This is Zhijie Wang from the Chinese Academy of Medical Sciences at Peking Uni Medical College. On behalf of Dr. Wang, it is my pleasure to present the updated biomarker analysis of Rational 307, a phase 3 study of T-selizomib plus chemotherapy versus chemotherapy alone for first-line advanced squamous non-small cell lung cancer. This is the order list. I have no financial relationships to disclose. The Rational 307 study demonstrated a significantly prolonged PFS with T-selizomib plus chemotherapy versus chemotherapy alone as first-line treatment for patients with advanced squamous non-small cell lung cancer. Here, I will present an exploratory analysis that evaluated the association of the established biomarkers with PFS benefit, including PD-L1 expression, tumor mutation burden from tissue and blood, as well as tumor inflammation signature, TIS. In this analysis, the two T-selizomib-containing regimens were combined into a single T-selizomib plus chemoarm, and compared with the chemoarm, baseline tumor tissue and blood samples were collected for the assessment of PD-L1, TMV, and the gene expression profiling. As a 1% cutoff, both PD-L1 positive and negative patients showed the PFS benefit of T-selizomib plus chemo versus chemo alone. Evaluation of PD-L1 cutoff to 25% or 50% did not differentiate PFS benefit of T-selizomib plus chemo versus chemo alone. The treatment biomarker interaction values were not significant. Therefore, in squamous non-small cell lung cancer, PFS benefit of T-selizomib plus chemo versus chemo were in respective of PD-L1 expression. Next, we examined the relationship between PFS and the tissue TMV, and found that T-TMV did not differentiate PFS benefit of T-selizomib plus chemo versus chemo alone at 10 mutations per megabase or higher cutoffs. Similar results were observed in the blood TMV dataset. The PFS benefit of T-selizomib plus chemo versus chemo alone was observed in both B-TMV high and low subgroups across different cutoff levels. We subsequently explored the gene expression profiling date and found an extensive array of interferon-related genes that were significantly associated with PFS benefit. This observation led us to further evaluate the tumor inflammation signature score. With a median cutoff, T-selizomib plus chemo demonstrated a significantly longer PFS than chemo alone in the T-high subgroup. The hazard ratio was 0.27. The treatment-specific effect was confirmed by interaction analysis. Note that for the T-low subgroup, although a larger hazard ratio was observed, the addition of T-selizomib to chemotherapy demonstrated a median PFS of 7.5 months as compared to 5.8 months with chemo alone. In conclusion, T-selizomib plus chemotherapy demonstrated PFS benefits versus chemotherapy alone, regardless of PDA1 expression, blood TMV, and tissue TMV status. This score was significantly associated with PFS benefit of T-selizomib plus chemotherapy versus chemotherapy alone, indicating the importance of tumor microenvironment in relation to the clinical benefit of combination treatment. The full presentation can be found at the joint RASLC-CAALC Cisco section on the virtual platform. Thank you.

Zhijie Wang

biomarker analysis

Rational 307

T-selizomib

chemotherapy