Phase 1b study evaluating a triplet combination of ipatasertib (IPAT), atezolizumab (Atezo), and paclitaxel (PAC) or nab-PAC as first-line (1L) therapy for locally advanced/metastatic triple-negative breast cancer (aTNBC)

Purpose Randomized trials in aTNBC have demonstrated improved efficacy with addition of Atezo to 1L nab-PAC in patients (pts) with PD-L1+ tumors, and with addition of the AKT inhibitor IPAT to 1L PAC. We report first results from a multicenter phase 1b study (NCT03800836) evaluating a triplet of IPAT, Atezo, and PAC or nab-PAC.

Methods Eligible pts had unresectable aTNBC, ECOG-PS 0/1, and no prior systemic therapy for advanced disease. Pts were assigned to PAC 80 mg/m² (Arm A) or nab-PAC 100 mg/m² (B), both given on days 1, 8, & 15, in combination with oral IPAT 400 mg/day (days 1-21) and IV Atezo 840 mg (days 1&15). Cycles were repeated every 28 days until loss of clinical benefit or unacceptable toxicity. After establishing tolerability (n=6), each arm was expanded to 20 pts. The primary endpoint is objective response rate (ORR; RECIST v1.1).

Results We report preliminary efficacy/safety data for the first 26 pts (18 PAC, 8 nab-PAC). Median follow-up was 6.1 months. Confirmed responses were seen in 19/26 patients (ORR 73 %), irrespective of PD-L1 status (82 % PD-L1+, 75 % PD-L1-, 57 % PD-L1 unknown) or PIK3CA/AKT1/PTEN alteration status (71 % Dx+, 82 % Dx-; 63 % Dx unknown). Treatment was generally tolerable. Grade ≥3 AE occurred in 54 %. The most common AE were diarrhea (88 %; grade ≥3 19 %) and rash (69 %; grade 3 27 %, no grade >3).

Conclusions The triplet regimen shows promising antitumor activity (73 % ORR), irrespective of biomarker status, and has manageable toxicity. This triplet regimen warrants further investigation.

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Artikel online veröffentlicht:
24. Juni 2020