TEST:

PD-L1 IHC 22C3 pharmDx

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated...in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated...in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Libtayo® (cemiplimab) is now approved in Canada for the first-line treatment of adult patients with non-small cell lung cancer (NSCLC) expressing PD-L1 in ≥ 50% of tumour cells (Tumour Proportion Score [TPS] ≥ 50%), as determined by a validated test with no EGFR, ALK, or ROS1 aberrations...

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...Cervical cancer...in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. (1.11, 2.1)

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated...Triple-Negative Breast Cancer (TNBC)...in combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by an FDA approved test.

LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:...for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations...

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:…for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:…as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

for the first-line treatment of patients with NSCLC whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved test, with no EGFR, ALK or ROS1 aberrations.

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:...stage III where patients are not candidates for surgical resection or definitive chemoradiation, or...metastatic....as a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy.

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...Cervical cancer...in combination with chemotherapy, with or without bevacizumab, for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. (1.11, 2.1)...for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test...

KEYTRUDA is a programmed death receptor-1 (PD-1)-blocking antibody indicated:...as a single agent for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended approval of KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) and who have not received prior chemotherapy for metastatic disease.

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.

...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.

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

559 patients with untreated metastatic, squamous NSCLC to receive...pembrolizumab or saline placebo...the patients also received carboplatin and either paclitaxel or nanoparticle albumin-bound [nab]–paclitaxel...the median progression-free survival was 6.4 months (95% CI, 6.2 to 8.3) in the pembrolizumab-combination group and 4.8 months (95% CI, 4.3 to 5.7) in the placebo-combination group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.45 to 0.70; P<0.001) (Figure 2A)....The progression-free survival benefit of the pembrolizumab combination was observed in all prespecified subgroups (Figure 2B), with incremental improvements noted with increasing PD-L1 tumor proportion score (median progression-free survival among patients with a PD-L1 tumor proportion score of <1% in the pembrolizumab-combination group vs. the placebo-combination group....Prolongation of overall survival of a consistent magnitude was observed across the categories of PD-L1 tumor proportion score (<1%, 1 to 49%, and ≥50%)...

Patients (aged ≥20) with pathologically proven NSCLC harboring PD-L1 expression ≥1% (22C3), resectable clinical stage IB-IIIA NSCLC, and performance status of 0 to 1 were eligible. Patients received two cycles of pembrolizumab (200 mg/body) and ramucirumab (10 mg/kg) every three weeks....The results of this study demonstrated that this new neoadjuvant combination of ICI and anti-VEGF agent (pembrolizumab and ramucirumab) is feasible and showed encouraging results.

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).

Overall, 18 pts with MSI/dMMR resectable cT2-4 any N GAC/GEJAC were recruited in Cohort 1….Among 15 evaluable patients, 1 had disease progression and 14 underwent resection. pCR rate was 60% (9/15) and major-complete pathological response (<10% viable cells) was 80%....Pre-operative T300/D for 3 months was safe and provided promising proof of efficacy in MSI, dMMR GAC/GEJAC pts.

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).

Key eligibility criteria were HR+ HER2- MBC...Eligible patients received 200 mg pembrolizumab IV every 3 weeks plus AI...Responses were 10% partial response and 15% stable disease, resulting in a clinical benefit rate (CBR) of 20% at 6 months. Median follow-up time was 40.1 months (range 31.3 – 46.8 months). Median progression free survival was 1.8 months (95% CI 1.6, 2.6) and median overall survival was 17.2 months (95% CI 9.4, NA).

Tiragolumab plus atezolizumab showed a clinically meaningful improvement in objective response rate and progression-free survival compared with placebo plus atezolizumab in patients with chemotherapy-naive, PD-L1-positive, recurrent or metastatic NSCLC.

...we retrospectively analyzed the baseline PD-L1 expression levels using immunohistochemistry 22C3 assay of tissue samples from 128 patients with ALK-rearranged advanced lung adenocarcinoma who were treated with first-line crizotinib….A subset of patients with ALK-rearranged NSCLC having high baseline PD-L1 expression level (TPS of ≥50%) had poorer survival outcomes despite crizotinib therapy.

This phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer...PD-L1 expression was assessed by immunohistochemistry...All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%).

Of 37 response evaluable patients, 22 patients (59.5%) achieved an ORR including 18 (48.6%) patients with CR...We assessed PD-L1 (22C3) expression by combined positivity score (CPS). The median CPS was 40.0, patients with CPS ≥ 30 exhibited benefit...Sintilimab combined with Chidamide showed manageable safety profile and yielded effective antitumor activity, durable response in patients with r/r ENKTL for the first time.

Patients with nonsquamous NSCLC were eligible...Patients in cohort A received 1 cycle of carboplatin...paclitaxel...and pembrolizumab...Patients in cohort B had nonsquamous NSCLC and received 3 cycles of cisplatin (75 mg/m2) and pemetrexed (500 mg/m2) plus pembrolizumab...In subgroup analyses in cohort A, ORR was achieved in 14 patients (66.7%) with PD-L1 TPS less than 1% and 50 (75.8%) with PD-L1 TPS 1% or greater... In cohort B, ORR was achieved in 20 patients (71.4%) with PD-L1 TPS less than 1% and in 29 (72.5%) with PD-L1 TPS 1% or greater...

Subgroup analysis by PD-L1 tumor expression status indicated better efficacy outcomes in patients with PD-L1+ tumors versus those with PD-L1− tumors [ORR, 28.4% (95% CI: 18.5–40.1) vs 17.3% (95% CI: 9.6–27.8); PFS, 4.2 months (95% CI: 3.5–6.1) vs 3.9 months (95% CI: 2.3–4.4)...in patients with PD-L1+ tumors, the study-drug combination also demonstrated promising antitumor activity in patients with PD-L1− tumors. These results support further clinical development of eribulin plus pembrolizumab as a potential antitumor strategy for patients with mTNBC.

... The primary site was in upper tract UC in 50%; 50% had visceral metastases (mets), including 36% with liver mets; HER2 expression was positive (IHC 3+ or 2+ ISH+) in 28%, and 43% PD-L1 CPS≥10. A total of 36 pts is anticipated to be enrolled by Apr 2021. No dose limiting toxicity was reported and the recommended dose for RC48-ADC was 2mg/kg. At data cutoff, 10/14 patients were evaluable for response, with 8 PR, 1 SD (tumor shrinking), and 1 PD. The objective response rate (ORR) was 80%, and disease control rate (DCR) was 90%.RC48-ADC in combination with toripalimab had a good tolerance and

...The primary site was in upper tract UC in 50%; 50% had visceral metastases (mets), including 36% with liver mets; HER2 expression was positive (IHC 3+ or 2+ ISH+) in 28%, and 43% PD-L1 CPS≥10. A total of 36 pts is anticipated to be enrolled by Apr 2021. No dose limiting toxicity was reported and the recommended dose for RC48-ADC was 2mg/kg. At data cutoff, 10/14 patients were evaluable for response, with 8 PR, 1 SD (tumor shrinking), and 1 PD. The objective response rate (ORR) was 80%, and disease control rate (DCR) was 90%...RC48-ADC in combination with toripalimab had a good tolerance and

...EGFR-mutant, advanced lung adenocarcinoma patients who received first-line EGFR-TKIs and evaluated the PD L1 tumor proportion score...In multivariate analysis, PD-L1 TPS ≥ 50% was independently associated with a significantly shorter PFS in the overall population (hazard ratio [HR] = 2.64, p = 0.004), and associated with shorter OS in patients with exon 19 deletion (HR = 2.55, p = 0.041) compared with PD-L1 TPS < 50%

In KEYNOTE-180, data in a small number of patients suggested that measures of inflammation, like PD-L1 and GEP, may enrich for responses to pembrolizumab. In SCC, some trends toward enrichment were observed for both biomarkers, although the trend was stronger for PD-L1 CPS ≥10 (tables 1, 2).

In NSCLC patients with PD-L1 expression ≥50%, pembrolizumab improved progression-free and overall survival compared to chemotherapy.

ERI + PEMBRO has activity in pts with mTNBC. There was a trend toward more robust activity for the combination among patients with PD-L1+ tumors compared to PD-L1- tumors in the first-line setting (Stratum 1); whereas, in the later-line setting (Stratum 2) similar survival outcomes were observed among the PD-L1+ and PD-L1- pts.

Among pts with PD-L1 IHC status by 22C3 pharmDx assay (n = 24; 71%), the majority of pts with a response or stable disease (SD) had PD-L1 CPS status < 20 (11 of 15 pts including 1 SD pt with CPS < 1). Median PFS was 5.6 months (95% CI: 3.9, 6,2). Median OS was not reached at time of analysis (95% CI: 8.2, NR); 6-month OS rate was 84% (95% CI: 66, 93).

This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC...At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo...With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]).

The median PFS was significantly higher in RAD51Bme+ patients (p = 0.0216; Figure 3A). Furthermore, patients with RAD51Bme+ disclosed a lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025) compared with RAD51Bme-….PD-L1+ and RAD51Bme+ are promising biomarkers to predict response to PD-1 blockade rather than overall prognostic factors in NSCLC’s patients.

The median PFS was significantly higher in RAD51Bme+ patients (p = 0.0216; Figure 3A). Furthermore, patients with RAD51Bme+ disclosed a lower risk of disease progression (HR 0.37; 95% CI: 0.15–0.88; p = 0.025) compared with RAD51Bme-….PD-L1+ and RAD51Bme+ are promising biomarkers to predict response to PD-1 blockade rather than overall prognostic factors in NSCLC’s patients.

Pembro is given 200mg q3w x3 cycles. Pathologic complete response (pT0) in ITT population is the primary endpoint (EP)….pT0 responses were obtained in 10 (52.6%) pts with CPS≥21%...

Pembro is given 200mg q3w x3 cycles. Pathologic complete response (pT0) in ITT population is the primary endpoint (EP)….8/8 pts (100%) with DDR/RB1 GA and CPS≥21% achieved pT0.

Pembro is given 200mg q3w x3 cycles. Pathologic complete response (pT0) in ITT population is the primary endpoint (EP)….8/8 pts (100%) with DDR/RB1 GA and CPS≥21% achieved pT0.

HER2+ (pre-T testing) PD-L1-unselected GEA pts were enrolled….Of 57 evaluable pts to date in expansion (30 NA and 27 A), best ORR was 16% and disease control rate (DCR) was 54%. Both ctDNA ERBB2 amp and PD-L1 positivity predicted response (24% vs. 0% [p = .0655] and 36% vs. 5% [p = .0367], respectively)....M+P is a well-tolerated regimen with antitumor activity in 2nd line HER2+ GEA.

In this small population, using a prototype assay scoring PD-L1 expression as the percentage of inflammatory and tumor cells staining for PD-L1, there was evidence of an increasing probability of response (one-sided P = .028 for ORR) and a reduction in the hazard (one-sided P = .012 for PFS) with increasing expression of PD-L1....Using a prototype assay, there was a trend toward clinical benefit with pembrolizumab and increasing PD-L1 expression.

Patients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel….Two-year OS and PFS rates for pembrolizumab–chemotherapy versus placebo–chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively....HRs for OS favored pembrolizumab–chemotherapy across most patient subgroups, including patients with PD-L1 TPS greater than or equal to 1% and PD-L1 TPS less than 1% (Fig. 2B).

Endpoints were pCR rate by ypT0 ypN0 and ypT0/Tis ypN0 and objective response rate (ORR; RECIST v1.1) after the first 4 cycles of NAT (taxane±carboplatin+pembro) by MRI....Higher quantities of pretreatment sTILs and PD-L1 CPS and on-treatment sTILs were significantly associated with higher pCR rates and ORR in primary TNBC treated with pembro and NAT.

This phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer...PD-L1 expression was assessed by immunohistochemistry...All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%).

This phase I/II, single-arm clinical trial studied concurrent carboplatin and pembrolizumab in recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer...PD-L1 expression was assessed by immunohistochemistry...All PD-L1-positive patients achieved PR (3/7, 42.8%) or SD (4/7, 57.2%).

66 patients with non-squamous NSCLC treated with PD-1/PD-L1 inhibitors at MDACC (61% pembrolizumab, 24% nivolumab, 8% atezolizumab, 5% durvalumab/tremelimumab) with available STK11/LKB1 NGS-based genomic profiling and positive tumor cell PD-L1 expression...STK11/LKB1 genomic alterations are associated with de novo resistance to PD-1/PD-L1 inhibitors even among PD-L1-positive non-squamous NSCLC patients, suggesting that their effect is at least partially independent of PD-L1 expression.

Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression.

Patients with R/M HNSCC who failed at least one line of prior treatment including a PD-1 inhibitor and for whom no surgical or radiation curative options existed were eligible for the study. Patients received niraparib (200 mg daily) beginning one week prior to initiation of dostarlimab (500 mg q3wks x4 followed by 1000 mg q6wks)....The patient with a PR remains on treatment past 24 months, was PD-L1 positive, had low TMB and no DDR deficiency.

We document the case of a 63-year-old patient with NSCLC harbouring a rare BRAF E501Q mutation, who had prolonged response to immunotherapy combined with chemotherapy in Vietnam. The patient was diagnosed with metastatic PD-L1-negative lung adenocarcinoma and received pembrolizumab plus chemotherapy as first-line treatment. After completing 35 cycles of pembrolizumab and pemetrexed, his disease has remained stable during the treatment-free follow-up period, and he is alive 38 months after treatment initiation at the latest follow-up...

We present the case of a 45-year-old...A transthoracic biopsy revealed a non-small-cell lung carcinoma….The immunohistochemical analysis with the monoclonal mouse anti-human PD-L1, Clone 22C3, revealed PDL1 expression in 90-100% of the cells….the patient fully recovered and started second-line treatment with platinum-containing doublet chemotherapy (cisplatin 80 mg/m2 IV and paclitaxel 175 mg/m2 IV every three weeks). According to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1 criteria, the thoracic CT after three cycles showed a partial response of the tumor (dimensions of 8.5 cm × 4.1 cm) and lymph nodes.

This 64-year-old male patient...whose path report showed lung adenocarcinoma. FoundationOne CDx panel demonstrated MET exon 14 skipping mutation (3038+3A>G, allelic fraction > 80%) plus MET amplification (12 copy numbers). PD-L1 expression (22C3) was 90%....Two months after tepotinib was started, complete radiologic response was achieved, and patient continues on treatment without evidence of disease after 1 year.

...we present two cases of RET-rearranged NSCLC patients with high PD-L1 expression (>50%), treated with pembrolizumab within routine clinical practice....A 65-year-old woman...diagnosis of adenocarcinoma with 70% of PD-L1 TPS...Molecular testing confirmed CCDC6-RET fusion...pembrolizumab treatment was initiated in February 2020. Progressive disease (mediastinal lymph nodes progression, new lung nodules, bone lesions, and liver metastases) was found on CT which was performed three months later in May 2020...

...we present two cases of RET-rearranged NSCLC patients with high PD-L1 expression (>50%), treated with pembrolizumab within routine clinical practice....A 65-year-old woman...diagnosis of adenocarcinoma with 70% of PD-L1 TPS...Molecular testing confirmed CCDC6-RET fusion...pembrolizumab treatment was initiated in February 2020. Progressive disease (mediastinal lymph nodes progression, new lung nodules, bone lesions, and liver metastases) was found on CT which was performed three months later in May 2020—the patient received four doses of pembrolizumab (200 mg i.v. every 21 days) (Figure 4). Then, palliative chest radiotherapy was performed. Afterwards, due to the poor performance status...

...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.

...a 69-year-old male with a 15-year smoking history went to our hospital...SqCLC was confirmed by pathological examination and immunohistochemistry...The second NGS analysis of the whole blood sample with a large panel (Genetron Health, Beijing, China), including 824 somatic genes, suggested EGFR G719A and S768I mutations...Since an immunohistochemistry study of the right kidney metastasis showed a PD-L1 tumor proportion score (TPS) of 20% (22c3 antibody on the Dako Link-48 platform) (Figure 1B), single-agent camrelizumab (200 mg every 2 weeks) was started...The patient remained in PR after 43 cycles (Figure 3B) and was about to receive the 50th cycle of monotherapy with camrelizumab as of the time of writing of this case report (November 20, 2021), with a PFS of 24.4 months.

The patient had 5% tumor PD-L1 positivity with 22C3 pharmDx and received pembrolizumab (200 mg every 21 days) for 13 cycles….The disease remained well controlled...Our case report suggests that the use of anti-PD-1 therapy does show efficacy in the treatment of PPA and may provide a viable treatment option for patients.

A forty-year-old Filipino woman presented to our center with recurrent VCCC...Complete clinical response...and RECISTv1.1 PR on PET-CT scan...was seen after 3 cycles of pembrolizumab...our patient with VCCC harboring a high PD-L1 CPS experienced durable and meaningful response to fifth-line pembrolizumab.

A 71-year-old never-smoker Caucasian man...A biopsy from the lung mass revealed poorly differentiated adenocarcinoma of lung primary...Immunohistochemistry (IHC) for PD-L1...demonstrated tumor proportion score of 100%... Next generation sequencing...revealed KIF5B-RET fusion (4.9% of DNA)...In addition, concurrent TP53 (13.4%) and AR (0.2%) mutations were reported. FISH confirmed RET rearrangement...pembrolizumab...was initiated....Follow-up MRI and CT scan at 6 months after treatment showed a complete response...

A 52-year-old male never-smoker...The tumor was positive for EGFR, EGFR P719A mutation. The PD-L1 expression have been tested by FDA-approved 22C3 antibodies, and PD-L1 expression level of 95%. The patients received anti-PD-1 combination treatment. He has reached partial response (PR) after 4 cycle treatment. After ten months, he has the opportunity to receive the operation....NSCLC patients harboring sensitizing oncogenic mutations may potentially benefit from anti-PD-1/L1 especially for those with positive indicators of immunotherapy with strong positive PD-L1 expression.

Liquid biopsy test reported actionable alterations in ARID1A gene...The patient was treated with immunotherapy, and showed a treatment response lasting for 19 months until a new metastasis appeared at the right deltoid muscle. Genomic analysis of a sample of this metastasis confirmed PD-L1 positivity of greater than 50% with CD8+ T cells expression and showed MSI with a deleterious c.298C>T (p.R100*) MLH1 gene mutation.

Liquid biopsy test reported actionable alterations in ARID1A gene...Nivolumab 3 mg/kg intravenously every 2 weeks was administered for 38 cycles....The patient was treated with immunotherapy, and showed a treatment response lasting for 19 months until a new metastasis appeared at the right deltoid muscle. Genomic analysis of a sample of this metastasis confirmed PD-L1 positivity of greater than 50% with CD8+ T cells expression and showed MSI with a deleterious c.298C>T (p.R100*) MLH1 gene mutation.

Liquid biopsy test reported actionable alterations in ARID1A gene...Genomic analysis of a sample of this metastasis confirmed PD-L1 positivity of greater than 50% with CD8+ T cells expression and showed MSI with a deleterious c.298C>T (p.R100*) MLH1 gene mutation....In December 2018, a PR was achieved with cisplatin plus pemetrexed reintroduction since October 2018 (Fig. 1), but the disease progressed shortly after. Immunotherapy rechallenge and vinorelbine did not succeed either.