A phase I trial of panobinostat with ipilimumab in advanced melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9547-9547 ◽  
Author(s):  
Nikhil I. Khushalani ◽  
Joseph Markowitz ◽  
Zeynep Eroglu ◽  
Iulia Giuroiu ◽  
Viktoriya Ladanova ◽  
...  
Keyword(s):  
T Cells ◽  
Dose Escalation ◽  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Advanced Melanoma ◽  
Dose Finding ◽  
Biomarker Analysis ◽  
Finding Study ◽  
Tumor Biopsies

9547 Background: Immune checkpoint blockade is standard therapy for advanced melanoma (MEL), yet not all patients (pts) benefit. Panobinostat (PAN), a pan inhibitor of class I, II, and IV histone deacetylases (HDAC) is immunomodulatory, decreases tumor associated inhibitory cytokines and inhibition of effector T-cells. This dose finding study aimed to determine the safety and efficacy of escalating doses of PAN combined with ipilimumab (IPI) in advanced MEL. Methods: Eligible pts with unresectable stage 3/4 MEL, up to 3 prior lines of therapy, and adequate laboratory values were treated with oral PAN 5mg thrice weekly (TIW) plus IPI at 3mg/kg IV every 3 weeks X 4 doses, followed by maintenance PAN until progression or intolerance. Using a modified Ji design, PAN dose escalation by 5mg was planned in 3-12 pt cohorts up to a maximum dose of 20mg TIW, without intra-pt dose escalation. Dose limiting toxicity (DLT) was assessed up to day 84 from start of therapy. Results: Seventeen pts (M/F: 13/4), median age 66 yrs (48, 80) were treated with a median of 4 cycles of IPI (1,4). Of 6 pts treated at PAN 5mg TIW, there was one DLT (G3 hydronephrosis). Eleven pts received PAN 10mg TIW; of 9 evaluable for DLT, there were 3 DLTs (G3 rash, G3 diarrhea, G4 thrombocytopenia) preventing further dose escalation. Other G3 toxicities included anemia, hypophysitis, diarrhea, fatigue (all n = 2); rash, colitis, nausea, dehydration, dizziness, hypotension, ↑ lipase, ↓ sodium, & ↑ glucose (all n = 1). Three pts had previous anti-PD1 therapy. The response rate was 12% (2 PRs) with 35% stable disease. One pt remains on PAN > 24m since start of therapy. Median progression free- and overall survival was 2.23m (95% CI,1.57, 5.8) and 20.97m (95% CI, 8.97, NR) respectively. Biomarker analysis from peripheral blood and limited tumor biopsies pre-and on treatment examining immunoregulatory markers, including EOMES promoter acetylation in T-cells from PAN are ongoing. Conclusions: At tolerated doses, PAN does not appear to increase response to standard IPI in advanced MEL. Biomarker analyses will inform if immunomodulation by PAM improves efficacy of IPI. Combinations with selective HDAC inhibitors may be more appropriate for future study. Supported by grant P50 CA168536, Moffitt Skin Cancer SPORE. Clinical trial information: NCT02032810.

Pharmacodynamic-guided, modified continuous reassessment method (mCRM)-based, dose finding study of rapamycin in adult patients with solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3020-3020 ◽  
Author(s):  
A. Jimeno ◽  
P. Kulesza ◽  
G. Cusatis ◽  
A. Howard ◽  
Y. Khan ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Level ◽  
Dose Escalation ◽  
Dose Finding ◽  
Phase I Trials ◽  
Dose Selection ◽  
Normal Tissues ◽  
Tumor Biopsies ◽  
Dose Levels

3020 Background: Pharmacodynamic (PD) studies, using either surrogate or tumor tissues, are frequently incorporated in Phase I trials. However, it has been less common to base dose selection, the primary endpoint in Phase I trials, in PD effects. We conducted a PD-based dose selection study with rapamycin (Rap). Methods: We used the modified continuous reassessment method (mCRM), a computer-based dose escalation algorithm, and adapted the logit function from its classic toxicity-based input data to a PD-based input. We coupled this design to a Phase I trial of Rap with 2 parts: a dose estimation phase where PD endpoints are measured in normal tissues and a confirmation phase where tumor tissue is assessed. Patients (pts) had solid tumors refractory to standard therapy. Rap was given starting at 2 mg/day continuously in 3-pt cohorts. The PD endpoint was pP70S6K in skin and tumor. Biopsies were done on days 0 and 28 of cycle 1, and a PD effect was defined as ≥ 80% inhibition from baseline. The first 2 dose levels (2 and 3 mgs) were evaluated before implementing the mCRM. The data was then fed to the computer that based on the PD effect calculated the next dose level. The mCRM was set so escalation continued until a dose level elicited a PD effect and the mCRM assigned the same dose to 8 consecutive pts, at which point the effect of that dose will be confirmed in tumor biopsies. Other correlates were PET-CT and pharmacokinetics. Results: Ten pts were enrolled at doses of 2 mg (n = 4), 3 mg (n = 3) and 6 mg (n = 3). Toxicity was anemia (4 G1, 1 G2), leucopenia (1 G1, 2 G2), low ANC (2 G2), hyperglycemia (2 G1, 1 G2), hyperlipidemia (4 G1), and mucositis (1 G1, 1 G2). PD responses were seen in 2 and 1 pt at 2 and 3 mg dose levels. Input of data to the mCRM selected a dose of 6 mg for the third cohort, where PD effect was seen in 1 pt, and thus a fourth dose around 9 mg will be tested. No responses by RECIST occurred, but 2 pts had a response by PET. The PK was consistent with prior data (t1/2 24.6 ± 10.2 h, CL 31.4 ± 12.0 L/h, vol of distribution 235 ± 65 L), and exposure increased with dose. Steady-state concentration were in the 5–20 nM range. Conclusions: mCRM-based dose escalation based on real-time PD assessment is feasible and permits the exploitation of PD effects for dose selection in a rational manner. No significant financial relationships to disclose.

scholarly journals Targeting Histone Deacetylases to Modulate Graft-Versus-Host Disease and Graft-Versus-Leukemia

2020 ◽  
Vol 21 (12) ◽  
pp. 4281
Author(s):  
Sena Kim ◽  
Srikanth Santhanam ◽  
Sora Lim ◽  
Jaebok Choi
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Histone Deacetylases ◽  
Therapeutic Strategy ◽  
Hdac Inhibitors ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Therapeutic Benefits ◽  
Graft Versus Leukemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main therapeutic strategy for patients with both malignant and nonmalignant disorders. The therapeutic benefits of allo-HSCT in malignant disorders are primarily derived from the graft-versus-leukemia (GvL) effect, in which T cells in the donor graft recognize and eradicate residual malignant cells. However, the same donor T cells can also recognize normal host tissues as foreign, leading to the development of graft-versus-host disease (GvHD), which is difficult to separate from GvL and is the most frequent and serious complication following allo-HSCT. Inhibition of donor T cell toxicity helps in reducing GvHD but also restricts GvL activity. Therefore, developing a novel therapeutic strategy that selectively suppresses GvHD without affecting GvL is essential. Recent studies have shown that inhibition of histone deacetylases (HDACs) not only inhibits the growth of tumor cells but also regulates the cytotoxic activity of T cells. Here, we compile the known therapeutic potential of HDAC inhibitors in preventing several stages of GvHD pathogenesis. Furthermore, we will also review the current clinical features of HDAC inhibitors in preventing and treating GvHD as well as maintaining GvL.

scholarly journals Immunomodulation in Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3340
Author(s):  
Mithunah Krishnamoorthy ◽  
John G. Lenehan ◽  
Jeremy P. Burton ◽  
Saman Maleki Vareki
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Tumor Immunity ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Cells ◽  
Immune Checkpoint Blockade ◽  
Cancer Treatments ◽  
Immunological Mechanisms ◽  
Tumor Biopsies

Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.

scholarly journals A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression

2009 ◽  
Vol 83 (10) ◽  
pp. 4749-4756 ◽  
Author(s):  
Kara S. Keedy ◽  
Nancie M. Archin ◽  
Adam T. Gates ◽  
Amy Espeseth ◽  
Daria J. Hazuda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Silencing of the integrated human immunodeficiency virus type 1 (HIV-1) genome in resting CD4+ T cells is a significant contributor to the persistence of infection, allowing the virus to evade both immune detection and pharmaceutical attack. Nonselective histone deacetylase (HDAC) inhibitors are capable of inducing expression of quiescent HIV-1 in latently infected cells. However, potent global HDAC inhibition can induce host toxicity. To determine the specific HDACs that regulate HIV-1 transcription, we evaluated HDAC1 to HDAC11 RNA expression and protein expression and compartmentalization in the resting CD4+ T cells of HIV-1-positive, aviremic patients. HDAC1, -3, and -7 had the highest mRNA expression levels in these cells. Although all HDACs were detected in resting CD4+ T cells by Western blot analysis, HDAC5, -8, and -11 were primarily sequestered in the cytoplasm. Using chromatin immunoprecipitation assays, we detected HDAC1, -2, and -3 at the HIV-1 promoter in Jurkat J89GFP cells. Targeted inhibition of HDACs by small interfering RNA demonstrated that HDAC2 and HDAC3 contribute to repression of HIV-1 long terminal repeat expression in the HeLa P4/R5 cell line model of latency. Together, these results suggest that HDAC inhibitors specific for a limited number of class I HDACs may offer a targeted approach to the disruption of persistent HIV-1 infection.

Expand: a Phase 1b, Open-Label, Dose-Finding Study of Ruxolitinib in Patients with Myelofibrosis and Baseline Platelet Counts Between 50 × 109/L and 99 × 109/L

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 177-177 ◽  
Author(s):  
Claire N Harrison ◽  
Heinz Gisslinger ◽  
Carole B. Miller ◽  
Jean-Jacques Kiladjian ◽  
Edric Atienza ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Dose Escalation ◽  
Research Funding ◽  
Dose Finding ◽  
Open Label ◽  
Advisory Committees ◽  
Starting Dose ◽  
Finding Study ◽  
Label Dose ◽  
Phase 1B

Abstract Abstract 177 Background: Ruxolitinib (rux) is a potent oral JAK1 and JAK2 inhibitor that has demonstrated superiority over traditional therapies for the treatment of myelofibrosis (MF). In the two phase 3 COMFORT studies, rux demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life. Although there has been considerable experience in patients (pts) who developed thrombocytopenia in the COMFORT studies, there has been limited experience in pts with baseline thrombocytopenia as those with platelet counts (PLTs) < 100 × 109/L were excluded. The aims of EXPAND are to evaluate the safety of rux and to establish the maximum safe starting dose (MSSD) in thrombocytopenic MF pts. Methods: Phase 1b, open-label, dose-finding study (NCT01317875) in pts with PMF, PPV-MF, or PET-MF and baseline PLTs 50–99 × 109/L. A Bayesian logistic regression model will be used to guide dose-escalation decisions; intra-pt dose modification is allowed during the study. The study consists of 2 phases: dose escalation and safety expansion. Starting dose of rux is 5 mg bid with a maximum of 15 mg bid. In the dose-escalation phase, cohorts will be: 5 mg bid, 5 mg AM/10 mg PM, 10 mg bid, 10 mg AM/15 mg PM, and 15 mg bid. Pts are assigned to 1 of 2 strata based on their baseline PLTs: stratum 1, 75–99 × 109/L; stratum 2, 50–74 × 109/L. Each dose level in the second stratum will be open only if both that dose and the following one are deemed safe in the first stratum. In the safety-expansion phase, 20 additional pts (10 in each stratum) will be treated at the respective MSSD for their stratum. Results: 14 pts (PMF, n = 10; PPV-MF, n = 3; PET-MF, n = 1) have been enrolled in 4 cohorts: 4 pts in stratum 1/cohort 1 (5 mg bid), 3 in stratum 1/cohort 2 (5 mg AM/10 mg PM), 4 in stratum 1/cohort 3 (10 mg bid), and 3 in stratum 2/cohort 1 (5 mg bid). At baseline, all pts had an ECOG performance status of 0–2, and spleen length ranged from 5–30 cm below the costal margin. 12 pts have completed > 28 days of treatment and are evaluable. 2 pts were nonevaluable: 1 pt discontinued at day 6 due to granulocytic sarcoma, and 1 pt took an incorrect dosage from day 1 to 7 but treatment is ongoing. Reported adverse events (AEs) were similar to those previously seen with rux. 7 pts experienced grade 3/4 AEs (only 2 anemia events were study-drug related), and 4 pts experienced serious AEs (Table). The majority of hemoglobin and absolute neutrophil count (ANC) abnormalities were grade 1 or 2. No pt had a grade 4 decrease in PLTs or ANC; 2 pts experienced a grade 4 decrease in hemoglobin. No pt discontinued due to anemia, neutropenia, or thrombocytopenia. No hemorrhagic events were observed. The lowest PLTs across all pts ranged from 29–96 × 109/L. No dose-limiting toxicities (DLTs) were observed. Reductions in spleen length were reported for all 12 evaluable pts and 1 ongoing nonevaluable pt. Splenomegaly completely resolved in 3 pts. Spleen length reductions were rapid and occurred within the first few weeks of therapy. Conclusions: In this study, no DLT has occurred with the first 3 dose levels in pts with PLTs 75–99 × 109/L or with the first dose level in pts with PLTs 50–74 × 109/L. Rux was generally well tolerated, similar to results reported in previous studies, and no pt has discontinued because of thrombocytopenia. The study is ongoing, and additional pts are being recruited for both strata. Pts are receiving dose levels approaching those approved for nonthrombocytopenic MF pts. Disclosures: Harrison: Novartis: Honoraria, Research Funding, Speakers Bureau; YM Bioscience: Consultancy, Honoraria; Sanofi Aventis: Honoraria; Shire: Honoraria, Research Funding. Gisslinger:Novartis: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; AOP Orphan Pharmaceuticals AG: Consultancy, Speakers Bureau. Miller:Novartis: Consultancy, Research Funding, Speakers Bureau, development of educational presentations Other; Incyte: development of educational presentations, development of educational presentations Other. Kiladjian:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shire: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Atienza:Novartis Pharmaceuticals Corporation: Employment. Stalbovskaya:Novartis Pharma AG: Employment, Equity Ownership. Sirulnik:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Al-Ali:Sanofi Aventis: Consultancy, Honoraria; Celgene: Honoraria, Research Funding; Novartis: Consultancy, Honoraria. McMullin:Novartis: Honoraria; Bristol-Myers Squibb: Honoraria; Shire: Honoraria. Verstovsek:Incyte Corporation: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees.

A phase Ib, open-label, dose-finding study of ruxolitinib in patients (pts) with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF), or post-essential thrombocythemia-myelofibrosis (PET-MF) and baseline platelets (PLTs) 50 to <100 x 109/l.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS6642-TPS6642 ◽  
Author(s):  
Heinz Gisslinger ◽  
Mary Frances McMullin ◽  
Nadja Jaekel ◽  
Carole Brennan Miller ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Primary Myelofibrosis ◽  
Dose Finding ◽  
Open Label ◽  
Phase 3 ◽  
Starting Dose ◽  
Finding Study ◽  
Label Dose ◽  
Dose Finding Study ◽  
Pm 10

TPS6642^ Background: Ruxolitinib, a potent and selective oral JAK1/2 inhibitor, has demonstrated rapid and durable reductions in splenomegaly and improved MF-related symptoms and quality of life in 2 phase 3 studies in pts with PMF, PPV-MF, or PET-MF. There is considerable experience in pts who develop thrombocytopenia on study, and ruxolitinib is well-tolerated with dose adjustment. However, there is limited experience in pts with baseline thrombocytopenia as those with low PLTs (< 100 x 109/L) were excluded from the phase 3 protocols. EXPAND (Evaluating RuXolitinib in Patients with Low Baseline PlAtelet CouNts Diagnosed With Myelofibrosis) will evaluate the safety of ruxolitinib and establish the maximum safe starting dose (MSSD) in thrombocytopenic pts with MF. Methods: This is a phase 1b, open-label, dose-finding study (NCT01317875) in pts with PMF, PPV-MF, or PET-MF and baseline PLT 50-100 x 109/L. A Bayesian logistic regression model with escalation with overdose control will be used to guide dose-escalation decisions. The study consists of 2 phases: dose-escalation and safety-expansion. The starting dose is ruxolitinib 5 mg twice daily (BID) with a maximum of 15 mg BID. In the dose-escalation phase, cohorts will be: 5 mg BID, 5 mg am/10 mg pm, 10 mg BID, 10 mg am/15 mg pm, and 15 mg BID; only pts with PLT 75-100 x 109/L (1st stratum) will initially be enrolled. Once safety is established at the first 2 dose levels (5 mg BID; 5 mg am/10 mg pm), pts with PLT 50-75 x 109/L will be included (2nd stratum). Each dose level in the 2nd stratum will be open only if both that dose and the following one are deemed safe in the 1st stratum. In the safety-expansion phase, 20 pts (10 from each stratum) additional to those treated at the MSSD during dose escalation will be treated at the respective MSSD for their stratum. In cohort 1 (n = 4), 3 pts were evaluable as they completed > 28 days of treatment; 1/4 pts discontinued after 6 doses due to disease progression. No dose-limiting toxicities were observed. The second cohort (5 mg am/10 mg pm) has completed enrollment (n = 3) and is ongoing.

Dose-escalation trial of the ALK, MET & ROS1 inhibitor, crizotinib, in patients with advanced cancer

2020 ◽  
Vol 16 (1) ◽  
pp. 4289-4301 ◽  
Author(s):  
Jeffrey W Clark ◽  
D Ross Camidge ◽  
Eunice L Kwak ◽  
Robert G Maki ◽  
Geoffrey I Shapiro ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Daily Maximum ◽  
Human Dose ◽  
Solid Malignancies ◽  
Finding Study ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Favorable Safety

Aim: This first-in-human, dose-finding study evaluated safety, pharmacokinetics and pharmacodynamics of crizotinib and established a recommended Phase II dose (RP2D) among patients with advanced solid malignancies. Patients & methods: Patients received oral crizotinib in a 3 + 3 dose escalation design. Results: Thirty-six patients received crizotinib (50 mg once daily–300 mg twice daily); maximum tolerated dose (and RP2D) was 250 mg twice daily. Most patients (89%) experienced ≥1 treatment-related adverse event. Three patients had grade 3 dose-limiting toxicities: alanine aminotransferase increased (n = 1) and fatigue (n = 2). Generally, an increase in soluble MET was found with increasing crizotinib concentrations. Conclusion: Crizotinib demonstrated a favorable safety profile. The observed pharmacodynamic effect on soluble MET provide evidence for targeted MET inhibition by crizotinib. Clinicaltrials. gov identifier: NCT00585195

801 PRIME™ IL-15 (RPTR-147): Preliminary clinical results and biomarker analysis from a first-in-human Phase 1 study of IL-15 loaded peripherally-derived autologous T cell therapy in solid tumor patients

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A850-A850
Author(s):  
Erika Hamilton ◽  
Sarah Nikiforow ◽  
Philip Bardwell ◽  
Christine McInnis ◽  
Jeffrey Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Metastatic Disease ◽  
Cd8 T Cells ◽  
Dose Escalation ◽  
Phase 1 ◽  
T Cell Clones ◽  
Cell Product ◽  
Cell Clones ◽  
Biomarker Analysis

BackgroundRPTR-147 is a novel autologous non-genetically modified multi-clonal T cell product loaded with an IL15-Fc nanogel. The product was derived from rare peripherally-derived anti-tumor T cell clones that were primed against a multi-antigen cassette containing tumor associated antigens (TAA), known to be over-expressed in specific tumor types. We describe preliminary results from the ongoing first-in-human Phase 1 trial.MethodsAutologous anti-TAA T cells are generated with a proprietary dendritic cell priming process and then loaded with an IL15-Fc nanogel. TAAs used in cassette: PRAME, NY-ESO-1, SSX2, Survivin and WT1. Thawed RPTR-147 is delivered by infusion. Pre- and post-treatment biopsies were collected for biomarker analysis by immunohistochemistry (IHC) and transcriptome sequencing. Serial blood collections were obtained for measuring IL-15 pharmacokinetics and pharmacodynamic parameters including plasma cytokine levels and immunophenotyping by flow cytometry. T cell receptor sequencing (TCRSeq) was used to characterize the T cell repertoire from manufactured T cell product and the patient‘s blood.ResultsInterim clinical and biomarker data from 17 patients with advanced metastatic disease refractory to SOC who received monthly infusions of 20-360 million cells/m², were reviewed (table 1). There were no dose-limiting toxicities and no evidence of cytokine-release syndrome. The 360M/m² dose contained 3X more IL15-Fc than the MTD of systemically administered IL15-Fc,1 but produced less than a tenth of the systemic exposure to free IL15-Fc. Currently, 360M cells/m² is considered safe and well-tolerated. Further dose escalation is planned.Matched evaluable biopsies were obtained in 7 patients. Tumor-infiltrating T cell lymphocytes was observed in 5 cases for CD8 T cells and 4 cases for CD4 T cells. A dose dependent increase in both inflammatory cytokines and NK & CD8+ T cells was observed, consistent with expected MOA and PK. TCRSeq analysis demonstrated that product specific T cell clones could be tracked in both patient‘s blood and tumor over time. Further analysis to decode the specificity of those cells and demonstrate that tumor antigen specific T cells can be found in patient‘s blood and tumor biopsies is ongoing.Of the 17 patients who received RPTR-147 infusions 10 were noted to have stable disease (SD) and in 4 patients SD lasted > 6 months.Abstract 801 Table 1Summary of PatientsTumor types for the 17 patients with advanced metastatic disease included in this clinical trial (NCT0381568)ConclusionsInterim results with RPTR-147 have shown it to be well-tolerated and have a favorable safety profile. Dose-escalation is proceeding. Ongoing biomarker analysis will inform future clinical strategies in matching patients to an optimized PRIME IL-15 T cell product.Trial RegistrationNCT03815682Ethics ApprovalThe study was approved by local institutional IRBs after acceptance of the IND by the FDA.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferenceRomee R, Cooley S, Berrien-Elliott MM, et al. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood 2018;131(23):2515-2527.

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