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Investigational immunotherapy

Investigational immunotherapy

Investigational immunotherapy

966P - Diabetes therapy burden as proxy of impairment of immune checkpoint inhibitors efficacy

Presentation Number
966P
Speakers
  • Alessio Cortellini (London, United Kingdom)

Abstract

Background

Chronic hyperglycemia is known to induce immune dysfunctions and multiple studies has identified resistance/adherence to insulin therapy as barriers to achieving an optimal glycaemic control in patients with diabetes mellitus (DM) after front line metformin failure. How DM affects the efficacy of immune checkpoint inhibitors (ICI) is yet to be defined.

Methods

We evaluated the impact of DM in a retrospective cohort of patients with advanced cancer treated with ICI at 22 Institutions. The diabetes medication burden (DMB) at ICI initiation was used as a proxy of long-term/poorly controlled DM. Patients with a high DMB were on high dose metformin (> 1000 mg) either alone or in combination with insulin therapy and/or other oral antidiabetics. Patients with low DMB were on oral antidiabetics/insulin with or without low dose metformin. In a subgroup of 133 patients the inter-relationships between the median baseline glycemia (MBG) (computed upon up to 3 fasting blood glucose tests within 3 months of ICI initiation) and the neutrophil-to-lymphocyte ratio (NLR) were assessed.

Results

From June 2014 to November 2020, 1395 patients treated with CTLA-4 (2.5%) and PD-1/PD-L1 (97.5%) inhibitors were included. Median age was 68 years; male/female ratio 888/507. Primary tumours were: NSCLC (54.7%), melanoma (24.7%), renal cell carcinoma (15.0%) and others (5.6%). 148 (10.6%) and 78 (5.6%) were on low and high DMB, respectively. The DMB was proportionally associated to both an increasing MBG (5.6, 7.5 and 9.5 mmol/L) and median NLR (3.8, 4.1 and 5.6). After adjusting for gender, age, BMI, primary tumour, treatment line, burden of disease, performance status and corticosteroids, patients on high DMB were confirmed to have shorter progression free survival (PFS) (HR 1.39[95%CI: 1.09-1.78] p=0.0075) and overall survival (OS) (HR 1.44 [95%CI:1.09-1.90] p = 0.0087) as compared to non-DM. MBG significantly predicted for the NLR [F(1,131) = 4.09, p = 0.04), R2 of .030], and was associated to a high NLR (≥ 4) even after adjusting for corticosteroids (OR = 1.68[95%CI: 1.23 – 2.29], p = 0.0011).

Conclusions

Long-term/poorly controlled diabetes may impair ICI efficacy. Strategies to improve glycaemic control should be pursued in patients about to start an immunotherapy.

Legal entity responsible for the study

University of L'Aquila.

Funding

Has not received any funding.

Disclosure

A. Cortellini: Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Expert Testimony: SunPharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. D.J. Pinato: Financial Interests, Personal, Speaker’s Bureau: ViiV Healthcare; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Advisory Board: EISAI; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.

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Investigational immunotherapy

967P - The time of anti-PD-1 infusion improves survival outcomes by fasting conditions simulation in non-small cell lung cancer

Presentation Number
967P
Speakers
  • Anna Vilalta (Pamplona, Spain)

Abstract

Background

Although PD-1 blockade represents a major breakthrough in non-small cell lung cancer (NSCLC) treatment, primary/acquired resistance frequently occurs. Fasting-mimicking conditions increase tumor immunogenicity and sensitize lung tumors to PD-1 blockade by reducing insulin-like growth factor 1 (IGF-1). We studied whether the time of anti-PD-1 infusion, which might reflect fasting conditions, may correlate with clinical outcomes in NSCLC patients.

Methods

NSCLC patients from two Spanish academic institutions treated with anti-PD-1 were categorized in two groups according to the time of anti-PD-1 infusion (A: patients who received at least one of the first four treatment cycles before 12 pm; B: patients receiving all first four cycles after 12 pm). On treatment iRECIST assessment was performed every 8-12 weeks. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints were disease control rate (DCR) at the first radiologic evaluation and correlation between circulating levels of IGF-1 and related proteins and clinical outcomes.

Results

Of the 197 patients enrolled (72.1% males; median follow up of 9.6 months), 104 (52.8%) were assigned to group A and 93 to group B (47.2%). Most patients presented non-squamous cell carcinoma (72.6%) and received anti-PD-1 monotherapy (N=166 patients; 84.3%). The remaining patients (N=31) received anti-PD-1 plus chemotherapy combinations. In the univariate analysis, median PFS was 6.5 months in group A and 3.2 months in group B (p=0.066). Median OS was 16.1 and 7.4 months, respectively (p=0.003). In a multivariate model adjusted by age, gender, histology, treating institution and treatment line, HR for PFS was 0.418 (95% CI 0.275-0.634; p<0.001) and HR for OS was 0.545 (95% CI = 0.352–0.845; p=0.007). No significant differences in DCR at first evaluation were observed between groups. Circulating levels of IGF-1-related factors involved are being currently analyzed and will be presented at the meeting.

Conclusions

Anti-PD-1 administration before 12 pm significantly improved PFS and OS in NSCLC patients suggesting a potential correlation with fasting. Circulating levels of metabolic factors involved might explain these results.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

968P - Association between use of antibiotics (ATB) and clinical outcomes with tislelizumab (tisle) monotherapy

Presentation Number
968P
Speakers
  • Zheng-Gang Ren (Shanghai, China)

Abstract

Background

Immune checkpoint inhibitors (ICIs) have changed the therapeutic landscape of many cancers but ICI efficacy varies greatly. Retrospective analyses showed ATB may have a negative impact on ICI efficacy. However, heterogeneous results induced by ATB observed across studies may be due to population diversity, different definitions of ATB use, limited sample size, etc.

Methods

Data from 5 tisle monotherapy studies were analysed. Patients were dichotomized by timing of IV/oral ATB use; ±30 days of Day 1 tisle treatment was ‘ATB+’, otherwise ‘ATB-’. Propensity score weighting was employed to correct for bias from unbalanced baseline characteristics. Survival probability was estimated by the Kaplan–Meier method and compared by log-rank test. Cox model of overall survival (OS) was used to compute hazard ratio (HR) and 95% confidence interval (CI). Landmark analysis was conducted to explore the association of ATB use and OS across time to mitigate guarantee-time bias.

Results

217/1183 (18%) patients received ATB. OS was significantly decreased in the ATB+ group vs the ATB- group (HR: 1.5; 95% CI: 1.3–1.9, p<0.0001). In the ATB+ group, OS was significantly decreased with prophylactic vs non-prophylactic ATB treatment (HR: 2.5; 95% CI: 1.5–4, p<0.0001). A significant association between ATB use and decreased OS was shown in patients with esophageal squamous cell carcinoma (ESCC) (HR: 3.0; 95% CI: 1.3–7.2, p<0.01), hepatocellular carcinoma (HCC) (HR: 1.8; 95% CI: 1.1–2.9, p<0.01) and urothelial carcinoma (UC) (HR: 2.3; 95% CI: 1.3–3.9, p<0.001). A worse trend in OS was observed for non-small cell lung cancer (NSCLC) (HR: 1.6; 95% CI: 0.74–3.6, p=0.26). Landmark analysis identified the time intervals, as related to Day 1 of tisle treatment, when ATB use had a significant negative impact on OS per tumor type: Day -15–45 for ESCC, Day 19–45 for HCC, and Day -5–133 for UC. No significant time interval emerged in NSCLC.

Conclusions

In this pooled analysis, a negative association was observed between ATB use during tisle treatment and OS in a pooled population and in ESCC, HCC and UC. Time intervals in which ATB use had a significant negative impact on OS were identified per indication. Prophylactic ATB use showed a poorer OS outcome vs non-prophylactic ATB use.

Clinical trial identification

Pooled analysis of the following trials: BGB-A317-001; NCT02407990 BGB-A317-102; CTR20160872 BGB-A317-203; NCT03209973 BGB-A317-204; CTR20170071 BGB-A317-208; NCT03419897.

Editorial acknowledgement

Third-party medical writing assistance, under the direction of the authors, was provided by Jenny Feehan, BSc, of Ashfield MedComms, and was funded by BeiGene, Ltd.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

Z. Ren: Financial Interests, Other, Honoraria: BeiGene, AstraZeneca, F. Hffmann-La Roche, and Merck Sharp & Dohme; Financial Interests, Advisory Role: AstraZeneca, F. Hoffmann-La Roche Ltd, Merck. Y. Gao: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd.; Financial Interests, Other, Travel, Accommodations, Expenses: BeiGene, Ltd. C. Wei: Financial Interests, Full or part-time Employment: BeiGene, Ltd. X. Li: Financial Interests, Full or part-time Employment: BeiGene, Ltd. S. Liu: Financial Interests, Full or part-time Employment: BeiGene, Ltd. J. Zhang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. L. Wang: Financial Interests, Full or part-time Employment: BeiGene, Ltd. Y. Wu: Non-Financial Interests, Sponsor/Funding: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Pfizer and Roche; Non-Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Merck, MSD, Roche and Takeda; Financial Interests, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Roche and Sanofi.

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Investigational immunotherapy

969P - Effect of angiotensin II inhibition on non-small cell lung cancer response to immune checkpoint blockers

Presentation Number
969P
Speakers
  • Patricia M. Pereira (Lisbon, Portugal)

Abstract

Background

The renin-angiotensin system (RAS) is an important signaling system within the tumor microenvironment, promoting both malignant and stromal cell proliferation. Angiotensin II (AngII) is the main effector hormone, acting predominantly by the signaling of angiotensin II type 1 receptor (AT1R). Preclinical data show that AngII increases TGF-β production through AT1R signaling and decreases TGF-β through AT2R signaling. Thus, the overlap of these pathways may have a critical role in carcinogenesis, as well as immune evasion and inhibiting AT1R may enhance clinical responses in combination with immune checkpoint inhibitors (ICI). Here we report efficacy of ICI in patients (pts) with non-small cell lung cancer (NSCLC) concomitantly taking RAS inhibitors (RASi).

Methods

We conducted a single-center, retrospective analysis of NSCLC pts treated with ICI from September 2015 to August 2019. Clinical data was collected and groups were defined as pts treated with Ang receptor blockers (ARBs), Ang converting enzyme inhibitors (ACEi) or none (control) at the time of ICI initiation. Statistical analyses were performed using Cox regression method.

Results

In total, 127 pts with NSCLC were included, where 15 (11.8%) were concomitantly taking ARBs and 20 (15.7%) ACEi. Baseline characteristics were similar in all groups. The ARB group had a prolonged median PFS and OS compared to the control group (HR 0.401, 95%CI 0.174-0.929 and HR 0.438, 95%CI 0.189-1.015, respectively). Interestingly, no statistically impact in PFS (HR 0.872, 95%CI 0.460-1.654) or OS (HR 0.747, 95%CI 0.393-1.419) was observed in ACEi group compared with control group. ARB use was also associated with an increase in ORR (26.7%), in contrast ACEi use was not associated with ORR improvement (12.5%) when compared with pts not taking RASi (14.9%).

Conclusions

Concomitant ARB use was associated with an improvement in PFS, OS and near doubling in ORR with ICI. This same benefit was not seen with ACEi. This discrepancy may be due to selective blockade of AT1R by ARBs. Thus, ARBs prescription concomitant to ICI seems to be associated with better outcomes and tumor response in pts with NSCLC. These results should be validated in prospective trials.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

970P - Assessment of anti-PD-1 antibody and immune complex binding to Fcγ receptors and clinical implications

Presentation Number
970P
Speakers
  • Elena Daveri (Milan, Italy)

Abstract

Background

Anti-tumor immunity of therapeutic anti-PD-1 monoclonal antibodies (mAbs), such as nivolumab and pembrolizumab, rely on their ability to antagonize the PD-1/PD-L1 interaction, rescuing exhausted T-cell immunity. However, upon forming a stable sPD-1-antiPD-1mAb immune complex (PD-1 IC), anti-PD-1 mAbs can trigger immunosuppressive activity in fragment crystallizable receptor (FcR)-expressing myeloid cells.

Methods

The binding of anti-PD1 and PD-1-IC is evaluated in vitro by surface plasmon resonance (SRP) (BiacoreTM T200, Cytiva), through the interaction of FcγRI/CD64, FcγRIIa/CD32a, FcγRIIb/CD32b, FcγRIIIa/CD16a and FcγRIIIb/CD16b and anti-PD1 mAbs or IC-PD-1 on a CM5 sensor chip. The presence and quantification of sPD-1 and PD-1 ICs in plasma of anti-PD-1 mAb-treated patients is assessed by customized ELISAs and western-blot approaches.

Results

Sensorgrams analyses revealed that anti-PD1 and PD-1-IC display detectable levels of binding all the FcγRs tested, albeit with diverse degrees. For FcγRIIIa/CD16a and FcγRIIIb/CD16b, dissociation phase was clearly slowest for PD-1 IC with respect to the monomeric mAb. Instead, the interaction with FcγRI/CD64, FcγRIIa/CD32a, FcγRIIb/CD32b have any major difference in the overall affinity of anti-PD-1 mAbs versus PD-1 IC, but at least CD32a/b show a slightly different kinetic of binding that may reflect a different signal for the cells involved. Data concerning the quantitative/semiquantitative evaluation of PD-1 IC concentration in plasma of cancer patients treated with nivolumab or pembrolizumab, will be presented.

Conclusions

Despite the IgG4 subclass is expected to display the lowest binding affinity to Fcγs, we report here that anti-PD-1 therapeutic antibodies bind significantly to FcγRs particularly if stabilized in the IC form by engaging soluble PD-1. This evidence could introduce novel functional properties to these therapeutic agents, with potential detrimental effects on their clinical efficacy. Our findings imply that tools to antagonize PD-1-related exhaustion by Fc-null mAbs or non-mAb-based strategies could be preferred to engage full-fledged antitumor immune responses without unwanted effects related to FcR triggering.

Legal entity responsible for the study

L. Rivoltini, Immunotherapy of Human Tumor, Fondazione IRCCS Istituto Nazionale dei Tumori Milano.

Funding

5x1000 Funds 2014, Italian Ministry of Health (MoH) Institutional grant from Fondazione IRCCS, Istituto Nazionale dei Tumori [grant number BRI2017]; PRECIOUS Project-Horizon 2020 [grant number 686089].

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

971P - Is there a clinical benefit of nivolumab + ipilimumab in patients older than 75 years with advanced solid tumors?

Presentation Number
971P
Speakers
  • Thierry Landre (Sevran, France)

Abstract

Background

Combination therapy with nivolumab + ipilimumab (Nivo+Ipi) has been widely used for clinical treatment in recent years, which has a better survival benefit. However, not all patients can derive clinical benefit from this combination immunotherapy.

Methods

We performed an age subgroup analysis of published randomized control trials concerning "Nivo+Ipi" versus standard therapy in patients with advanced solid tumours. Overall Survival (OS) among the elderly (≥ 75 years) was compared with that of younger patients (≥ 65 to < 75 years). Hazard ratios (HRs) with their 95% confidence interval (CI) were collected from the studies and pooled. A fixed-effect model was used.

Results

Few studies have been published corresponding to our inclusion criteria. Two studies (CheckMate 9LA and CheckMate 227) assessed "Nivo+Ipi" in Non-Small Cell Lung Cancer (NSCLC), one study (CheckMate 214) assessed "Nivo+Ipi" in Renal-Cell Carcinoma (RCC); the last one (CheckMate 743) assessed "Nivo+Ipi" in Malignant Pleural Mesothelioma. Our pooled-analysis included 373 patients older than 75 years (308 with thoracic cancers and 65 with RCC) and 1140 patients between 65 and 75 years (882 thoracic cancers and 258 RCC). All patients were mostly men (68%), with good Performance Status (0 or 1). For patients ≥75 years, OS of the "Nivo+Ipi" arm was similar to that of the control arm (HR = 0.98; 95% CI 0.76-1.26; p = 0.86). Conversely, among younger patients (≥65 to < 75 years), a statistically significant OS benefit was observed with "Nivo+Ipi" (HR = 0.74; 95 % CI 0.64-0.85; p < 0.0001). However, the difference observed between subgroups was not statistically significant (p= 0.06).

Conclusions

Due to the low number of elderly patients in clinical trials, there is an uncertainty to prescribe the combination "Nivo+Ipi" for older population (≥75 years). Further studies are warranted.

Legal entity responsible for the study

T. Landre.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

973P - A phase II study of PDR001 among patients with recurrent and/or metastatic esophageal squamous cell carcinoma: An interim analysis of KM-12

Presentation Number
973P
Speakers
  • Dong Ki Lee (Seoul, Korea, Republic of)

Abstract

Background

Programmed cell death protein 1 (PD-1) inhibitors emerged as a promising treatment option for esophageal cancer refractory to standard treatment. PDR001 (spartalizumab) is a humanized IgG4 monoclonal antibody targeting PD-1. We report the results of a single-arm phase II study of PDR001 in the treatment of esophageal squamous cell carcinoma (ESCC) in Korea.

Methods

Inclusion criteria were histologically proven ESCC with a measurable lesion refractory or intolerant to standard therapy. We collected the information regarding patients’ baseline characteristics and responses measured by Response Evaluation Criteria in Solid Tumours version 1.1. The primary endpoint was the overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival, overall survival, and duration of response.

Results

Forty-nine patients were screened and a total of 44 eligible patients with ESCC were enrolled. At the data cut-off, the response of 3 patients was pending. The ORR was 18.2% (95% confidence interval [CI], 9.3% to 32.2%), and DCR was 56.8% (95% CI, 42.2% to 70.3%). The most frequent treatment-related adverse events (TRAEs) were grade 1 or 2 hypothyroidism (n = 4) and rash (n = 4). Grade 3 TRAEs included amylase elevation (n = 1), dry mouth (n = 1), sore throat (n = 1), and myalgia (n = 1) but none of them led to treatment delay or discontinuation. No grade 4 or greater TRAEs were reported.

Conclusions

The study is ongoing and PDR001 showed modest clinical benefits with manageable toxicity in refractory ESCC. The efficacy and safety in this population were consistent with those of previous PD-1 inhibitor trials. Biomarker analysis including programmed death ligand 1 (PD-L1) expression are planned.

Clinical trial identification

NCT03785496.

Editorial acknowledgement

The study was supported by K-MASTER project. Novartis provided PDR001.

Legal entity responsible for the study

The authors.

Funding

Novartis.

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

974P - Genetic and molecular analysis of solid tumors with hyperprogressive disease after treatment with immunotherapy

Presentation Number
974P
Speakers
  • Daniel Trotier (Cincinnati, United States of America)

Abstract

Background

Immunotherapy (IO) has emerged as a powerful treatment option in many advanced cancers. An alarming response phenotype termed hyperprogressive disease (HPD) has been described, in which tumors exhibit rapid growth upon initiation of IO. HPD has been linked to adverse clinical outcomes, however, the mechanisms that underlie HPD remain poorly understood.

Methods

Patients treated between 1/2013 and 5/2019 at the University of Cincinnati that had complete Caris Life Sciences molecular profiling were included. Baseline clinical characteristics and treatment history were extracted from the medical record. All solid tumor types were included. Patients with incomplete treatment or imaging data, or no RECIST measurable disease were excluded. Target lesions were recorded according to RECIST 1.1. HPD was defined as doubling of the tumor growth rate (TGR) after initiation of IO. Time-to-treatment-failure (TTF) was defined as time from IO initiation to clinical or radiologic progression, death, toxicity or new treatment start. Clinical characteristics and genomic profiles of HPD and non-HPD groups were compared using student’s t-test, chi-squared test, and Fisher’s exact test. 136 patients were evaluated. 34 patients had the requisite scans and measurable disease to qualify for TGR calculation.

Results

We identified 7/32 (22%) patients who met criteria for HPD. HPD was associated with older age at diagnosis (63.5 vs 59.3), decreased overall survival (3.8 vs 5.5 months), and shorter TTF (7.8 vs 10.1 months), although not statistically significant. Molecular profiles of HPD and non-HPD patients showed similar frequency of mutations in TMB, TP53, EGFR, RTK co-factors and DDR pathways. TTF<3 months was correlated with more frequent EGFR, and NOTCH mutations. TTF>3 months was associated with mutations in DDR and WNT pathways.

Conclusions

There were no statistically significant clinical or genomic differences between HPD and non-HPD patients. TTF analysis identified EGFR, NOTCH, DDR and WNT pathways as possible predictors of response to IO. This study is limited by small sample size, but may support the hypothesis that HPD represents the natural disease course of some patients with aggressive cancers.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J.E. McGrath: Financial Interests, Institutional, Full or part-time Employment: Caris Life Sciences. T. Wise-Draper: Financial Interests, Personal, Advisory Board: Exicure; Financial Interests, Personal, Invited Speaker: Physician Education Resource; Financial Interests, Personal, Advisory Board: Rakuten Medical; Other, Personal, Other, Consultant: Shattuck Labs; Financial Interests, Personal, Ownership Interest: High Enroll; Financial Interests, Personal and Institutional, Principal Investigator: Alkermes; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal and Institutional, Principal Investigator: BMS; Financial Interests, Personal and Institutional, Principal Investigator: Boston Medical; Financial Interests, Personal and Institutional, Principal Investigator: Debio Pharm; Financial Interests, Personal and Institutional, Principal Investigator: Eli Lilly; Financial Interests, Personal and Institutional, Principal Investigator: EMD Serono; Financial Interests, Personal and Institutional, Principal Investigator: Epizyme; Financial Interests, Personal and Institutional, Principal Investigator: Exicure; Financial Interests, Personal and Institutional, Principal Investigator: Iovance; Financial Interests, Personal, Research Grant: Merck & Co.; Financial Interests, Personal and Institutional, Principal Investigator: Replimune; Financial Interests, Personal and Institutional, Principal Investigator: Shattuck Labs; Financial Interests, Personal, Research Grant: Tesaro/GSK. All other authors have declared no conflicts of interest.

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Investigational immunotherapy

975P - Impact of body mass index on the efficacy of immune checkpoint inhibitors in cancer

Presentation Number
975P
Speakers
  • Alejandro Rios Hoyo (Barcelona, Spain)

Abstract

Background

Anti-PD-1/PD-L1 agents have revolutionized the treatment of advanced cancer. However, many patients still do not benefit from these treatments. We sought to evaluate the impact of body mass index on the efficacy of anti-PD-1/PD-L1 drugs.

Methods

Retrospective data was collected from patients with advanced NSCLC (non-small cell lung cancer), genitourinary cancers, or malignant melanoma who received immune checkpoint inhibitor (ICI) treatment with anti-PD-1 or anti-PD-L1. Parameters evaluated included stage, ECOG Performance Status (PS) at initiation of ICI, development of immune related adverse events (irAE), and body mass index (BMI). Univariate and multivariate analyses were performed to assess the association between these parameters and overall survival (OS). The latter was calculated since the first administration of ICI.

Results

One hundred fourteen patients were included in this study. The most frequent tumor origin was lung (70.2%), followed by genitourinary (22.8%) and melanoma (7%). 84.4% of the patients received treatment with an anti-PD-1 agent, whereas 15.5% received treatment with an anti-PD-L1 agent. Patients with a BMI greater than 25 kg/m2 represented 49.2% of the cases. According to BMI classification, patients with underweight, normal-weight, and equal to or greater than overweight, had a median OS of 3.73 months (m), 15.76m, and 19.60m respectively (global p value of <0.001). Statistical analysis revealed that for every unit of increase in BMI, risk of death was reduced by 6%. PS, stage, and BMI remained independently associated with outcome in the multivariate analysis (Table).

Multivariate analysis for overall survival

Variables HR (95% CI) p-value
ECOG PS 2 6.63 (2.56 – 17.21) <0.001
Advanced stage at baseline 1.85 (1 - 3.41) <0.049
Overweight and obesity (BMI >25) 0.21 (0.07 – 0.59) 0.003

Conclusions

Our results suggest that low BMI is associated with worse outcome in patients with advanced cancer treated with ICIs. Upfront nutritional assessment and measures might improve the results of treatments with ICI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Arriola: Other, Institutional, Invited Speaker: BMS; Other, Institutional, Invited Speaker: AstraZeneca; Other, Institutional, Invited Speaker: Roche; Other, Institutional, Invited Speaker: MSD; Other, Institutional, Invited Speaker: Pfizer; Other, Institutional, Invited Speaker: Lilly; Other, Institutional, Invited Speaker: Boehriger Ingelheim. All other authors have declared no conflicts of interest.

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Investigational immunotherapy

976P - The 30-day mortality rate after first cycle of immunotherapy

Presentation Number
976P
Speakers
  • Osman Sutcuoglu (Ankara, Turkey)

Abstract

Background

The aim of this study is to determine the causes of death in patients who received at least one dose of immunotherapy and died within 30 days after the first dose of immunotherapy regardless of the purpose of treatment and cancer type. The second aim of the study is to evaluate the characteristics of the disease and patients before starting immunotherapy and to determine the prophylactic features to be taken to reduce the complications of immunotherapy.

Methods

The data of a total of 1432 patients treated with immunotherapy in six tertiary referral hospital were retrospectively analyzed.

Results

It was determined that 34 (2%) of the patients died within 30 days following the first dose of immunotherapy. Approximately half of the patients (55%) had good performance at the beginning of immunotherapy (ECOG 0-1), again half of the patients had no comorbidity. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second or subsequent line of therapy. The most common diagnosis of death patients were malignant melanoma (40%), lung cancer (24%) and renal cell carcinoma (20%) and other (16%). Twenty-three patients died in the hospital, the most common cause of death was disease progression and thromboembolic events (Table).

Information on death occurred in the first 30 days after immunotherapy

All patients
N=34 (%)
Median time from immunotherapy to death (min-max) (days) 26 (2-30)
Immunotherapy-related immune side effect
Autoimmune nephritis 2 (6%)
Autoimmune hepatitis 1 (3%)
Myocarditis 1 (3%)
Adrenal insufficiency 1 (3%)
Myastenia gravis 1 (3%)
None 28 (82%)
Hyperprogression
Yes 3 (10%)
No 31 (90%)
Death place
Hospital 23 (66%)
Home 9 (28%)
Nursing home 2 (6%)
Cause of death
Disease progression 7 (40%)
Sepsis 5 (15%)
Pulmonary embolism 4 (12%)
Immune side effect 3 (9%)
Myocardial infarction 3 (9%)
Gastrointestinal system bleeding 1 (3%)
Unknown 11 (32%)

Conclusions

The relationship between first 30-day mortality and disease progression/thromboembolic events has been demonstrated in patients using immunotherapy in the treatment of metastatic cancer.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Investigational immunotherapy

977P - Interim results of phase I dose escalation study of YBL-006: A novel anti-PD-1 monoclonal antibody in advanced solid tumors

Presentation Number
977P
Speakers
  • Keun-Wook Lee (Seongnam, Korea, Republic of)

Abstract

Background

YBL-006 is a fully human anti-programmed death-1 (PD-1) antibody with a wider binding interface of the PD-1/YBL-006 complex and higher affinity compared to that of other PD-1 antibodies, which showed a favorable safety profile and a potent anti-tumor efficacy in animal models.

Methods

A modified “3+3” design, with the first patient dosed at 0.5 mg/kg (mpk), was followed by conventional dose escalation of 2, 5, and 10 mpk IV. Dose escalation cohort explored the safety, pharmacokinetics (PK), PD-1 receptor occupancy (RO), serum IFN-γ level and tumor response. Adverse events (AEs) were graded using the CTCAE v5. Tumor response was assessed using the RECIST v1.1 every 8 weeks. Exploratory biomarker analysis included whole exome sequencing to assess tumor mutational burden (TMB) and Lunit SCOPE IO to assess the density of intra-tumoral tumor-infiltrating lymphocyte (TIL). The cut-off date for analysis was Apr 27th, 2021.

Results

Total of 11 patients with advanced solid tumors were enrolled in the escalation cohort. YBL-006 showed a linear PK prolife in terms of Cmax and area under the curve by dose escalation and approximately 8 days of T1/2. Both PD-1 RO and serum IFN-γ increased by > 2 times 8 h after the first dose. No dose limiting toxicity (DLTs) or deaths related to YBL-006 have been reported. The most common AEs of Grade 2 ≥ related to YBL-006 were rash (21.7%), fatigue (13%), fever (13%) and hypothyroidism (4.3%). Ten patients were available for tumor response evaluation and their best overall responses included 1 complete response (penile squamous cell carcinoma, 2 mpk), 1 partial response (anal squamous cell carcinoma, 2 mpk) with durable responses lasting more than 30+ and 14+ weeks respectively, and 4 stable disease. Tumor samples of both of 2 responders harbored high levels of TMB (8.3 and 9.3 per megabase) and intra-tumoral TIL density (66.1% and 95.8%).

Conclusions

YBL-006 is well tolerated, and AEs are manageable with the results of no DLTs occurred and the maximum tolerated dose was not reached until progressing to the 10 mpk. Dose expansion cohort using flat dosing is planned.

Clinical trial identification

NCT04450901.

Legal entity responsible for the study

Y-Biologics Inc.

Funding

Y-Biologics Inc.

Disclosure

M. Kim: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics. J. Yoon: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics; Non-Financial Interests, Project Lead: Y-Biologics. H. Lee: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics; Financial Interests, Personal, Leadership Role: Y-Biologics. All other authors have declared no conflicts of interest.

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