FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4220857519> ?p ?o ?g. }

• W4220857519 endingPage "e38" @default.
• W4220857519 startingPage "e37" @default.
• W4220857519 abstract "Purpose/Objective(s) Persistent HPV16 DNA infection is associated with up to 70% of OPSCC and recurrent/metastatic disease is often incurable and poorly palliated by standard therapies. Despite significant advances documented with checkpoint inhibitor (CPI) immunotherapy, clinical benefit and efficacy remains limited in most patients due to a lack of meaningful tumor-directed T cell responses. Major barriers to effective cancer vaccine delivery include a relative absence of shared neo-antigens between tumors and weak T-cell activation. PDS0101 is a T-cell activating immunotherapy directed against preserved HPV neoantigens E6/7 that is based on a cationic lipid nanoparticle platform that promotes antigen processing and cross presentation. It has been shown to specifically upregulate type I interferons, allowing generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells in vivo as well as immune memory. VERSATILE-002 (NCT04260126) is a phase 2 study of the combination of PDS0101 and pembrolizumab in first line treatment (CPI naïve) and CPI refractory patients with recurrent or metastatic HPV16-related OPSCC. Herein, we report preliminary safety data for CPI naïve patients. Materials/Methods Subjects are treated with pembrolizumab 200mg IV every three weeks plus SC PDS0101 following pembrolizumab on days one of C1-4 and C12. An initial safety cohort was assessed during Cycle 1 and 21 days following, for dose limiting toxicity (DLT) and thereafter for safety and tolerability of the combination. Results Fifteen CPI naïve subjects, median age 60 yrs (range 46-68), all male, 14 (93%) of whom were White and not Hispanic or Latino, received at least one cycle of combination therapy. All were confirmed HPV16 postive and to have a CPS score >=1 (8 with CPS >=20); 8 (53%) were ECOG 0 and 93% had received prior curative intent HNSCC therapy. At the time of safety review, subjects had received a median of 4 doses (range 1-4) of PDS0101 and pembrolizumab. Treatment-emergent adverse events (TEAEs) were documented in 9 (60%) subjects: self-limited, Grade 1 local inject site reactions predominated (7 subjects, 47%), with occasional ≤ Gr2 fatigue, nausea or diarrhea (13% of subjects or fewer). Five subjects had serious adverse events (SAEs), all unrelated to PDS0101 and pembrolizumab. No DLTs, drug discontinuation related to toxicity or immune-related AEs have been documented to date. Conclusion The combination of PDS0101 and pembrolizumab is safe and well tolerated without evidence of enhanced or significant toxicity. Persistent HPV16 DNA infection is associated with up to 70% of OPSCC and recurrent/metastatic disease is often incurable and poorly palliated by standard therapies. Despite significant advances documented with checkpoint inhibitor (CPI) immunotherapy, clinical benefit and efficacy remains limited in most patients due to a lack of meaningful tumor-directed T cell responses. Major barriers to effective cancer vaccine delivery include a relative absence of shared neo-antigens between tumors and weak T-cell activation. PDS0101 is a T-cell activating immunotherapy directed against preserved HPV neoantigens E6/7 that is based on a cationic lipid nanoparticle platform that promotes antigen processing and cross presentation. It has been shown to specifically upregulate type I interferons, allowing generation of high levels of polyfunctional HPV16-specific CD8 and CD4 T cells in vivo as well as immune memory. VERSATILE-002 (NCT04260126) is a phase 2 study of the combination of PDS0101 and pembrolizumab in first line treatment (CPI naïve) and CPI refractory patients with recurrent or metastatic HPV16-related OPSCC. Herein, we report preliminary safety data for CPI naïve patients. Subjects are treated with pembrolizumab 200mg IV every three weeks plus SC PDS0101 following pembrolizumab on days one of C1-4 and C12. An initial safety cohort was assessed during Cycle 1 and 21 days following, for dose limiting toxicity (DLT) and thereafter for safety and tolerability of the combination. Fifteen CPI naïve subjects, median age 60 yrs (range 46-68), all male, 14 (93%) of whom were White and not Hispanic or Latino, received at least one cycle of combination therapy. All were confirmed HPV16 postive and to have a CPS score >=1 (8 with CPS >=20); 8 (53%) were ECOG 0 and 93% had received prior curative intent HNSCC therapy. At the time of safety review, subjects had received a median of 4 doses (range 1-4) of PDS0101 and pembrolizumab. Treatment-emergent adverse events (TEAEs) were documented in 9 (60%) subjects: self-limited, Grade 1 local inject site reactions predominated (7 subjects, 47%), with occasional ≤ Gr2 fatigue, nausea or diarrhea (13% of subjects or fewer). Five subjects had serious adverse events (SAEs), all unrelated to PDS0101 and pembrolizumab. No DLTs, drug discontinuation related to toxicity or immune-related AEs have been documented to date. The combination of PDS0101 and pembrolizumab is safe and well tolerated without evidence of enhanced or significant toxicity." @default.
• W4220857519 created "2022-04-03" @default.
• W4220857519 creator A5007743619 @default.
• W4220857519 creator A5010233024 @default.
• W4220857519 creator A5022384270 @default.
• W4220857519 creator A5035283039 @default.
• W4220857519 creator A5055736099 @default.
• W4220857519 creator A5081812286 @default.
• W4220857519 creator A5091639280 @default.
• W4220857519 date "2022-04-01" @default.
• W4220857519 modified "2023-09-27" @default.
• W4220857519 title "Preliminary Safety of PDS0101 (Versamune +HPVmix) and Pembrolizumab Combination Therapy in Subjects with Recurrent/Metastatic Human Papillomavirus-16 Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC)" @default.
• W4220857519 doi "https://doi.org/10.1016/j.ijrobp.2021.12.087" @default.
• W4220857519 hasPublicationYear "2022" @default.
• W4220857519 type Work @default.
• W4220857519 citedByCount "1" @default.
• W4220857519 countsByYear W42208575192023 @default.
• W4220857519 crossrefType "journal-article" @default.
• W4220857519 hasAuthorship W4220857519A5007743619 @default.
• W4220857519 hasAuthorship W4220857519A5010233024 @default.
• W4220857519 hasAuthorship W4220857519A5022384270 @default.
• W4220857519 hasAuthorship W4220857519A5035283039 @default.
• W4220857519 hasAuthorship W4220857519A5055736099 @default.
• W4220857519 hasAuthorship W4220857519A5081812286 @default.
• W4220857519 hasAuthorship W4220857519A5091639280 @default.
• W4220857519 hasConcept C121608353 @default.
• W4220857519 hasConcept C126322002 @default.
• W4220857519 hasConcept C143998085 @default.
• W4220857519 hasConcept C147483822 @default.
• W4220857519 hasConcept C197934379 @default.
• W4220857519 hasConcept C203014093 @default.
• W4220857519 hasConcept C2777701055 @default.
• W4220857519 hasConcept C2778375690 @default.
• W4220857519 hasConcept C2780057760 @default.
• W4220857519 hasConcept C71924100 @default.
• W4220857519 hasConceptScore W4220857519C121608353 @default.
• W4220857519 hasConceptScore W4220857519C126322002 @default.
• W4220857519 hasConceptScore W4220857519C143998085 @default.
• W4220857519 hasConceptScore W4220857519C147483822 @default.
• W4220857519 hasConceptScore W4220857519C197934379 @default.
• W4220857519 hasConceptScore W4220857519C203014093 @default.
• W4220857519 hasConceptScore W4220857519C2777701055 @default.
• W4220857519 hasConceptScore W4220857519C2778375690 @default.
• W4220857519 hasConceptScore W4220857519C2780057760 @default.
• W4220857519 hasConceptScore W4220857519C71924100 @default.
• W4220857519 hasIssue "5" @default.
• W4220857519 hasLocation W42208575191 @default.
• W4220857519 hasOpenAccess W4220857519 @default.
• W4220857519 hasPrimaryLocation W42208575191 @default.
• W4220857519 hasRelatedWork W2342781363 @default.
• W4220857519 hasRelatedWork W2610751918 @default.
• W4220857519 hasRelatedWork W2777867648 @default.
• W4220857519 hasRelatedWork W2786497694 @default.
• W4220857519 hasRelatedWork W2904110710 @default.
• W4220857519 hasRelatedWork W2969782175 @default.
• W4220857519 hasRelatedWork W3153432702 @default.
• W4220857519 hasRelatedWork W3161613553 @default.
• W4220857519 hasRelatedWork W3215044659 @default.
• W4220857519 hasRelatedWork W4309809336 @default.
• W4220857519 hasVolume "112" @default.
• W4220857519 isParatext "false" @default.
• W4220857519 isRetracted "false" @default.
• W4220857519 workType "article" @default.