Validating critical analytical variables of a multiplexed gene expression assay measuring tumor inflammation designed to predict response to anti-PD1 therapy.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 203-203 ◽  
Author(s):  
Simina Popa ◽  
Sarah Elizabeth Church ◽  
Irena Pekker ◽  
Naeem Dowidar ◽  
Amy Sullivan ◽  
...  
Keyword(s):  
Single Agent ◽  
Ffpe Tissue ◽  
Analytical Performance ◽  
Analytical Validation ◽  
Multiple Tumor ◽  
Analytical Precision ◽  
Input Range ◽  
Tumor Inflammation ◽  
Methods Analytical ◽  
Tumor Types

203 Background: The development and analytical performance of the Tumor Inflammation Signature (TIS) assay has been described previously. The TIS is an investigational use RNA expression assay on the nCounter Dx Analysis System, which is being evaluated as a patient enrichment biomarker for treatment with pembrolizumab single agent across multiple solid tumor types. Here we describe the analytical validation of the RNA input range and analytical precision starting from RNA isolated from formalin fixed paraffin embedded (FFPE) tissue blocks. Methods: Analytical validation of TIS assay performance across an RNA input range was performed using samples from 11 tumor types. The analytical precision between sites, instruments, reagent lots, and users was measured, using RNA samples isolated from FFPE tissue blocks. Results: The assay was validated across the specified RNA input range with ≥ 94% concordance at the minimum specified RNA input (50ng). The total standard deviation of the TIS score was < 0.04 units across three sites with ≥98% concordance between sites. The 6 users across the three sites did not significantly contribute to the assay variability. There was 100% concordance in biomarker high/low categorization between multiple reagent lots and multiple instruments. Conclusions: The analytical performance of the NanoString TIS assay has been validated to give consistent results across the RNA input range and between site, instrument, assay user, and reagent kit lot. The assay is well suited for decentralized clinical testing and is currently under investigation as a biomarker to enrich for response to anti-PD1 therapy across multiple tumor types.

Verification of the analytical performance of a molecular diagnostic for response to anti-PD1 therapy on the nCounter Dx Analysis System.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 8-8
Author(s):  
Brett Wallden ◽  
Irena Pekker ◽  
Simina Popa ◽  
Naeem Dowidar ◽  
Celine Ngouenet ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Cross Reactivity ◽  
Analytical Performance ◽  
Molecular Diagnostic ◽  
Clinical Activity ◽  
Gene Probe ◽  
Multiple Tumor ◽  
Input Range ◽  
Tumor Types

8 Background: Pembrolizumab is a humanized anti-PD1 antibody that is approved for use in advanced melanoma, recurrent or metastatic head and neck squamous cell carcinoma, and metastatic non-small-cell lung cancer. It has also shown clinical activity in a number of other tumor types in clinical trials, but there is need for a precise and accurate test that can identify patients most likely to benefit from therapy. We have previously described the development and analytical performance of a NanoString RNA expression clinical trial assay, referred to here as the Tumor Inflammation Signature (TIS) assay, which is being evaluated as a patient enrichment biomarker in multiple solid tumor types for treatment with pembrolizumab. Here we describe additional performance data and analytical verification of reproducibility from tissue and RNA input range in multiple tumor types. Methods: Linearity and specificity were assessed with single targets or pools of in vitro transcribed RNAs with sequences matching the 18 biomarker and 10 normalization gene probe targets. The verification of the previously reported analytical precision from RNA and reproducibility from tissue was performed using independent samples from 11 tumor types. The biological variability of the signature within a patient sample was evaluated by testing multiple core punches from formalin fixed paraffin embedded (FFPE) tissue blocks. Results: The TIS assay’s measurement of the 28 genes was linear across a wide dynamic range ( ≥ 4 logs) and was highly specific with < 1% cross reactivity between probes. The assay was verified across the specified RNA input range with > 90% concordance at the low end (50ng) of the RNA input range. The total standard deviation of the anti-PD1 Predictor Score from tissue was verified as < 5% of the signature score range and > 90% concordance in biomarker high/low categorization within the biological replicates. Conclusions: The analytical performance of the NanoString TIS assay was verified to be robust. The assay is well suited for decentralized clinical testing and is currently under investigation to identify responders to anti-PD1 therapy in multiple tumor types in several clinical studies.

Preclinical efficacy evaluation of ixabepilone (BMS-247550) in combination with cetuximab or capecitabine in human colon and lung carcinoma xenografts

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12017-12017 ◽  
Author(s):  
F. Y. Lee ◽  
A. Camuso ◽  
S. Castenada ◽  
C. Flefleh ◽  
I. Ingio ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Lung Carcinoma ◽  
Therapeutic Potential ◽  
Single Agent ◽  
Human Colon ◽  
Maximum Tolerated Dose ◽  
Antitumor Efficacy ◽  
Efficacy Evaluation ◽  
Multiple Tumor ◽  
Tumor Types

12017 Background: Ixabepilone belongs to a class of structurally novel, microtubule-stabilizing agents that exert their antimitotic action by binding to tubulin with a binding mode that is distinct from the taxanes. Preclinical findings that ixabepilone has antitumor activity in a broad spectrum of tumor types, including taxane-resistant tumors, is borne out by Phase II clinical trials where ixabepilone has demonstrated activities in multiple tumor types including breast, renal, pancreatic, prostate and lymphoma. The aim of this series of studies was to further characterize the therapeutic potential of ixabepilone in combination with currently approved chemotherapy agents. Methods: Antitumor activity was evaluated in the GEO human colon and L2987 human lung carcinoma xenografts. Therapeutic synergism of the combination was defined as the attainment of efficacy that was significantly better than the best response of the individual single agents administered at their maximum-tolerated dose (MTD) or optimal dose (OD). Results: In the GEO tumors, single-agent ixabepilone produced 1.1 log cell kill (LCK) at its MTD. Cetuximab at its OD yielded 0.8 LCK. The combination of ixabepilone and cetuximab produced 1.7 LCK which was significantly superior to ixabepilone alone (P=0.0173) and cetuximab alone (P=0.0002). Similar synergistic efficacy was observed in the L2987 tumors. The combined efficacy of capecitabine plus ixabepilone was evaluated in the GEO tumors. In this tumor, single-agent ixabepilone was modestly active (LCK = 0.8) at its MTD. Single-agent capecitabine was not effective (LCK = 0.4) at its MTD. However, the combination of the two agents produced therapeutic synergism, yielding antitumor efficacy (1.9 LCK) that was superior to either of the agents alone at their MTDs (P=0.035 and 0.0004, respectively). Conclusions: Ixabepilone demonstrates robust synergistic antitumor efficacy when used in combination with cetuximab or capecitabine in human xenografts providing a biologic rationale for these combinations in the treatment of cancer. [Table: see text]

Assessment of safety with abbreviated, weight-based bevacizumab infusions in a variety of solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19674-19674
Author(s):  
J. W. Hart ◽  
J. R. Murillo ◽  
M. S. Oholendt ◽  
H. A. Preti
Keyword(s):  
Solid Tumors ◽  
Single Agent ◽  
Central Nervous System Involvement ◽  
Minimal Risk ◽  
Phase I Clinical Trials ◽  
Multiple Tumor ◽  
Humanized Monoclonal Antibody ◽  
Number Of Patients ◽  
Infusion Schedule ◽  
Tumor Types

19674 Background: Bevacizumab (BEV), a humanized monoclonal antibody that neutralizes vascular endothelial growth factor, has shown improved responses in patients with colorectal cancer (CRC) and non-small cell lung cancer (NSCLC) while displaying activity in a variety of other solid tumors. Phase I clinical trials with BEV utilized standard 90- 60-, and 30-minute infusions for 1st, 2nd, and subsequent infusions, as tolerated; initial doses reported less than 3% incidence of infusion-related adverse events (AEs), with 0.2% grade III/IV reactions. Recommended infusion rates for BEV remain unchanged despite the minimal risk of infusion-related AEs. Saltz and colleagues recently reported novel data supporting the safety and tolerability of abbreviated BEV infusions in CRC patients within a single institution. Our objective was to replicate previously reported safety profiles while utilizing abbreviated infusions of BEV in multiple tumor types. Methods: An internal retrospective analysis revealing minimal infusion AEs with standard infusions facilitated this current study. BEV- naïve and previously-treated patients were consented for the study utilizing the following weight-based infusion times: 5, 10, and 15 mg/kg doses over 10, 20, or 30 minutes, respectively, for all doses. Patients were assessed throughout and immediately following the infusion for any infusion-related AE. Results: A variety of tumor types are represented in 26 enrolled patients including CRC, NSCLC, breast, ovarian, pancreatic, and brain. Central nervous system involvement accounted for 35% of patients [primary brain (23%) and metastatic disease (12%)]. A considerable number of patients (19%) were treated with single-agent BEV. Nine BEV-naïve patients were initiated on abbreviated infusions, while 16 were converted from the standard infusion schedule. Seventy-seven total doses utilizing the abbreviated infusions failed to produce infusion-related AEs. Conclusion: These results support previous data affirming the safety and tolerability of abbreviated BEV infusions in CRC patients, while also reporting promising safety of abbreviated infusions in a variety of additionally unreported solid tumors types. No significant financial relationships to disclose.

Association of LRP1B pathogenic genomic alterations with favorable outcomes with immune checkpoint inhibitors across multiple tumor types.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3007-3007 ◽  
Author(s):  
Landon Carter Brown ◽  
Ramy Sedhom ◽  
Eric B Schwartz ◽  
Jason Zhu ◽  
Chester Kao ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Density Lipoprotein ◽  
Primary Objective ◽  
Missense Mutations ◽  
Multiple Tumor ◽  
Tumor Types

3007 Background: Low-density lipoprotein receptor-related protein 1b (LRP1b) is a putative tumor suppressor and one of the most frequently altered genes in cancer. Our prior single-center work suggested that LRP1B alterations may enrich for responses to immune checkpoint inhibitors (ICI) in solid tumors including prostate cancer; however, validation of these findings is needed. Methods: We conducted a multicenter, retrospective analysis of patients with LRP1B alterations (on tissue-based next-generation sequencing panels) treated with ICI at Duke, Johns Hopkins (JHU), and University of Michigan (UM). The primary objective was to assess the association between objective response rate (ORR) to ICI and pathogenic LRP1B alterations, defined as deletions or truncating alterations, when compared with LRP1B variants of undetermined significance (VUS), defined as missense mutations not predicted to be pathogenic in COSMIC. Missense changes with a COSCMIC FATHMM score of > 0.8 were categorized separately as likely pathogenic. Summary statistics, ORR, progression free survival (PFS), and overall survival (OS) were calculated. Results: 101 patients (44 Duke, 35 JHU, 22 UM) with LRP1B alterations were treated with ICI. Median age was 61 (range 32-82). The most common tumor types by alteration (pathogenic or likely pathogenic/VUS%) were lung (33/47%), GI (17/13%), prostate (11/7%), sarcoma (2/9%), melanoma (11/0%), and others (26/24%). 93% of patients received single-agent PD-(L)1 inhibition. The ORR for patients with either pathogenic/likely pathogenic alterations, or VUS alterations was 57% and 18%, respectively. After excluding MSI-high or TMB-high ( > 10 mut/Mb) tumors, ORR was 14/25 (56%) and 6/36 (17%), respectively. Pathogenic or likely pathogenic LRP1B alterations were associated with longer PFS (HR 0.39, 95% CI 0.24-0.63) and OS (HR 0.58, 95% CI 0.36-0.95). Conclusions: This multicenter study shows impressive and durable objective response rates to ICI for patients harboring pathogenic LRP1B alterations when compared to those with LRP1B VUS, independent of TMB/MSI status. Further mechanistic insights and prospective validation studies are warranted. [Table: see text]

scholarly journals Agnostic Evaluation of Ipilimumab and Nivolumab Association: A Metanalysis.

2020 ◽  
Author(s):  
Paolo Marchetti ◽  
Andrea Botticelli ◽  
Antonio Paolo Ascierto ◽  
Giuseppe Curigliano ◽  
Diana Giannarelli
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Added Value ◽  
Combination Strategy ◽  
Free Survival ◽  
Multiple Tumor ◽  
Single Agent Therapy ◽  
Tumor Types

Abstract Background. Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively, have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintain a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to single agent therapy.Materials and methods. We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results. A total of 8 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumab alone. All trials reported the Objective response rate (ORR) (Table 2), no heterogeneity was found and the pooled Odds Ratio (Figure 1) was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407-2.012; P<0.0001). Three studies were considered for Progression free survival (PFS) analysis (Table 3), no heterogeneity was found and the pooled Hazard Ratio (Figure 2) favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719-0.907; P<0.0001). The Overall survival (OS) endpoint was considered only in 2 trials (Table 4), no heterogeneity was found and the pooled HR (Figure 3) favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763-0.997; P=0.045).Conclusions. The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.

CTNI-55. THE CDK4/6 INHIBITOR ABEMACICLIB IN PATIENTS WITH RECURRENT MENINGIOMA AND OTHER PRIMARY CNS TUMORS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi72-vi73
Author(s):  
Elizabeth Coffee ◽  
Katherine Panageas ◽  
Robert Young ◽  
Tara Morrison ◽  
Ahmad Daher ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Single Agent ◽  
Pituitary Tumors ◽  
Molecular Characteristics ◽  
Multiple Cancer ◽  
Who Grade ◽  
Multiple Tumor ◽  
Primary Brain Tumors ◽  
Basket Trial ◽  
Tumor Types

Abstract BACKGROUND Medical therapies for recurrent brain tumors are limited. Abemaciclib is a small molecule CDK4/6 inhibitor that has demonstrated antitumor activity in multiple cancer types and crosses the blood-brain barrier. METHODS We conducted a phase II trial of single-agent abemaciclib in patients with recurrent primary brain tumors utilizing a novel CNS basket trial design with multiple tumor types accrued to separate cohorts including patients with recurrent IDH-wildtype gliomas (Cohort A), any recurrent gliomas requiring cytoreductive surgery (Cohort B), and any other recurrent primary brain tumors (Cohort C) including IDH-mutant gliomas, meningiomas, and other tumor types. In all patients, abemaciclib was administered orally at 200mg twice daily for each 28-day cycle. In cohort B abemaciclib was administered 4-7 days prior to surgery then resumed after recovery. Neuroimaging disease assessments were performed every two cycles. Cohorts were individually assessed for efficacy, tumoral molecular characteristics, and exploratory biomarker analyses. Next generation sequencing was performed on patients who had prior surgery. RESULTS To date, a total of 61 patients have enrolled and initiated treatment with abemaciclib. Cohort A enrolled 9 patients with IDH-wildtype WHO grade II and III astrocytomas. Cohort B enrolled 10 patients with astrocytomas of varying IDH-status. Cohort C is a diverse group of 42 patients including 22 treatment-refractory meningiomas, 10 IDH-mutant gliomas (5 astrocytomas, 5 oligodendrogliomas), 3 ependymomas, 3 primary CNS lymphomas, 2 pituitary tumors, 1 glioneuronal rosette forming tumor, and 1 diffuse midline glioma. A total of 7 grade 3 toxicities occurred in 6 patients: fatigue (3), neutropenia (2), colitis (1) and seizure (1); no grade 4 toxicities occurred. CONCLUSIONS We present the results of a novel CNS basket trial looking at the efficacy of abemaciclib across multiple recurrent primary brain tumors. Efficacy results will be presented, highlighting an update on promising results in the 22 patients with recurrent meningiomas.

Abstract C168: Cancer-selective mitochondrial copper transport by elesclomol results in potent single agent efficacy in multiple tumor types.

2011 ◽  
Author(s):  
Jim Sang ◽  
Masazumi Nagai ◽  
Chaohua Zhang ◽  
Donald Smith ◽  
Manuel Sequeira ◽  
...  
Keyword(s):  
Single Agent ◽  
Copper Transport ◽  
Multiple Tumor ◽  
Tumor Types

Association of an inflammatory gene signature with CD8 expression by immunohistochemistry (IHC) in multiple tumor types.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2593-2593
Author(s):  
Peter M Szabo ◽  
Zhenhao Qi ◽  
Kim Zerba ◽  
Scott Ely ◽  
Robin Edwards ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Linear Models ◽  
Predictive Accuracy ◽  
Statistical Modelling ◽  
Gene Signature ◽  
Specific Gene ◽  
Multiple Tumor ◽  
Technical Errors ◽  
Tumor Inflammation ◽  
Tumor Types

2593 Background: A multiparameter tumor inflammation assay based on gene expression profiling (TIA-GEP) can extend the utility of IHC to interrogate the tumor microenvironment (TME). Using CD8 expression assessed by IHC (CD8-IHC) as a surrogate for inflammation, statistical modelling was used to develop a specific gene signature on the TIA-GEP panel to predict CD8-IHC. The correlation between TIA-GEP and CD8-IHC and the prevalence of inflammation were explored across multiple tumor types. Methods: Levels of inflammation were measured by CD8-IHC and TIA-GEP on 1778 procured samples across 12 tumor types. Quality control metrics involved sample input quality, technical errors, and inter-run variability. Generalized linear models were used to identify an inflammation score that predicts the CD8-IHC score in melanoma and SCCHN tissue. The predictive accuracy of this signature was also examined in 10 additional tumor types. Results: Assessment of TME inflammation by CD8-IHC was consistent with that observed by TIA-GEP in multiple tumor types. The range of inflammation varied across different tumor types, with relatively lower inflammation range and scores in SCLC, ovarian, and prostate cancers, and higher values in NSCLC, melanoma, SCCHN, and gastric cancers. R2 x 100 values reflecting percent variation in CD8-IHC associated with TIA-GEP ranged from 62.4% to 79.2% ( P < 0.0001) for all tumor types except prostate cancer (32.5%). Low correlation in prostate cancer may be a result of low prevalence of inflammation by CD8-IHC. Estimated linear regression slopes between CD8-IHC and TIA-GEP ranged from 0.74 in SCLC to 1.27 in gastric cancer. Conclusions: The results suggest that the inflammation signature is a robust potential diagnostic tool predicting inflammation in the TME. The inflammation signature not only correlates with CD8-IHC for multiple tumor types, but also leverages the alternative benefits associated with TIA-GEP, which include information related to tumor inflammation-associated biomarkers and flexibility in exploring the value of other genomic signatures.

NKP-1339: Maximum tolerated dose defined for first-in-human GRP78 targeted agent.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3033-3033 ◽  
Author(s):  
Dana Shelton Thompson ◽  
Glen J. Weiss ◽  
Suzanne Fields Jones ◽  
Howard A. Burris ◽  
Ramesh K. Ramanathan ◽  
...  
Keyword(s):  
Phase I ◽  
Single Agent ◽  
Maximum Tolerated Dose ◽  
Unknown Primary ◽  
Multiple Tumor ◽  
Anti Cancer ◽  
Targeted Agent ◽  
Adequate Organ Function ◽  
Tumor Types ◽  
Post Therapy

3033 Background: NKP-1339 is a first-in-class small molecule anti-cancer compound that down-regulates GRP78, a key regulator of misfolded protein processing and tumor survival/anti-apoptosis. GRP78 up-regulation occurs in many tumors, and is associated with intrinsic and chemotherapy-induced resistance. Preclinically, single agent NKP-1339 demonstrates activity against multiple tumor types, including chemoresistant lines. This phase I trial evaluates the safety, tolerability, maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics (PD) of NKP-1339. Methods: Patients (pts) with advanced solid tumors, adequate organ function, ECOG 0-1 are enrolled. NKP-1339 is infused on day 1, 8, and 15 of 28 day cycles. Single pt cohorts are enrolled until grade 2 toxicity, then adjusted to standard 3+3 design. Doses from 20-780 mg/m2 are evaluated. PD samples for plasma GRP78 are collected. At MTD, an expanded cohort of 25 pts is enrolled. Results: 34 pts are enrolled for dose escalation: 30 evaluable for dose determination; 4 replaced due to tumor progression in cycle 1. Demographics: 19M/15F; median age 62 yrs (range 28 to 79). Tumor types: colorectal (CRC, 10), non-small cell lung (NSCLC, 8); neuroendocrine (NET, 5); head and neck (H&N, 3); and other cancer (8). Dose limiting toxicity of grade (gr) 2-3 nausea, with gr 2 creatinine in 1 pt, occurred at 780 mg/m2; MTD is 625 mg/m2. Gr 1 fever/chills is observed above 420 mg/m2, but is prevented by steroid premedication. The most common drug-related events are gr 1 nausea, gr 1-2 vomiting, and gr 1-2 fatigue. No lab abnormalities were noted except reversible creatinine elevation in 4 pts: 3 pt with gr 1; 1 pt with gr 2 secondary to DLT. Partial response was in 1 pt (NET); stable disease in 7 pts, including NET (2), NSCLC (2), CRC (1), sarcoma (1), and unknown primary (1). Therapy duration 14+-88+ weeks. Soluble GRP78 is detected in the plasma of patients at baseline. Conclusions: NKP-1339is well tolerated with manageable side effects. Single agent activity is noted in multiple tumors including NET. Results from the expanded cohort and pre/post-therapy PD will be presented. Phase II single agent NKP-1339 and phase I NKP-1339 combination trials are planned.

scholarly journals Agnostic evaluation of ipilimumab and nivolumab association: a metanalysis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Paolo Marchetti ◽  
Andrea Botticelli ◽  
Antonio Paolo Ascierto ◽  
Giuseppe Curigliano ◽  
Diana Giannarelli
Keyword(s):  
Meta Analysis ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Added Value ◽  
Combination Strategy ◽  
Free Survival ◽  
Multiple Tumor ◽  
Single Agent Therapy ◽  
Tumor Types

Abstract Background Ipilimumab and Nivolumab, targeting the molecules CTLA-4, PD-1, respectively,have shown efficacy against several types of cancer. Despite these results, only a small percentage of patients maintains a long-lasting effect. Even Ipilimumab, in combination with nivolumab, has demonstrated a significant clinical benefit in multiple tumor types. However, no trial has been designed with the primary endpoint to compare the efficacy of nivolumab plus ipilimumab combined, compared to nivolumab alone. Hence, the added value of ipilimumab in the combination has not clearly been established yet. The aim of this study was to demonstrate the superiority of the combination strategy compared to the single agent therapy. Materials and methods We performed a meta-analysis of Phase I-II-III Clinical Trials, published from 2010 up to 2020, in which the combination of ipilimumab plus nivolumab was compared to nivolumab alone. We extracted ORR, OS and PFS HR on the basis of treatment from the subgroup analysis of each trial. Results A total of 7 trials were included in the present meta-analysis. Overall, 1313 patients were treated with the nivolumab plus ipilimumab combination compared to 1110 patients treated with nivolumabalone. All trials reported the Objective response rate(ORR), no heterogeneity was found among studies and the pooled Odds Ratio was highly in favor of the nivolumab plus ipilimumab combination with respect to nivolumab alone (1.683; 95% CI: 1.407–2.012; P < 0.0001). Three studies were considered for Progression free survival (PFS) analysis, and the pooled Hazard Ratio favored the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.807; 95% CI: 0.719–0.907; P < 0.0001). The Overall survival(OS) endpoint was considered only in 2 trials, and the pooled HR favored, also in this case, the combination of nivolumab plus ipilimumab with respect to nivolumab alone (0.87; 95% CI: 0.763–0.997; P = 0.045). Conclusions The combination of ipilimumab plus nivolumab seems to be superior to nivolumab alone in cancer patients, regardless of histology.

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