Background: Ipatasertib (ipat) is an AKT inhibitor which has shown efficacy in combination with paclitaxel and atezolizumab in patients with triple negative breast cancer (TNBC). In previous trials, ipat was given 21 days on 7 days off due to gastrointestinal toxicities. The current trial was designed to test the safety and efficacy of ipat continuous dosing in combination with carboplatin (carbo) or carboplatin/paclitaxel (carbo/taxol). The trial was later amended to include an additional arm using ipat 21 days on 7 days off with capecitabine/atezolizumab (cape/atezo) to explore the safety of the combination. Methods: Patients with metastatic TNBC and up to 2 lines of prior chemotherapy were enrolled to receive the following: Arm A, ipat 400 mg daily, carbo AUC 2 and taxol 80 mg/m2 IV days 1, 8, 15, every 28 days; Arm B, ipat 400 mg daily, carbo AUC 2 IV days 1, 8, 15, every 28 days; Arm C, ipat 300 mg daily 21 days on 7 days off, cape 750 mg/m² 7 days on 7 days off, atezo 840 mg IV every 28 days. Ipat continuous dosing was used for Arms A and B. Ipat 21 days on 7 days off dosing was used for Arm C. The primary endpoint is safety and recommended phase II dose (RP2D). Secondary endpoints are response rate (RR) and overall survival (OS). Results: Twenty-three patients with median age 49 (29-75) were enrolled from 04/2019 to 12/2020, with 9 in Arm A, 10 in Arm B, and 4 in Arm C. A total of 15/23 (65%) had dose delay and 10/23 (43%) had dose modification. 3/4 (75%) of patients in Arm A had dose limiting toxicities (DLT) including diarrhea and gastric pain, which led to de-escalation to dose -1 with ipat (300 mg daily). 5 more patients were treated at dose -1 of Arm A with only 1 DLT (maculo-papular rash). No DLTs were observed in Arm B. Of the 4 patients treated in Arm C, 1 had DLT (maculo-papular rash). The RP2D for Arms A and B are: ipat 300 mg/carbo AUC2/taxol 80 mg/m2; ipat 400 mg/carbo AUC2. RP2D for Arm C has not been determined and accrual is ongoing. There were no clinically significant G4 toxicities in Arm A; G3 toxicities included 4/9 (44%) diarrhea, 1/9 (11%) hypertension, 1/9 (11%) stomach pain, and 1/9 (11%) neutropenia. For Arm B, G3 toxicities included 2/10 (20%) diarrhea, 1/10 (10%) anemia, 1/10 (10%) maculo-papular rash, and 1/10 (10%) hyperglycemia. For Arm C, there was 1/4 (25%) G3 maculo-papular rash. Best overall responses for Arm A were: 2/9 (22%) PR, 4/9 (44%) SD, and 3/9 (33%) PD. Best responses for Arm B were 2/10 (20%) PR, 6/10 (60%) SD, and 2/10 (20%) PD. For Arm C, best responses were 3/4 (75%) SD, and 1 not evaluable (repeat biopsy showed HER2+ disease). With a median follow up of 8.1 months, the median PFS was 4.0 months (95% CI [2.6, 5.3]). Conclusions: Continuous dosing of ipatasertib in combination with carbo or carbo/taxol is well-tolerated with modest efficacy. Clinical trial information: NCT03853707.