Assay Predicts Response to Neoadjuvant Atezolizumab Plus Chemotherapy in TNBC

The DetermaIO gene expression test identified patients with early-stage triple-negative breast cancer (TNBC) who benefitted from neoadjuvant atezolizumab (Tecentriq) plus carboplatin and nab-paclitaxel (Abraxane) resulting in improved pathologic complete response (pCR), according to data from the phase 2 NeoTRIP trial (NCT002620280).^1,2

Findings announced by Oncocyte and published in Clinical Cancer Research showed that among patients treated with atezolizumab plus chemotherapy, those who tested IO-positive per the DetermaIO assay (n = 43) experienced a pCR rate of 69.8% compared with 44.6% for those who tested IO-negative (n = 65; P = .011). Among patients treated with chemotherapy alone, the pCR rates were 46.9% for the IO-positive population and 49.2% for the IO-negative population (P = .812).² The interaction test between DetermaIO and the treatment was found to be statistically significant (P = .043).

“We are thankful for the support from Matteo Dugo, PhD, and his team, and are thrilled that the data in this clinical trial and this publication clearly demonstrate that DetermaIO can identify patients who are more likely to benefit from immunotherapy,” Josh Riggs, chief executive officer of Oncocyte, stated in a news release.¹ “DetermaIO continues to outperform standard of care biomarkers and assays. A 69.8% pCR in the [experimental] treatment arm for IO-positive patients is fantastic and consistent with previous studies. We will add this study to our submission to Centers for Medicare and Medicaid Services [CMS] and continue our push for CMS reimbursement coverage so that we can broaden access to this valuable test.”

The multicenter, open-label NeoTRIP study enrolled 280 patients with stage II/III TNBC who were randomly assigned to received neoadjuvant carboplatin at area under the curve 2 plus nab-paclitaxel at 125 mg/m² on days 1 and 8 of every 3-week cycle for up to 8 cycles (n = 142); or the same chemotherapy regimen in combination with atezolizumab at 1200 mg on day 1 of each 3-week cycle for up to 8 cycles (n = 138).² Patients then underwent surgery, and up to 4 cycles of investigator’s choice of anthracycline-based chemotherapy were permitted in the adjuvant setting.

Additionally, 242 of 258 patients (93.8%) in the study’s per-protocol population underwent RNA sequencing data derived from pretreatment core biopsies. Furthermore, 85.3% of patients who underwent RNA sequencing also underwent DetermaIO RT-qPCR tests.

“Fragments per kilobase million values for both the 101-gene TNBC subtypes and the 27-gene DetermaIO signature were used to generate TNBC subtypes and the DetermaIO scores,” Dugo, the lead study author and a member of the Department of Medical Oncology at IRCCS Ospedale San Raffaele in Milan, Italy, and colleagues wrote in the publication of the data.

The RT-qPCR DetermaIO assay identified 58.2% of patients as IO-negative; this rate was 57% based on RNA-sequenced IO score. Based on the DetermaIO assay, 40% of patients in the atezolizumab arm and 44% of patients in the chemotherapy-alone arm were IO-positive.

Additional data showed that a significant positive association was observed between IO-positive status and PD-L1 status and stromal tumor-infiltrating lymphocytes (sTILs). Among IO-positive patients in both arms, 90.2% were PD-L1 positive, and 69.2% had sTILs in the highest tertile; these respective rates were 37.5% and 11.8% in patients who were IO negative.

When accounting for patients treated in both arms, there was no significant association between DetermaIO status and pCR rate. The overall pCR rates were 57.6% for IO-positive patients and 46.9% for IO-negative patients.

“We demonstrated that the 27-gene DetermaIO assay can identify the subset of TNBC that experienced improvement in pCR rate when atezolizumab was added to neoadjuvant chemotherapy,” study authors concluded. “[Patients with] IO-negative cancers had a similar pCR rate with or without atezolizumab…Based on these results, a prospective study or registry could be designed to directly test the clinical utility of the assay.”

References

1. Oncocyte’s DetermaIO Immuno-Oncology assay predicts response to atezolizumab in phase 2 clinical trial. News release. Oncocyte. October 8, 2024. Accessed October 11, 2024. https://investors.oncocyte.com/news-releases/2024/10-08-2024-133059653
2. Dugo M, Huang CS, Egle D, et al. The immune-related 27-gene signature DetermaIO predicts response to neoadjuvant atezolizumab plus chemotherapy in triple-negative breast cancer. Clin Cancer Res. Published online September 23, 2024. doi:10.1158/1078-0432.CCR-24-0149