TEST:

VENTANA PD-L1 (SP263) Assay

Chugai Pharmaceutical...announced that it obtained regulatory approval for an additional indication of the anti-cancer agent/humanized anti-PD-L1 monoclonal antibody Tecentriq® Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)] for the adjuvant treatment of PD-L1-positive non-small cell lung cancer (NSCLC) from the Ministry of Health, Labour and Welfare....VENTANA OptiView PD-L1 (SP263), a pathological testing kit marketed by Roche Diagnostics K.K., should be used to detect PD-L1 expression.

...Food and Drug Administration approved atezolizumab (Tecentriq, Genentech, Inc.) for adjuvant treatment following resection and platinum-based chemotherapy in patients with stage II to IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-approved test.

Of 546 PD-L1+ patients enrolled...TIS+ICC showed statistically significant and clinically meaningful OS improvement vs P+ICC (HR 0.74 [95% CI: 0.59-0.94], mOS 17.2 vs 12.6 mo; 1-sided P= .0056). Compared with P+ICC, TIS+ICC also had longer PFS (mPFS 7.2 vs 5.9 mo; HR 0.67 [95% CI: 0.55-0.83]), higher ORR (50.4% vs 43.0%), and more durable response (mDoR 9.0 vs 7.1 mo)....In RATIONALE 305, TIS+ICC provided significant and clinically meaningful improvement in OS vs P+ICC with well acceptable safety as 1L in PD-L1+ patients with advanced GC/GEJC.

TIS+ICC showed statistically significant and clinically meaningful OS improvement vs P+ICC (HR 0.74 [95% CI: 0.59-0.94], mOS 17.2 vs 12.6 mo; 1-sided P= .0056). Compared with P+ICC, TIS+ICC also had longer PFS (mPFS 7.2 vs 5.9 mo; HR 0.67 [95% CI: 0.55-0.83]), higher ORR (50.4% vs 43.0%), and more durable response (mDoR 9.0 vs 7.1 mo)....In RATIONALE 305, TIS+ICC provided significant and clinically meaningful improvement in OS vs P+ICC with well acceptable safety as 1L in PD-L1+ patients with advanced GC/GEJC.

700 pts were randomized (350 per arm); 358 (51.1%) had PD-L1+ tumors. With extended follow-up (median, ≥38 months in both arms for all pts; data cutoff, June 4, 2021), OS remained significantly longer in the avelumab+BSC vs BSC alone arm in all randomized pts and in pts with PD-L1+ tumors (Table).

Patients with both high PD-L1 expression and high TMB showed a good response to ICIs with the response rate of 64% and median progression-free survival of 9.0 months despite of small population.

Of these, 157 pts (tisle [n=89], ICC [n=68]) had vCPS ≥10% (PD-L1+ population)...The study met its primary endpoint: tisle clinically and significantly improved OS vs ICC in the ITT population (median OS: 8.6 vs 6.3 m; HR 0.70, 95% CI 0.57-0.85, p=0.0001). Tisle also demonstrated significant improvement in OS vs ICC in the PD-L1+ population...Tisle demonstrated statistically significant and clinically meaningful improvement in OS vs ICC in pts with advanced or metastatic ESCC who had disease progression during or after first-line systemic therapy.

An OS benefit was seen for avelumab 1L maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab 1L maintenance as a standard of care for pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy.

...1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive...R/M-NSCLC treated with pembrolizumab or nivolumab...In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

...1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive...R/M-NSCLC treated with pembrolizumab or nivolumab...In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

Avelumab + BSC significantly prolonged OS vs BSC alone in all randomized patients...Avelumab + BSC also significantly prolonged OS vs BSC alone in patients with PD-L1+ tumors....JAVELIN Bladder 100 met its primary objective, demonstrating significantly prolonged OS with 1L maintenance avelumab + BSC vs BSC alone in advanced UC in all randomized patients and patients with PD-L1+ tumors.

Stepwise OS and PFS improvement, favouring atezo, was seen up to bTMB ≥ 16; no further benefit was seen at ≥ 20.

Among the patients with PD-L1–positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib...

NSCLC patients with more higher PDL1 expression (PD-L1 ≧ 80%) had longer progression-free survival (PFS) PD-L1 ≧ 80% v.s. PD-L1 < 80%, PFS, median, 11.2 v.s 7.0 months, hazard ratio [HR]: 0.52, p = 0.03).

In 229 pts with stage II-IIIA PD-L1 TC ≥50% NSCLC, the OS HR was 0.43 (95% CI: 0.24, 0.78); after excluding 20 pts with known EGFR/ALK+ status, the OS HR was 0.42 (95% CI: 0.23, 0.78). The OS subgroup analysis is presented in the table….Pts with stage II-IIIA PD-L1 TC ≥50% NSCLC derived OS benefit with atezo vs BSC. OS benefit was consistent across most pt subgroups, albeit with limited numbers in this exploratory analysis. The atezo safety profile remained unchanged.

Confirmed ORR was 30.4% (95% confidence interval [CI]: 13.2, 52.9), with all seven patients achieving partial response. DCR was 78.3% (95% CI: 56.3, 92.5), median PFS was 5.4 months (95% CI: 2.8, 8.6), and median OS was not reached (95% CI: 6.7, not estimable). Sitravatinib plus tislelizumab demonstrated a manageable safety and tolerability profile as well as antitumor activity in patients with PD-L1+, locally advanced or metastatic squamous NSCLC who had not received prior systemic treatment in the metastatic setting.

Sitravatinib plus tislelizumab showed a manageable safety and tolerability profile and demonstrated antitumor activity in patients with PD-L1+, locally advanced or metastatic non-squamous NSCLC who had not received prior systemic treatment in the metastatic setting.

Between Jan 14, 2019, and Jun 18, 2021, 96 patients (pts) were enrolled and 13 pts were excluded due to inclusion violations. At data cutoff (Feb 24, 2022), 83 pts. (demographics are shown in Table 1) were available for efficacy and safety analysis...Confirmed ORR was 30.4% (95% confidence interval [CI]: 13.2, 52.9), with all seven patients achieving partial response. DCR was 78.3% (95% CI: 56.3, 92.5), median PFS was 5.4 months (95% CI: 2.8, 8.6), and median OS was not reached (95% CI: 6.7, not estimable).Sitravatinib plus tislelizumab demonstrated a manageable safety and tolerability profile as well as antitumor activity in patients with PD-L1+, locally advanced or metastatic squamous NSCLC who had not received prior systemic treatment in the metastatic setting.

This retrospective study analyzed a cohort of Hispanic patients (N=103) diagnosed with mNSCLC from the US and seven Latin American countries (LATAM) treated with immune checkpoint inhibitors (ICI) alone or in combination...OS was significantly longer among patients with tumors with PD-L1 ≥50% (30.9 months), and different from those with PD-L1 1-49% (22.0 months), and PD-L1 <1% (12.0 months) (p=0.0001).

We enrolled advanced NSCLC patients who harbored sensitizing EGFR mutation and were treated first-line with osimertinib between 2017 and 2021….In patients with ECOG PS 0 to 1, PD-L1 < 50% and exon 19 deletion had respectively better PFS with an adjusted HR (aHR) of 0.14 (95% CI, 0.04 to 0.50; p = 0.002), an aHR of 0.19 (95% CI, 0.06 to 0.67; p = 0.009) and an aHR of 0.24 (95% CI, 0.10 to 0.57; p = 0.001).

DFS in PD-L1 TC >/= 50% (VENTANA SP263 assay) stage II-IIIA (UICC/AJCC v7) pts was a prespecified secondary endpoint....Median follow-up was 34.2 mo (21 Jan 2021 cutoff). See the table for DFS subgroup data. Safety in PD-L1 TC >/= 50% stage II-IIIA pts was consistent with that of the overall study population and known safety profile of atezo….IMpower010 pts with PD-L1 TC >/= 50% stage II-IIIA NSCLC derived DFS benefit with atezo vs BSC at the interim DFS analysis....The tolerability profile of atezo was in line with the overall population, demonstrating a positive benefit-risk profile.

KRAS status was determined in 107 pt: 46% harbored KRAS G12C and 54%KRAS nonG12C. High PD-L1 was detected in 37% of cases, predominantly in KRASG12C vs nonG12C (56% vs 44% p¼0.2). A total of 65 pt (54%) were treated with IT for advanced disease; 42% in 1stline, 46% in 2ndand 12% in 3rd. 81% received anti-PD-1,16% anti-PD-L1 and 3% anti-CTLA-4. After median follow up of 63m, the median progression free survival (mPFS) to IT was 10.1m vs 3.3m in KRAS G12C vs nonG12C,respectively (p¼0.07); the mOS was 17.9m vs 18.6m in KRAS G12C vs nonG12C(p¼0.13). KRAS mut represent an heterogenous group of NSCLC. Although nostatistically significant, pt with KRAS G12C mut tended to present better mPFS to ITcompared to nonG12C pt, with no impact on OS.

We report results from the phase 1b JAVELIN PARP MEKi trial (NCT03637491) evaluating avelumab + binimetinib in patients with mPDAC....Tumor shrinkage was associated with higher baseline PD-L1 expression, higher number of CD8+ TILs, and MEK1/2, PIK3CA, and RNF43 alterations...

Patients with aMM relapsing after at least one line of platinum doublet chemotherapy and not previously pre-exposed to IO were treated with a combination of oral nintedanib (150mg BID) &amp; IV pembrolizumab (200mg Q3W) with a 7 days nintedanib lead-in preceding pembrolizumab initiation....Patients with DCR at 6 months had significantly higher percentage of PDL1 expression on tumor cells (by Immuno-Histo-Chemistry, antibody clone SP263)...

Survival analyses according to PD-L1 using the combined positive score (CPS, Ventana SP263 assay) was conducted….Exploratory analysis of PD-L1 expression was not associated with improved survival outcomes.

Eligible patients with unresectable locally advanced or metastatic UC...Japanese patients (n=73) were randomized to receive Ave + BSC (n=36) or BSC alone (n=37); 52.8% vs 62.2% had PD-L1+ tumors, respectively. Median OS (95% CI) was 24.7 months (18.2-not estimable [NE]) with Ave + BSC vs 18.7 months (12.8-33.0) with BSC alone (HR, 0.81 [95% CI; 0.409-1.585]) in all randomized patients...

Patients with Stage IIIB/IV lung adenocarcinoma harbouring a sensitising mutation in EGFR and treated with first-line, first or second generation TKI…Compared to patients with PD-L1 low/negative tumours (n=145, 86%, those with high PD-L1 (n=23; 14%) had significantly shorter PFS (6.6 vs 13.0 months, HR 2.6 95% CI 1.6-4.2, p<0.0001)...high PD-L1 expression was associated with early resistance to 1st generation EGFR TKIs, and predicts shorter survival.

Single-agent tislelizumab demonstrated antitumor activity in advanced, previously treated HCC (ORR=13%; CB [PR+SD >6 months]=31%, median PFS=3.3 months; median OS=13.3 months). PD-L1+ (TC≥1%) prevalence and GEP showed different patterns in samples collected before and after sorafenib exposure....In sorafenib-exposed samples, PD-L1 expression was positively correlated with CB (P=0.0027) and a trend of longer PFS (HR=0.56, 95% CI:0.28–1.13). ORR was higher in PD-L1+ than PD-L1− sorafenib-exposed samples (23.8% vs 0%; P=0.049).

Patients with Stage IIIB/IV lung adenocarcinoma harboring a sensitizing EGFR mutation and treated with first‐line, first or second‐generation TKI...28% received first‐line gefitinib...Compared to patients with PD‐L1 low/negative tumours those with high PD‐L1 (n = 9; 13%) had significantly shorter PFS...OS (10.8 vs 25.8 months, HR 0.22 95% CI 0.09‐0.58, P = .001).

Patients with Stage IIIB/IV lung adenocarcinoma harboring a sensitizing EGFR mutation and treated with first‐line, first or second‐generation TKI...69% received erlotinib...Compared to patients with PD‐L1 low/negative tumours those with high PD‐L1 (n = 9; 13%) had significantly shorter PFS...OS (10.8 vs 25.8 months, HR 0.22 95% CI 0.09‐0.58, P = .001).

Patients with Stage IIIB/IV lung adenocarcinoma harboring a sensitizing EGFR mutation and treated with first‐line, first or second‐generation TKI...3% received afatanib...Compared to patients with PD‐L1 low/negative tumours those with high PD‐L1 (n = 9; 13%) had significantly shorter PFS...OS (10.8 vs 25.8 months, HR 0.22 95% CI 0.09‐0.58, P = .001).

In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051).

In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051).

In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051).

In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051).

In all solid tumor types, pts with PD-L1-positive tumors experienced clinical benefit with significantly higher ORR (39.6% vs 14.5%, p=0.0025) and longer PFS (p=0.0241). ORR was higher for PD-L1 positive (TC≥25%) pts with lung cancer (66.7% vs 20.0%, p=0.051).

Pts with low PD-L1 and low TMB had worse OS compared to pts with high PD-L1 or high TMB.

Pts with low PD-L1 and low TMB had worse OS compared to pts with high PD-L1 or high TMB.

...we report a rare case of ESCC with asymptomatic brain metastasis. The combined positive score (CPS) of programmed cell death-ligand 1 (PD-L1) from the primary tumor was 2 by DAKO 22C3 and 3 by VENTANA SP263....Given that his ESCC was positive for PD-L1, toripalimab, one of ICIs, was recommended for his asymptomatic solitary brain metastasis. From August 2019 to October 2020, he received 15 3-week cycles of toripalimab. A follow-up brain MRI revealed that the brain metastasis was replaced by a necrotic area (Figure 2)....By the last revision of this article, the patient was still on toripalimab with a stable disease at the primary site as well as a good cognitive function.