Further study is warranted to confirm the efficacy of C+V in this population. Clinical trial information: NCT02693535
Median age, yrs (range) | 62 (37, 77) | |
---|---|---|
Female, % | 63 | |
ECOG Performance Status, % | ||
0 | 23 | |
1 | 57 | |
2 | 20 | |
Prior systemic regimens, % | ||
1-2 | 37 | |
≥3 | 63 | |
DC rate, % (OR or SD16+) (90% CI)1 | 57 (43, 67) | |
OR rate, % (CR or PR) (95%)1 | 29 (13, 49) | |
Median PFS, wks (95% CI)1 | 15.8 (14.4, 18.1) | |
Median OS, wks (95% CI)1 | 38.9 (26.1, 49.4) | |
Tx-related AEs, SAEs (% pts) | ||
AEs, grade 3 | 33 | |
SAEs | 20 |
1N=28
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