The Experts below are selected from a list of 27 Experts worldwide ranked by ideXlab platform
Robert H Pierce - One of the best experts on this subject based on the ideXlab platform.
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intratumoral plasmid il12 expands cd8 t cells and induces a cxcr3 gene signature in triple negative breast tumors that sensitizes patients to anti pd 1 therapy
Clinical Cancer Research, 2021Co-Authors: Melinda L Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R Acharya, Kaitlin Zablotsky, Bernard A Fox, Carlo Bifulco, Shawn M Jensen, Carmen Ballesterosmerino, Robert H PierceAbstract:Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed. Patients and Methods: Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (Tavokinogene Telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets. Results: Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response. Conclusions: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
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phase ii trial of il 12 plasmid transfection and pd 1 blockade in immunologically quiescent melanoma
Clinical Cancer Research, 2020Co-Authors: Alain Patrick Algazi, Christopher G Twitty, Katy K Tsai, Robert H Pierce, Erica Browning, Reneta Hermiz, David A Canton, Donna Bannavong, Arielle Oglesby, Murray FranciscoAbstract:Purpose: Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (Tavokinogene Telseplasmid; “tavo”) electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL). Patients and Methods: Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done. Results: The combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses. Conclusions: The combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors.
Melinda L Telli - One of the best experts on this subject based on the ideXlab platform.
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intratumoral plasmid il12 expands cd8 t cells and induces a cxcr3 gene signature in triple negative breast tumors that sensitizes patients to anti pd 1 therapy
Clinical Cancer Research, 2021Co-Authors: Melinda L Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R Acharya, Kaitlin Zablotsky, Bernard A Fox, Carlo Bifulco, Shawn M Jensen, Carmen Ballesterosmerino, Robert H PierceAbstract:Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed. Patients and Methods: Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (Tavokinogene Telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets. Results: Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response. Conclusions: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
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abstract ct022 intratumoral plasmid il 12 and electroporation in pre treated inoperable locally advanced or recurrent triple negative breast cancer tnbc
Cancer Research, 2018Co-Authors: Melinda L Telli, Christopher G Twitty, Kaitlin Zablotsky, Sharron Gargosky, Irene L WapnirAbstract:Introduction: TNBC accounts for ~15% of breast cancer and is associated with an increased risk of relapse. Emerging data suggest that some TNBC patients benefit from therapies targeting PD-1/PD-L1, but success is limited when patients are heavily pre-treated and lack immunogenic tumors. We designed a protocol to determine whether intratumoral plasmid IL-12 (Tavokinogene Telseplasmid; tavo) with electroporation (IT-tavo-EP) of inoperable locally advanced or recurrent TNBC would elicit a pro-inflammatory molecular and histological signature in treated as well untreated sites. This gene therapy forces intratumoral expression of the proinflammatory cytokine IL-12 enabling conversion of poorly-immunogenic/low T cell infiltrating tumors into highly inflamed immunologically active lesions. Methods: Eligible patients had pre-treated TNBC and at least 2 anatomically distinct cutaneous or subcutaneous lesions accessible for injection and electroporation, with or without other regional or distant metastases. 10 patients were planned for enrollment. IT-tavo-EP was administered on Days 1, 5 and 8 of a single 28-day cycle. Tavo was injected intratumorally (based on tumor volume) at a concentration of 0.5 mg/mL and immediately followed by co-localized electroporation (6 pulses at 1500 V/cm with 1-second intervals). Tumor biopsies were obtained at baseline and post-treatment on day 28 of both treated and untreated lesions. TILs, IL-12 expression, and markers of immunologic phenotype by multiparametric IHC and gene expression were assessed. Lesions were measured with calipers pre- and post-treatment. Adverse events and procedure-related pain were recorded. Results: At the time of abstract submission, 5 patients have completed all study-related procedures and have complete correlative data available. Tavo dose delivered per patient per day ranged from 1.36 to 20 mL. Reported treatment-related adverse events included transient pain associated with electroporation (grade 1) and fatigue (grade 1). Max pain scores (range 0-10) were recorded as an average of 1, with a single patient reporting a 5 at 5 min post-treatment. Treatment-related increase in CD8+ TIL density was observed by intratumoral chromogenic staining (3% at baseline, 11% on day 28 in treated tumors and 5% on day 28 in untreated tumors). Two patients with treatment refractory TNBC received nivolumab as their immediate next therapy and experienced clinically meaningful objective responses. Updated data will be presented. Conclusions: The present study suggests IT-tavo-EP is a safe and tolerable TIL stimulating therapy of skin and subcutaneous triple-negative tumors. Further study of this therapy in combination with anti-PD-1/PD-L1 antibody therapy is warranted. Citation Format: Melinda L. Telli, Kaitlin Zablotsky, Sharron E. Gargosky, Christopher G. Twitty, Irene L. Wapnir. Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT022.
Haydon Andrew - One of the best experts on this subject based on the ideXlab platform.
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799 Durable responses and immune activation with intratumoral electroporation of pIL-12 plus pembrolizumab in actively progressing anti-PD-1 refractory advanced melanoma: KEYNOTE 695 interim data
Providence St. Joseph Health Digital Commons, 2020Co-Authors: Fernandez-penas Pablo, Carlino Matteo, Tsai Katy, Atkinson Victoria, Shaheen Monaster, Thomas Sajeve, Mihalcioiu Catalin, Van Hagen Tom, Roberts-thomson Rachel, Haydon AndrewAbstract:Background Electroporated plasmid IL-12 (TAVO or Tavokinogene Telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1.1 2 Interim data from patients with stage III/IV melanoma actively progressing on anti-PD-1 antibody are presented herein. Methods Patients with confirmed disease progression by RECIST v1.1 after at least 12 weeks of treatment on pembrolizumab or nivolumab (or combination checkpoint blockade) and within 12 weeks of last dose (with no intervening therapies) were enrolled. There was no limit on the number of prior lines of therapy. At least one accessible lesion was electroporated with plasmid IL-12 (pIL-12-EP) on days 1, 5 and 8 every 6 weeks and pembrolizumab was administered every 3 weeks. Tumor response in treated and untreated lesions was assessed by RECIST v1.1 every 12 weeks. Endpoints include ORR, safety, PFS, OS, and DOR. Results The first 56 patients treated of 100 planned were included in this interim analysis. Of these, 84% had Stage IV disease, 30% had M1c or M1d disease, and 27% had prior exposure to ipilimumab. In 54 efficacy evaluable patients the investigator-assessed ORR was 30% (3 CR/13 PR), 5 patients had 100% reduction of target lesions. All responses have been confirmed, only two responding patient progressed while on study, 2 patients completed the study with ongoing responses (figures 1 and 2). In patients with M1c/M1d disease, the ORR was 35.2% (n=6/17). Tumor reduction was observed in untreated lesions in 12 of 12 patients who had unaccessible lesions or accessible untreated lesions. The median overall survival (mOS) and duration of response (mDOR) has not been reached, with a median follow-up time of 13 months. Grade 3 treatment-related adverse events (TRAEs) were seen in 5.4% of patients, and there were no grade 4/5 TRAEs. The rate of grade 3 treatment-emergent (TEAEs) regardless of cause was 23.2%. The median time for pIL-12-EP treatment was 10 minutes (range 2,46). Consistent with prior studies of single-agent pIL-12-EP, tumor IHC, and transcriptomic assessments revealed hallmarks of antigen-specific antitumor immunity in this study. Additional analyses including microbiome, TCR clonality, and peripheral blood biomarker assays will be presented. Best confirmed overall response by RECIST v1.1 after confirmed progression on anti PD-1 data-icon-position= data-hide-link-title= 0 \u3e Abstract 799 Figure 1 Best confirmed overall response by RECIST v1.1 after confirmed progression on anti PD-1 Percent change in sum of target lesions over time data-icon-position= data-hide-link-title= 0 \u3e Abstract 799 Figure 2 Percent change in sum of target lesions over time Conclusions In this rigorously defined PD-1 antibody refractory patient population, the addition of pIL-12-EP to PD-1 antibody therapy induced deep, durable, systemic response in local treated and distant visceral metastatic untreated lesions with nominal systemic toxicity. Trial Registration Trial Registration: NCT#03132675 Ethics Approval The study was approved by a central IRB and/or local institutional IRBs/Ethics Committees as required for each participating institution. Consent Written informed consent was obtained from the patients participating within the trial, the current abstract does not contain sensitive or identifiable information requiring an additional consent from patients. References Algazi A, Bhatia S, Agarwala S, et al. Intratumoral delivery of Tavokinogene Telseplasmid yields systemic immune responses in metastatic melanoma patients. Annals of Oncology 2019;31:532–540. Algazi A, Twitty C, Tsai K, et al. Phase II trial for IL-12 plasmid transfection and PD-1 blockade in immunologically quiescent melanoma. Clinical Cancer Research 2020;26:2827-2837. http://dx.doi.org/10.1136/jitc-2020-SITC2020.079
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799 Durable responses and immune activation with intratumoral electroporation of pIL-12 plus pembrolizumab in actively progressing anti-PD-1 refractory advanced melanoma: KEYNOTE 695 interim data
Providence St. Joseph Health Digital Commons, 2020Co-Authors: Fernandez-penas Pablo, Carlino Matteo, Tsai Katy, Atkinson Victoria, Thomas Sajeve, Mihalcioiu Catalin, Roberts-thomson Rachel, Shaheen Monater, Hagen, Tom Van, Haydon AndrewAbstract:Background Electroporated plasmid IL-12 (TAVO or Tavokinogene Telseplasmid) is a novel pro-inflammatory intratumoral therapy with substantial single agent activity in melanoma, which has been shown to synergize with anti-PD-1 antibodies in patients predicted as non-responders to anti-PD-1.1 2 Interim data from patients with stage III/IV melanoma actively progressing on anti-PD-1 antibody are presented herein. Methods Patients with confirmed disease progression by RECIST v1.1 after at least 12 weeks of treatment on pembrolizumab or nivolumab (or combination checkpoint blockade) and within 12 weeks of last dose (with no intervening therapies) were enrolled. There was no limit on the number of prior lines of therapy. At least one accessible lesion was electroporated with plasmid IL-12 (pIL-12-EP) on days 1, 5 and 8 every 6 weeks and pembrolizumab was administered every 3 weeks. Tumor response in treated and untreated lesions was assessed by RECIST v1.1 every 12 weeks. Endpoints include ORR, safety, PFS, OS, and DOR. Results The first 56 patients treated of 100 planned were included in this interim analysis. Of these, 84% had Stage IV disease, 30% had M1c or M1d disease, and 27% had prior exposure to ipilimumab. In 54 efficacy evaluable patients the investigator-assessed ORR was 30% (3 CR/13 PR), 5 patients had 100% reduction of target lesions. All responses have been confirmed, only two responding patient progressed while on study, 2 patients completed the study with ongoing responses (figures 1 and 2). In patients with M1c/M1d disease, the ORR was 35.2% (n=6/17). Tumor reduction was observed in untreated lesions in 12 of 12 patients who had unaccessible lesions or accessible untreated lesions. The median overall survival (mOS) and duration of response (mDOR) has not been reached, with a median follow-up time of 13 months. Grade 3 treatment-related adverse events (TRAEs) were seen in 5.4% of patients, and there were no grade 4/5 TRAEs. The rate of grade 3 treatment-emergent (TEAEs) regardless of cause was 23.2%. The median time for pIL-12-EP treatment was 10 minutes (range 2,46). Consistent with prior studies of single-agent pIL-12-EP, tumor IHC, and transcriptomic assessments revealed hallmarks of antigen-specific antitumor immunity in this study. Additional analyses including microbiome, TCR clonality, and peripheral blood biomarker assays will be presented. Best confirmed overall response by RECIST v1.1 after confirmed progression on anti PD-1 data-icon-position= data-hide-link-title= 0 \u3e Download figure Open in new tab Download powerpoint Abstract 799 Figure 1 Best confirmed overall response by RECIST v1.1 after confirmed progression on anti PD-1 Percent change in sum of target lesions over time data-icon-position= data-hide-link-title= 0 \u3e Download figure Open in new tab Download powerpoint Abstract 799 Figure 2 Percent change in sum of target lesions over time Conclusions In this rigorously defined PD-1 antibody refractory patient population, the addition of pIL-12-EP to PD-1 antibody therapy induced deep, durable, systemic response in local treated and distant visceral metastatic untreated lesions with nominal systemic toxicity. Trial Registration Trial Registration: NCT#0313267
Kaitlin Zablotsky - One of the best experts on this subject based on the ideXlab platform.
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intratumoral plasmid il12 expands cd8 t cells and induces a cxcr3 gene signature in triple negative breast tumors that sensitizes patients to anti pd 1 therapy
Clinical Cancer Research, 2021Co-Authors: Melinda L Telli, Hiroshi Nagata, Irene Wapnir, Chaitanya R Acharya, Kaitlin Zablotsky, Bernard A Fox, Carlo Bifulco, Shawn M Jensen, Carmen Ballesterosmerino, Robert H PierceAbstract:Purpose: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed. Patients and Methods: Using mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (Tavokinogene Telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets. Results: Single-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti–PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti–PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response. Conclusions: These data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.
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abstract ct022 intratumoral plasmid il 12 and electroporation in pre treated inoperable locally advanced or recurrent triple negative breast cancer tnbc
Cancer Research, 2018Co-Authors: Melinda L Telli, Christopher G Twitty, Kaitlin Zablotsky, Sharron Gargosky, Irene L WapnirAbstract:Introduction: TNBC accounts for ~15% of breast cancer and is associated with an increased risk of relapse. Emerging data suggest that some TNBC patients benefit from therapies targeting PD-1/PD-L1, but success is limited when patients are heavily pre-treated and lack immunogenic tumors. We designed a protocol to determine whether intratumoral plasmid IL-12 (Tavokinogene Telseplasmid; tavo) with electroporation (IT-tavo-EP) of inoperable locally advanced or recurrent TNBC would elicit a pro-inflammatory molecular and histological signature in treated as well untreated sites. This gene therapy forces intratumoral expression of the proinflammatory cytokine IL-12 enabling conversion of poorly-immunogenic/low T cell infiltrating tumors into highly inflamed immunologically active lesions. Methods: Eligible patients had pre-treated TNBC and at least 2 anatomically distinct cutaneous or subcutaneous lesions accessible for injection and electroporation, with or without other regional or distant metastases. 10 patients were planned for enrollment. IT-tavo-EP was administered on Days 1, 5 and 8 of a single 28-day cycle. Tavo was injected intratumorally (based on tumor volume) at a concentration of 0.5 mg/mL and immediately followed by co-localized electroporation (6 pulses at 1500 V/cm with 1-second intervals). Tumor biopsies were obtained at baseline and post-treatment on day 28 of both treated and untreated lesions. TILs, IL-12 expression, and markers of immunologic phenotype by multiparametric IHC and gene expression were assessed. Lesions were measured with calipers pre- and post-treatment. Adverse events and procedure-related pain were recorded. Results: At the time of abstract submission, 5 patients have completed all study-related procedures and have complete correlative data available. Tavo dose delivered per patient per day ranged from 1.36 to 20 mL. Reported treatment-related adverse events included transient pain associated with electroporation (grade 1) and fatigue (grade 1). Max pain scores (range 0-10) were recorded as an average of 1, with a single patient reporting a 5 at 5 min post-treatment. Treatment-related increase in CD8+ TIL density was observed by intratumoral chromogenic staining (3% at baseline, 11% on day 28 in treated tumors and 5% on day 28 in untreated tumors). Two patients with treatment refractory TNBC received nivolumab as their immediate next therapy and experienced clinically meaningful objective responses. Updated data will be presented. Conclusions: The present study suggests IT-tavo-EP is a safe and tolerable TIL stimulating therapy of skin and subcutaneous triple-negative tumors. Further study of this therapy in combination with anti-PD-1/PD-L1 antibody therapy is warranted. Citation Format: Melinda L. Telli, Kaitlin Zablotsky, Sharron E. Gargosky, Christopher G. Twitty, Irene L. Wapnir. Intratumoral plasmid IL-12 and electroporation in pre-treated inoperable locally advanced or recurrent triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT022.
Murray Francisco - One of the best experts on this subject based on the ideXlab platform.
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phase ii trial of il 12 plasmid transfection and pd 1 blockade in immunologically quiescent melanoma
Clinical Cancer Research, 2020Co-Authors: Alain Patrick Algazi, Christopher G Twitty, Katy K Tsai, Robert H Pierce, Erica Browning, Reneta Hermiz, David A Canton, Donna Bannavong, Arielle Oglesby, Murray FranciscoAbstract:Purpose: Tumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (Tavokinogene Telseplasmid; “tavo”) electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL). Patients and Methods: Tavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done. Results: The combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses. Conclusions: The combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors.
