Extended phase I study of AS1411 in renal and non-small cell lung cancers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13098-13098 ◽  
Author(s):  
D. A. Laber ◽  
B. S. Taft ◽  
G. H. Kloecker ◽  
P. J. Bates ◽  
J. O. Trent ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Stable Disease ◽  
Peak Plasma ◽  
Small Cell ◽  
Post Treatment ◽  
Pharmacokinetic Analysis ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Nsclc Patients

13098 Background: AS1411 is an oligonucleotide aptamer that binds to nucleolin, a protein expressed on the surface of tumor cells. A dose-escalating phase I trial in patients with various advanced cancers revealed no serious toxicities and consequently did not reach an MTD. There was evidence of activity, especially in renal cell carcinoma (RCC). This study has been reopened for further dose escalation to reach an optimal biological dose (OBD; unless an MTD is reached) in patients with RCC and non-small cell lung cancer (NSCLC). Methods: Patients had advanced RCC or NSCLC refractory to standard treatment. AS1411 was administered as a single continuous 7-day iv infusion, with the option of a second cycle. Patients were enrolled in cohorts of 3. If no serious toxicity was observed within 28 days, the dose was escalated to the next level. Toxicity was graded using the NCI CTCAE v3.0. The study plan was to enroll additional patients at the OBD such that a total of 12 RCC and 12 NSCLC patients received a 7-day infusion. Blood and urine samples were taken for pharmacokinetic analysis. Tumor responses were assessed every 28 days using the RECIST guidelines. Results: No serious adverse events have been observed up to a dose of 22mg/kg/day, which was associated with a mean peak plasma concentration of 1.5 μM. Response findings to date are as follows: of 5 RCC patients, 1 maintains a near-complete response 18 months after treatment, 3 have ongoing stable disease (SD; 1 at 3 months, 2 at 2 months) and a fourth had progressive disease (PD) at 2 months post-treatment; of 3 NSCLC patients, 1 has an ongoing SD and 2 had PDs at 1 month post-treatment. Recruitment and follow up continues. Conclusions: A 7-day infusion of AS1411 at 22mg/kg/day was not associated with any serious adverse events and achieved peak plasma concentrations in the range at which killing of various cancer cell lines is observed in vitro. A single further escalation is planned to reach a dose of 40mg/kg/day. Observation of additional cases of stable disease in RCC supports the previous observations of anti-cancer effects in this disease. [Table: see text]

scholarly journals TARGETED THERAPY OF NON-SMALL-CELL LUNG CANCER PATIENTS: MOST COMMON ADVERSE EVENTS AND METHODS OF THEIR CORRECTIONS

2017 ◽  
Vol 22 (6) ◽  
pp. 300-306
Author(s):  
Elena V. Reutova ◽  
K. P Laktionov ◽  
M. S Ardzinba
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Long Term Treatment ◽  
Nsclc Patients

Major advances in the treatment of non-small-cell lung cancer (NSCLC) patients are associated with the targeted therapy. It is both highly effective in the presence of activating mutations in the tumor and generally well-tolerated. Serious adverse events are recorded much less than with chemotherapy. There are significant differences in the toxicity profile. Both early detection and proper and timely correction of complications of targeted therapies are necessary for the successful long-term treatment of metastatic NSCLC patients.

scholarly journals 25 Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A29-A29
Author(s):  
Leeseul Kim ◽  
Young Kwang Chae ◽  
Dong-Uk Lee
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Primary Immune Response ◽  
Small Cell Lung ◽  
Serum Proteome ◽  
Proteome Level ◽  
Nsclc Patients

BackgroundPredicting immune-related adverse events (irAEs) in early stage is being emphasized even more. Host response to disease is reflected in serum proteome level and that allows serum proteome level as a new marker to explore response to immunotherapy. With the help of a serum-based proteomics test, Primary Immune Response (PIR), we are accessing the correlations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients.MethodsData of 48 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsAmong the 48 NSCLC patients, 19 patients (39%) experienced one or more irAEs with the majority classified as either grade 1 (n=7, 36%) or grade 2 (n=10, 52%). PIR-sensitive group showed no difference in irAE free period compared to PIR-not sensitive (p=0.92, HR=0.95, 95% CI=00.3212 to 2.834). The median ‘Time to first irAE’ were undefined and 24 in PIR-sensitive and PIR-not sensitive, respectively.ConclusionsOur results demonstrated PIR-sensitive patients are not likely to tolerate immunotherapy longer without developing irAEs.

scholarly journals Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lea Daniello ◽  
Mariam Elshiaty ◽  
Farastuk Bozorgmehr ◽  
Jonas Kuon ◽  
Daniel Kazdal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Palliative Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Type ◽  
Nsclc Patients

IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

scholarly journals Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110458
Author(s):  
Mark A. Socinski ◽  
Cornelius F. Waller ◽  
Tazeen Idris ◽  
Igor Bondarenko ◽  
Alexander Luft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Double Blind

Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

Potential role of serum proteome in predicting immune-related adverse events from immune checkpoint inhibitors in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21218-e21218
Author(s):  
Leeseul Kim ◽  
Young Kwang Chae ◽  
Chan Mi Jung ◽  
Emma Yu ◽  
Alice Daeun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients

e21218 Background: Early recognition of immune-related adverse events (irAEs) of immune checkpoint inhibitors(ICI) is important. Circulating proteome reflects host response to diseases and is being explored as a marker for response to immunotherapy. We previously have reported that a serum-based proteomics test, Primary Immune Response (PIR) demonstrated a trend that PIR-sensitive patients are more likely to tolerate ICI treatment longer without developing irAEs in non-small cell lung cancer (NSCLC) patients. The VeriStrat test is another serum-based proteomic assay, which was reported to be predictive of survival outcomes for all treatment regimens and lines of therapy including ICI in NSCLC. We explored the associations between the VeriStrat test and developing irAEs in NSCLC patients treated with ICI. Methods: Data of 70 consented NSCLC patients treated with any regimens and lines of therapy including ICI were collected. Samples were grouped into either VeriStrat ‘Good’(VS-G) or VeriStrat ‘Poor’(VS-P). We analyzed the durations from the immunotherapy initiation to each episode of irAE and each irAE above grade 2 using log-rank test. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Among the 70 patients, 18 patients (25%) experienced one or more irAEs. There was no significant difference in ‘Time to first irAE’ between VS-G and VS-P (p = 0.72, HR = 0.82, 95% CI = 0.29-2.32). Among 48 VS-G patients, 12(25%) had one or more irAE and 5(10%)had irAE graded over 2. Among 22 VS-P patients, 6(27%) had one or more irAE and 2(9%) had irAE graded over 2. There was no significant difference between VS-G and VS-P groups in the development of irAE and irAE graded over 2. Conclusions: There was no statistically significant association between the VeriStrat test and the development of irAEs. Further studies are warranted to investigate proper serum based proteomic assay to predict the development of irAE.

Sign in / Sign up

Export Citation Format

Share Document