PD-L1 expression + HER-2 expression

Background Recent results from the KEYNOTE-811 study showed that first-line pembrolizumab was superior to placebo with respect to progression-free survival (PFS) in combination with trastuzumab and chemotherapy in patients with HER2 positive metastatic gastric cancer (GC). Conclusions The high proportion of CD4 Tregs, CD8 Tex and the elevated exhausted score in the subgroup with PD-L1 negative in HER2 positive GCs suggesting immune exclusive environment compared to HER2 and PD-L1 coexpressing group. Considering increased expression of immune checkpoint proteins other than PD-1/PD-L1, for patients with HER2-positive and PD-L1 negative, combination therapy with other immune checkpoint inhibitors rather than anti-PD-1/PD-L1 may be suggested.

CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.

While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

P1, N=9, Enrolling by invitation, Base Therapeutics (Shanghai) Co., Ltd.

Aberrant p53 in CCO is infrequent but associated with poor prognosis independent of stage. Presence of tumor budding could be a screening tool for p53 testing. High prevalence of HER2 and PD-L1 expression indicates the eligibility of patients with CCO for ongoing clinical trials using these therapeutic targets.

Discordance may be attributed to tissue heterogeneity. Substantial overlap between PD-L1 positivity and HER2 positivity supports combined administration of HER2-targeted agents and checkpoint inhibitors.

PD-L1 expression is upregulated in more than half of patients with GAC. Anti-PD-L1 treatment combined with anti-HER2 therapy may benefit patients with locally advanced GAC with HER2 overexpression.

As anticipated, the strength of HER2 expression and ER expression were the most significant predictors of favorable and unfavorable RCB response to neoadjuvant THP, respectively. This highly multiplexed protein expression analysis demonstrated significant differences between the immune microenvironment of HR+ and HR- HER2+ breast tumors, implying that distinct immunological targets should be explored in the treatment of HER2+ breast cancer according to HR status. Table 1: Differences between HR+/HER2+ and HR-/HER2+ patients *FDR p-value < 0.05 (otherwise, p-value < 0.05) Table 2: Predictors of RCB response *FDR p-value < 0.05 (otherwise, p-value < 0.05).HR-/HER2+ patients are not shown in Table 2 as only 2 HR- patients had unfavorable RCB response.

RC48-ADC in combination with toripalimab had a good tolerance and promising anti-tumor activity in pts with mUC . Further evaluation of safety and efficacy is ongoing.