Atezolizumab/Ipatasertib Demonstrates Potential in Solid Tumors

Andrea Botticelli, MD

Assistant Professor

Sapienza University

Coordinator

Breast Unit

Umberto I University Hospital

Rome, Italy

Atezolizumab (Tecentriq) with ipatasertib (GDC-0068) showed promising signs of extending survival with improved progression-free survival (PFS), overall survival (OS), and disease control rates (DCRs) in patients with advanced or metastatic solid tumors with PIK3CA, AKT, and PTEN alterations. Data from the phase 2 ROME trial were presented by Andrea Botticelli, MD, during the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies Congress 2025.

“The exploratory analysis of the ROME trial identified a group of patients with very poor prognosis cancer, who may benefit from targeted therapy with atezolizumab plus ipatasertib,” Botticelli, an assistant professor at Sapienza University of Rome and the coordinator of the Breast Unit at Umberto I University Hospital in Rome, Italy, said during a presentation of the data.

In the multibasket ROME trial (NCT04591431), patients with advanced or metastatic solid tumors who had received at least 1 and no more than 2 prior lines of histology-based therapy were enrolled. They were then randomly assigned 1:1 to receive either targeted therapy (TT) based on their mutation status or the standard of care (SOC) chosen by the investigator in the treatment part of the trial. Upon progression of disease, in the crossover part of the trial, patients received the opposite treatment of what they received in the treatment part (either TT or SOC).

The trial included 46 oncological centers. A total of 1794 patients, from November 2020 to August 2023, were screened, and of these, 897 patients were evaluated in the molecular tumor board (MTB) discussion. After the MTB decision, a total of 400 patients were randomly assigned to various TTs according to their mutation status. A group of 24 patients with PIK3CA, AKT, and PTEN alterations receiving atezolizumab plus ipatasertib were highlighted in this presentation.

In this group, there were 22 patients with primary central nervous system (CNS) tumors, 1 with ovarian cancer, and 1 with prostate cancer. Twelve patients received atezolizumab plus ipatasertib, and the other 12 received SOC. Overall, no patients achieved a complete or partial response; however, 3 patients (25%) in the TT arm and 1 patient (8.3%) in the SOC arm achieved stable disease. In those with CNS tumors, 2 patients (18.2%) and 1 patient (9.1%), respectively, achieved stable disease. Overall, the DCR was 25% in the TT arm and 8.3% in the SOC arm, and for those with CNS tumors the DCR was 18.3% and 9.1%, respectively.

Regarding PFS in all patients, the median PFS was 3.1 months (95% CI, 1.88-10.10) in the TT arm and 2.7 months (95% CI, 1.97-3.49) in the SOC arm. The HR was 0.54 (95% CI, 0.21-1.38). At 9 months, the PFS rate was 27.5% in the TT arm and 0% in the SOC arm. For those with CNS tumors, the median PFS was 5.2 months in the TT arm and 3.2 months in the SOC arm, and the HR was 0.56 (95% CI, 0.21-1.21). At 9 months, the PFS rate was 30% and 0%, respectively.

The median OS rate in all patients with PIK3CA, AKT, and PTEN alterations was 8.1 months (95% CI, 7.11-12.14) for those in the TT arm and 7.2 months (95% CI, 3.98-8.45) in the SOC arm. At 9 months the OS rate was 45.5% and 11.3%, respectively, and at 12 months it was 24.2% and 0%, respectively. The HR was 0.47 (95% CI, 0.17-1.29). For those with CNS tumors, the median OS was 9.6 months in the TT arm and 5.2 months in the SOC arm, with an HR of 0.42 (95% CI, 0.14-1.24). The 9-month OS rate was 50% and 13%, respectively, and the 12-month OS rate was 26.7% and 0%, respectively.

The global overall response rate (ORR) in all 400 patients was 13.3%, and in the population receiving TT it was 17.1% and 9.5% for those receiving SOC. The overall median PFS was 3.7 months (95% CI, 3.0-4.8) in the TT arm and 2.8 months (95% CI, 2.5-3.0) in the SOC arm. The HR was 0.64 (95% CI, 0.51-0.80; P = .0001). The 9-month overall PFS rate was 28.4% in the TT arm and 12.8% in the SOC arm, and the 12-month overall PFS rate was 22.3% and 7.7%, respectively.

The primary end point of the trial was ORR, and secondary end points included PFS, time to treatment failure, time to next treatment, safety, and OS. According to investigators, data for patients with no record of death were censored at the last date they were known to be alive.

“We performed comprehensive genomic profiling on both tissue and liquid biopsy, and once molecular alteration could be potentially targeted with a drug available, the clinical case was reviewed and discussed in the molecular tumor board,” Botticelli said regarding the review process for the trial.

PTEN was the most frequently altered gene within the pathway, with 12 deletions and 11 mutations (4 patients had both). PIK3CA was the second most altered gene in the pathway, with 5 mutations (2 patients also had PTEN alterations).

Outside the pathway, the most altered genes were TERT (16 patients, 67%), CDKN2A (14 patients, 58%), and EGFR (13 patients, 54%).

The study categorized gene alterations into several types, including amplification, deletion, mutation, rearrangements, and signatures, and mapped their distribution across various oncogenic pathways such as ALK/ROS1, ERBB2, FGFR, and others. Based on the specific gene alterations identified, patients were assigned targeted therapies. For instance, ALK/ROS1 alterations were treated with alectinib (Alecensa) and entrectinib (Rozlytrek), and FGFR alterations were addressed with pemigatinib (Pemazyre). However, many other treatments were included.

REFERENCE:

Botticelli A. Atezolizumab plus ipatasertib shows promise in extending survival for patients with PI3K/AKT/PTEN-altered advanced solid tumors: an exploratory analysis of the ROME trial. Ann Oncol. 2025;10(suppl 2):1-9. doi:10.1016/esmoop/ esmoop104255