EFFICACY AND SAFETY OF IMMUNE CHECKPOINT INHIBITORS (ICIS) FOR TREATMENT OF ADVANCED SOLID TUMORS IN OCTOGENARIAN PATIENTS

2019 ◽  
Vol 10 (6) ◽  
pp. S113 ◽  
Author(s):  
S. Mebarki ◽  
M. Gisselbrecht ◽  
E. Fabre ◽  
E. Mercadier ◽  
S. Oudard ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Solid Tumors ◽  
Efficacy And Safety

Preliminary safety, efficacy, and pharmacokinetics (PK) results of KN046 (bispecific anti-PD-L1/CTLA4) from a first-in-human study in subjects with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2554-2554 ◽  
Author(s):  
Jermaine Coward ◽  
Vinod Ganju ◽  
Ramin Behzadigohar ◽  
Kenneth Kwong ◽  
June Xu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Human Study ◽  
Safety Data ◽  
Advanced Solid Tumors ◽  
Duration Of Treatment ◽  
Efficacy Evaluation

2554 Background: KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD1 and CTLA-4 interaction with CD80/CD86. KN046 has a wild type IgG1 Fc portion that preserves intact effector functions, such as depletion of Tregs in tumor microenvironments. This first-in-human study evaluated the safety, tolerability, PK and preliminary efficacy of KN046 in subjects with advanced solid tumors. Methods: This traditional “3+3” dose-escalation design study enrolled patients (pts) with advanced unresectable or metastatic solid tumors refractory or intolerant to standard therapies. Previous treatment from PD1 or PD-L1 immune checkpoint inhibitors was allowed. KN046 was administered intravenously Q2W. Dose limit toxicity (DLT) evaluation period is 28 days. The planned dose levels (DL) were 0.3, 1, 3, 5 and 10 mg/kg. Efficacy evaluation was performed by RECIST 1.1 every 8 weeks. Results: As of Dec 13, 2018, 10 pts had been enrolled (0.3 mg/kg, n = 1; 1 mg/kg, n = 3; 3 mg/kg, n = 3; and 5 mg/kg, n = 3). Median duration of treatment was 8 (range: 2-24) weeks. 1 DLT was observed at 5 mg/kg dose (a grade 3 immune-related hepatitis without elevation in total bilirubin; reversible in two weeks). The most common (≥30%) treatment-emergent AEs (TEAE) were Fatigue, Diarrhea, Nausea, Vomiting. Six immune-related TEAEs (Abdominal pain lower, Arthralgia, Hepatic function abnormal, Hyperthyroidism, Nausea and Transaminitis) were observed in 3 pts. One pt with NSCLC from 3 mg/kg cohort had confirmed completed response. Two pts (TNBC and nivolumab refractory RCC) from 1 mg/kg cohort had shown long-term stable disease ( > 12 weeks). Faster clearance of KN046 was observed at lower dose might be due to target-mediated clearance. T1/2 is approximately 7~9 days at doses of 3 mg/kg and above when saturation occurs. Conclusions: Single agent KN046 has an acceptable safety profile and is in line with previously reported safety data from other immune checkpoint inhibitors. Preliminary efficacy results are promising. PK data from initial 4 cohorts support Q2W schedule. The study is currently ongoing at dose level of 5 mg/kg Q2W. Clinical trial information: NCT03529526.

Effect of concurrent beta-blocker use in patients receiving immune checkpoint inhibitors for advanced solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15068-e15068
Author(s):  
Vaibhav G. Patel ◽  
Qian Qin ◽  
Bo Wang ◽  
Mahalya Gogerly-Moragoda ◽  
George Mellgard ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Model Systems ◽  
Beta Blockade ◽  
Clinical Activity ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Adrenergic Signaling

e15068 Background: Stress-induced adrenergic signaling suppresses the immune system. In animal model systems, pharmacological beta-blockade stimulated CD8+ T-cell activity, and further, it improved clinical activity of immune checkpoint inhibitors (ICI) in inhibiting tumor growth. Herein, we investigate the effect of beta blockers (BB) on clinical outcomes of patients receiving ICI in advanced solid tumors. Methods: We retrospectively evaluated patients with solid tumors treated with at least 2 doses of ICI at our institution from December 2010 to April 2017. The primary outcome was disease control rate (DCR), as defined by radiographic complete response, partial response, or stable disease, by RECIST 1.1 criteria. The primary predictor was use of BB (β1-selective BB vs. no BB; non-selective BB vs no BB). The primary predictive variable was analyzed using multivariate logistic regression model controlling for several parameters including patient demographics, co-morbidities, ECOG performance status, and tumor type and location of metastases. All tests were two-sided at the significant level of 0.05. Results: We identified 298 evaluable patients with median age of 66.5 (31-95). Of these patients, 200 (67%) did not use BB, 75 (25%) used β1-selective BB, and 23 (8%) used non-selective BB. In multivariate analysis, use of β1-selective BB was significantly associated with improved DCR compared to no BB (ORR 2.43, 95% CI 1.31-4.51, P = 0.005), while use of non-selective BB was not associated with improved DCR (ORR 1.71, 95% CI 0.65-1.47, P = 0.27). Conclusions: The concurrent use of BB may enhance the clinical activity of ICI, particularly β1-selective BB. Our findings warrant further investigation to understand the interaction of β1- and β2-adrenergic signaling and antitumor immune activity, and potentially explore a combination strategy of ICI and BB.

A CT-based Radiomics Signature Is Associated with Response to Immune Checkpoint Inhibitors in Advanced Solid Tumors

Radiology ◽  
2021 ◽  
pp. 200928
Author(s):  
Marta Ligero ◽  
Alonso Garcia-Ruiz ◽  
Cristina Viaplana ◽  
Guillermo Villacampa ◽  
Maria V. Raciti ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Solid Tumors ◽  
Radiomics Signature

scholarly journals Retreatment with immune checkpoint inhibitors in solid tumors: a systematic review

2020 ◽  
Vol 12 ◽  
pp. 175883592097535
Author(s):  
Kaili Yang ◽  
Jiarui Li ◽  
Zhao Sun ◽  
Lin Zhao ◽  
Chunmei Bai
Keyword(s):  
Systematic Review ◽  
Disease Progression ◽  
Solid Tumors ◽  
Prospective Studies ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cochrane Library ◽  
Efficacy And Safety ◽  
Grade 3

Background: A large proportion of patients eventually experience disease progression despite treatment with immune checkpoint inhibitors (ICIs), but subsequent treatment options are limited for this population. Retreatment with the same or different types of ICIs is a possible strategy, but the clinical efficacy and safety data are limited. This systematic review aims to evaluate the efficacy and safety of ICIs retreatment in patients with solid tumors after disease progression to previous ICIs. Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and major meeting libraries for prospective studies. The primary outcomes included the objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), and the incidence of grade ⩾3 immune-related adverse events (irAEs). Results: We identified 22 prospective studies including 1865 patients. For disease progression after CTLA-4 inhibitors, three studies evaluated anti-CTLA-4 retreatment. The ORR was 12–23%, the DCR was 48.4–67.7%, and the mOS was 12 months. The incidence of grade ⩾3 irAEs was 5.9–25%. Four studies evaluated anti-programmed cell death protein 1 (PD-1) retreatment. The ORR was 22–36%, the DCR was 40–64%, and the mOS was 13.4–20.6 months. The incidence of grade ⩾3 irAEs was <10%. For disease progression after PD-(L)1 inhibitors, 13 studies evaluated anti-PD-(L)1 retreatment. The ORR was 5–53%, the DCR was 38–83%, and the mOS was 13.9 months. The incidence of grade ⩾3 irAEs was 0–15% for patients retreated with single anti-PD-(L)1 agent, but was higher (0–64%) for those retreated with ICIs combined with other agents. Two studies evaluated anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) retreatment. The ORR was 0–22.4%, the DCR was 50–72%, and the mOS was 4–21 months. The incidence of grade ⩾3 irAEs was 26–61%. Conclusion: Retreatment with ICIs is feasible for cancer patients considering its encouraging efficacy and tolerable safety. Further prospective trials are needed to explore more promising strategies and identify suitable populations for retreatment.

scholarly journals A real‐world data of Immune checkpoint inhibitors in solid tumors from India

2021 ◽  
Author(s):  
Vanita Noronha ◽  
George Abraham ◽  
Vijay Patil ◽  
Amit Joshi ◽  
Nandini Menon ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Real World Data ◽  
World Data
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