TEST:

VENTANA PD-L1 (SP142) Assay

Roche...today announced that the European Commission has approved Tecentriq® (atezolizumab) as a first-line (initial) treatment for adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.

...Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced today that it has obtained regulatory approval for its humanized anti-PD-L1 monoclonal antibody, Tecentriq® Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)] from the Ministry of Health, Labour and Welfare (MHLW) for additional dosing for the treatment of chemotherapy-naïve PD-L1-positive unresectable advanced or recurrent non-small cell lung cancer (NSCLC)....This approval is based on the results from the phase III IMpower110 study. The study met its primary endpoint in an interim analysis showing that Tecentriq monotherapy improved overall survival (OS) by 7.1 months compared with chemotherapy alone in patients with high PD-L1 expression...

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Non-Small Cell Lung Cancer (NSCLC)....in combination with paclitaxel protein-bound for the treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA approved test.

TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Urothelial Carcinoma....for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who: are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 5% of the tumor area), as determined by an FDA-approved test.

Atezolizumab is recommended, within its marketing authorisation, as an option for untreated metastatic non-small-cell lung cancer (NSCLC) in adults if...their tumours have PD-L1 expression on at least 50% of tumour cells or 10% of tumour-infiltrating immune cells....Pembrolizumab in combination with chemotherapy may also be offered.

Atezolizumab is recommended, within its marketing authorisation, as an option for untreated metastatic non-small-cell lung cancer (NSCLC) in adults if...their tumours have PD-L1 expression on at least 50% of tumour cells or 10% of tumour-infiltrating immune cells

NIVO effect was larger in pts with tumors with increasing PD-L1 expression, with a ΔpCR rate (unweighted rate difference between arms A and B) of 16.6% in CPS ≥ 1 (40.4% vs 23.8% in arms A/B; 95% CI, 2.8 to 29.4), 32.4% in CPS ≥ 10 (65.7% vs 33.3% in arms A/B; 95% CI, 7.3 to 52.3), and 52.3% in CPS ≥ 20 (78.9% vs 26.7% in arms A/B; 95% CI, 18.6 to 72.4)....Greater PD-L1 expression was associated with higher pCR and RCB 0–1 rates, suggesting that pts with PD-L1+, high-risk, ER+/HER2− primary BC can achieve substantial pCR rates with the addition of NIVO to NACT.

Roche...today announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq® (atezolizumab) as adjuvant treatment following surgery and platinum-based chemotherapy for people with non-small cell lung cancer (NSCLC) whose tumours express PD-L1≥1%, as determined by an FDA-approved test,

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.

...atezolizumab versus docetaxel by programmed death-ligand 1 (PD-L1) status, in patients with previously treated metastatic NSCLC....In the 22C3-BEP, overall survival (OS) benefits with atezolizumab versus docetaxel were observed across PD-L1 subgroups; benefits were greatest in SP142-defined PD-L1–high (TC3 or IC3: HR 0.39; 95% CI, 0.25-0.63) and 22C3-defined PD-L1–high (TPS ≥50%: HR 0.56, 95% CI, 0.38-0.82) and –low (TPS 1%-<50%: HR 0.55; 95% CI, 0.37-0.82) groups. Progression-free survival (PFS) improved with increasing PD-L1 expression for both assays.

Roche...today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq® (atezolizumab) as a first-line (initial) treatment for adults with metastatic non-small cell lung cancer (NSCLC) whose tumours have high PD-L1 expression...

PFS prognosis (assessed in the placebo + CPB arm) was improved in patients with BRCA1/2m (hazard ratio [HR] 0.62, 95% CI 0.46–0.84) and HRD (HR 0.63, 95% CI 0.49–0.80) tumors. There was a suggested association between PD-L1+ and HRD (HRD prevalence: 40% vs 25% in PD-L1+ vs PD-L1– subgroups...

...in pts with PD-L1-expressing immune cells on ≥5% of the tumor area (IC2/3 per VENTANA SP142 IHC assay….Pts were randomized 1:1:1 to Arm A (atezo + plt/gem [not reported here]), B or C....Exploratory subgroup analyses suggested that OS for IC2/3 pts may be higher in Arm B vs C. In ITT pts, ORR was higher in Arm C, but median DOR was longer in Arm B....benefit of atezo monotherapy as first-line treatment for PD-L1 IC2/3 cisplatin-ineligible mUC..

NON-SUPPORTIVE EVIDENCE: Patients had PD-L1–selected (≥1% PD-L1 on TC or IC [TC1/2/3 or IC1/2/3]; VENTANA SP142 IHC assay), chemotherapy-naive, stage IV NSCLC and an ECOG PS of 0-1. Patients were randomised 1:1 to Arm A (atezolizumab 1200 mg IV q3w)...At the final OS analysis, IMpower110 did not show statistical significance in TC2/3 or IC2/3-WT patients. Exploratory updated analysis in TC3 or IC3-WT patients showed continued clinically meaningful OS benefit in the atezolizumab vs chemotherapy arm.

...higher TMB was associated with OS benefit in PD-L1+ TNBC treated with Az + nP…

PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC.

PD-L1 IC2/3 was associated with significantly longer OS for atezo mono vs placebo + PBC and a combination of PD-L1 IC2/3, and high TMB (> 10 muts/Mb) identified a pt subset (≈ 14% of BEP) with particularly favorable outcomes with atezo mono vs placebo + PBC; similar results for PD-L1 and TMB were not seen with atezo + PBC vs placebo + PBC.

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

From August 2019 to June 2021, 90 patients (HR+HER2- 45 pts/TNBC 45 pts)...PFS rate at 6-months was 49.6% and 24.1% in patients with HR+HER2- and TNBC group, respectively. Median PFS was 5.6 months (95% CI: 4.3-6.8) and 3.0 months (95% CI: 1.3-4.7) for HR+HER2- and TNBC group, respectively. ORRs were 53.3% (CR:0, PR: 24) for HR+HER2- and 21.8% (CR1, PR: 12) for TNBC. Patients with PD-L1+ tumors (PD-L1 expression ≥ 1% on TC or IC) had similar ORR compared to PD-L1- tumors (ORR 50% vs. 53.8% in HR+HER2-, 30.8% vs. 29.0% in TNBC). In this parallel phase II clinical trial, the addition of nivolumab to eribulin showed promising efficacy and tolerable safety profile in previously treated HER2- MBC.

Of 9 response-evaluable pts (10-15 mg/kg atezo and ≥ 12 wk followup; 1 pt without RECIST measurable disease at baseline was evaluable for PFS/OS but not response), 2 pts (22%) had a PR….Of the 10 evaluable for PFS/OS, 1 pt was IC0/1, 9 were IC2/3 and all belonged to an RNA-defined immunoreactive subgroup of OC that is associated with T cell activation and high PD-L1 expression. Atezo responders were IC2/3 and had low baseline CA125 levels vs pts who progressed.

A second NGS assay found a possible resistance mutation of c.6012T>G (p.F2004L)...nivolumab (200 mg, d1), nedaplatin (120 mg, d1), and pemetrexed (800 mg, d1) every 3 weeks were started to administered to the patient...The patient achieved a partial response to ICT...Unfortunately, it was not long before the disease progressed again...patients with PD-L1-positive ROS1-rearrangement NSCLC, and suggests that ICT might not be a better option than lorlatinib regimen in the second-line setting.

A second NGS assay found a possible resistance mutation of c.6012T>G (p.F2004L)...repeat biopsy tissue sample from the supraclavicular lymph node showed that the expression of PD-L1 in both tumor cells and immune cells was 10%...lorlatinib, which is potent for brain metastases, was administered to the patient (100 mg orally once a day)....previously enlarged lymph nodes also shrank to normal size. The patient continued to take lorlatinib and has not experienced disease progression so far...

We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer...Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage III A/B or IV A/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage III B or IV triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.

We report a case in which atezolizumab was efficiency in PD-L1 (SP142)-positive lung and breast double cancer...Pretreatment diagnosis was lung adenocarcinoma, cT2a, N2/3, M1b/1c(HEP, OSS), Stage III A/B or IV A/B(PD-L1 positive), and right breast cancer, T4b, N2, M0/1 (HEP, OSS, LYM), Stage III B or IV triple-negative(PD-L1 positive)double cancer. We underwent surgery(mastectomy with axillar lymph nodes dissection), followed by immunochemotherapy(atezolizumab, carboplatin, paclitaxel)and it was efficiency.