Keytruda as monotherapy is indicated for the first line treatment of metastatic non small cell lung carcinoma in adults whose tumours express PD L1 with a ≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

...Exploratory Objectives(1) To assess patient-reported outcome (PRO) of disease-related symptoms utilizing the disease-related symptoms – physical (DRS–P) subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index 18 (FOSI-18) Changes and using Euro-Quality of Life 5D (eEQ-5D) tool.(2) To investigate the relationship between PD-L1 expression and response to Pembrolizumab treatment utilizing newly obtained or archival FFPE tumor tissue.Additional Biomarkers Research 1. ...

...Programmed cell death ligand 1 (PD-L1) expression`PD-L2 expression`Changes in T cell activation`Overall survival...

...Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining`Overall Survival (OS)`Best Overall Response (BOR)`Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1`Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1`Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1...

...Likewise, the PD activity of ICT01 (by dose and patient population) will include the change from baseline in counts and activation status of Vγ9Vδ2 T cells and other immune cells in the peripheral blood, peripheral blood mononuclear cells (PBMCs) and tumor biopsies, circulating cytokine levels (including IFN gamma, TNF alpha, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17a and MCP-1), and expression of PD-L1, PD-1 and other immune cell markers in tumor biopsies and PBMCs. ...

...Progression free survival (PFS)`Response rate`Adverse events`Exploratory Objective: relationship between PD-L1 expression and response to Pembrolizumab treatment.`...

...The percentage of participants who experienced CR or PR per RECIST 1.1 by BICR is reported here as the ORR for the subgroup of participants in Cohort A and Cohort B who had a PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as CPS ≥10.`...

...Lower H-scores represent lower expression of PD-L1 in the tumor sample, while higher scores represent stronger expression of PD-L1 in the tumor samples....

...PD-L1 Expression in Preserved Tissue Obtained at the Time of Initial Diagnosis for Patients...

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%).

To address this lack in knowledge, we evaluated therapeutic responses to PARP inhibitors, checkpoint inhibitors, and combinations using ovarian cancer patient-derived 3D tumor spheroids...PD-L1 expression was associated with response to pembrolizumab…

In cohorts A and B, ORR (95% CI) was 8.1% (5.2, 11.9) and 9.9% (4.6, 17.9) in the total population, 6.9% (2.8, 13.8) and 10.2% (3.4, 22.2) in pts with CPS ≥1, and 11.6% (3.9, 25.1) and 18.2% (5.2, 40.3) in pts with CPS ≥10. Median DOR (range) was 8.3 (3.9 to 35.4+) mo in cohort A and 23.6 (3.3+ to 32.8+) mo in cohort B.

We present the rare case of a 23 year old woman with small cell carcinoma of the right ovary…PDL-1 testing showed a CPS (combined positive score) of 2. In November 2020 immunotherapy with pembrolizumab q21d was started. MRI in December 2020 showed remission of hepatic metastases under therapy with pembrolizumab...To date, in April 2023, therapy with pembrolizumab is being continued without any sign of recurrence....Conclusion This is the longest survival under pembrolizumab reported in the literature so far.

While the PD-L1 structural variation we found in this patient with ovarian cancer seems to be a rare event in human tumors with only 31 cases expressing 30 -UTR-truncated PD-L1 transcript out of 10,210 cancer samples from 33 tumor panel analyzed by TCGA reported to date (22), the exquisite sensitivity of this patient to pembrolizumab...Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring PD-L1 gene structural variations causing aberrant PD-L1 expression.