KEY TAKEAWAYS
- The INVINCIBLE phase II trial aimed to assess the tumor microenvironment’s immune response in vivo after IT injections of INT230-6.
- Pts were randomly assigned to receive IT injections of INT230-6 or saline placebo before surgery.
- This study is the first to investigate the potential of IT INT230-6 as an immune priming therapy for traditional immune quiescent ER+ breast cancers.
Local cytotoxic therapies can help to activate the immune system and make breast cancers more responsive to immunotherapies. Researchers aimed to assess the tumor microenvironment’s immune response in vivo after intratumoral (IT) injections of INT230-6.
The study enrolled women with newly diagnosed, early-stage, intermediate, or high-grade ER+ T1-T2 invasive breast cancers awaiting surgery. Patients(pts) were randomly assigned (2:1) to receive IT injections of INT230-6 or a saline placebo before surgery. RNA profiling of pre- (baseline biopsy) and post-treatment (surgical resection) tumor samples was conducted using Ion AmpliSeq Transcriptome Human Gene Expression (Thermo Fisher Scientific). DNA sequencing was performed using a comprehensive genomic profiling panel (OCAPlus) consisting of 500 genes.
Pts who received INT230-6 showed the most significant tumor necrosis. Among the 60 pre-treatment biopsies analyzed with OCAPlus, the most frequently mutated genes were PIK3CA (38%), TP53 (23%), CDH1 (22%), and TBX3 (17%). Common copy number changes were observed in CCND1 (23%), FGFR1 (18%), and CDH1 (17%). Gene expression analysis revealed marked differences in gene expression between the baseline biopsy and surgical samples in pts treated with the drug. Pathway analysis highlighted the post-treatment samples’ up-regulation of genes associated with TCR signaling, macrophage markers, IL-18 signaling, and B cell receptor signaling.
This study is the first to investigate the potential of IT INT230-6 as an immune priming therapy for traditional immune quiescent ER+ breast cancers.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.573
Clinical Trial: https://clinicaltrials.gov/study/NCT04781725
Melanie Spears, Megan Hopkins, Kianoosh Keyhanian, Susan Robertson, Linda Liao, Vida Talebian, Arif Ali Awan, Gregory Russell Pond, John Bartlett, Lewis H. Bender, Ian B. Walters, Vanessa Lopez-Ozuna, and Angel Arnaout. DOI: 10.1200/JCO.2023.41.16_suppl.573 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 573-573.
