Abstract 224P
Background
Tenalisib (RP6530), a PI3K δ/γ and SIK3 inhibitor has demonstrated encouraging activity in T-cell lymphoma. Tenalisib’s major metabolite (IN0385) shows potent SIK3 inhibition. Preclinical studies in breast cancer cell lines have demonstrated that tenalisib potentiates the activity of taxol and doxorubicin. Tenalisib potentiated the activity of fulvestrant by inhibiting cell growth and causing cell cycle arrest in both MCF-7 and ZR.75.1 breast cancer cell lines.
Methods
A randomized, open-label study was designed to evaluate 2 doses (800 mg BID and 1200 mg BID) of tenalisib in HR+/HER2- locally advanced or MBC patients (pts) whose disease had progressed following at least one line of therapy. Tenalisib was given orally in a 28-days cycle until disease progression. Forty pts (20 pts at each dose level) were enrolled with the primary outcome being the percentage of pts without disease progression at the end of 6 months. ORR, PFS, and CBR were secondary outcomes.
Results
Enrolled pts had less than 2 lines of prior therapy in a metastatic setting; of these, 83% pts received prior endocrine therapy. Eleven (27.5%) out of 40 pts had de novo metastasis at primary presentation. Fourteen (35%) patients had primary resistance to endocrine therapy. As of 27-Apr 2022, of the 40 patients, 5 pts (12.5%) had PR and 22 (55%) had SD with a DCR rate of 67.5%. The median duration of treatment was 3.87months and ranged from 0.93 to 6.23+ months. Twenty-four (60 %) patients continue to be in the study of which 17 pts (43%) have completed 5 cycles of treatment. The most common AEs (≥10%) of any grade were transaminitis, GGT elevation, and rash. Grade 3/ 4 events were limited to GGT elevation (12.5%), transaminitis (12.5%). Discontinuations due to related AEs were infrequent (<5%) and limited to two events (one rash and one GGT elevation).
Conclusions
Tenalisib was well tolerated and showed a manageable safety profile at both dose levels. Based on the data from the ongoing study, overall efficacy response as a single agent in both primary and secondary resistant MBC continues to be encouraging and supports further development in MBC. Updated efficacy and tolerability data will be presented at the conference.
Clinical trial identification
NCT05021900.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Rhizen Pharmaceuticals AG.
Disclosure
All authors have declared no conflicts of interest.