Yuan Yuan, M.D., Ph.D., Medical Oncologist at the City of Hope discusses the SABCS 2020 abstract – Phase I study of ipatasertib with chemotherapy and atezolizumab in patients with metastatic triple-negative breast cancer.
BACKGROUND
One of the most common cancer drivers of breast cancer is the pathway PI3K3-ATK.
In patients(pts) with metastatic triple-negative breast cancers (mTNBCs), the AKT inhibitor ipatasertib (ipat) has shown great efficacy.
The preclinical PDX model demonstrated synergy in TNBC2 between carboplatin and ipat.
Synergies between atezolizumab and ipatasertib3 were demonstrated in previous clinical trials.
The current Phase I trial is intended to assess the protection and effectiveness of the following combinations of ipat:
Carboplatin + ipatasertib + paclitaxel
Ipatasertib + carboplatin
Capecitabine + atezolizumab + ipatasertib
DESIGN OF STATISTICS
The IQ 3+3 model4 is the Phase I-dose escalation part. The extension of each schedule to 14 patients for Arms A, B, and at least 12 patients for Arm C would be Step 1b-part.
For this Phase, I analysis, the estimated combined sample size and the extended cohort at the recommended phase 2 dose (RP2D) will be approximately 40 patients (> 99 percent likelihood, based on 800 simulations) for Arms A and B together, with an additional 24 patients for Arm C expected (see below).
The sample size for weapons A and B would be 28 patients if level 1 on both triplet schedule A and double schedule B has appropriate toxicity. The DLT rate can be calculated for Arm C, with a minimum of 12 patients (maximum of 19), with a SE of less than 14.4 percent.
Accrual: 40