scholarly journals Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Relinde I. Y. Lieverse ◽  
Evert J. Van Limbergen ◽  
Cary J. G. Oberije ◽  
Esther G. C. Troost ◽  
Sine R. Hadrup ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Standard Of Care ◽  
Open Label ◽  
Stereotactic Ablative Body Radiotherapy ◽  
Open Label Phase ◽  
Randomised Controlled ◽  
Nsclc Patients

Randomized phase II study of nivolumab (N) alone versus with pegilodecakin (PEG) in combination with N in patients (pts) with post-platinum immunotherapy-naive stage IV non-small cell lung cancer (NSCLC) and no or low PD-L1 expression (CYPRESS 2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21744-e21744
Author(s):  
Robert M. Jotte ◽  
Jerome H. Goldschmidt ◽  
Jeffrey Gary Schneider ◽  
Merrill Kingman Shum ◽  
David Berz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Smoking History ◽  
Prior History ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Open Label Phase ◽  
History Of ◽  
Secondary Endpoints

e21744 Background: Nivolumab (N) is an immune checkpoint inhibitor (CPI) approved to treat post-platinum NSCLC as monotherapy. PEG in combination with N has demonstrated promising efficacy in NSCLC pts in a phase I trial (IVY; NCT02009449; Naing et al., 2019 Lancet Oncol), providing rationale for this randomized phase II trial (CYPRESS 2). Methods: CYPRESS 2 was an open label phase II trial, for ECOG 0-1, PD-L1 negative or low (TPS 0-49%), Stage IV NSCLC pts, without known EGFR/ALK mutations. Pts were randomized 1:1 to arm N (240 mg every 14-days or 480 mg every 28-days as decided by investigator) v. arm PEG+N (received N as above + PEG daily of 0.8 mg if weight ≤80kg and 1.6mg if weight > 80 kg). Pts were stratified by tumor histology and smoking history and must have no prior history of cancer or CPI therapy. Primary endpoint was ORR (per RECIST v 1.1 per investigator). Secondary endpoints included PFS, OS, and safety. Exploratory endpoints included immune activation biomarkers (baseline and change from baseline), assessed by immunoassay. Results: As of Aug 28, 2019, 52 pts were randomized to PEG+N (n=27) or N (n=25). Median follow-up time was 11.6 months. The following results were found for PEG+N versus N: ORR 14.8% v. 12.0%, mPFS 1.9 v. 1.9 months with HR = 1.01 (95% CI [0.52, 1.95]), mOS 6.7 v. 10.7 months with HR = 1.87 (95% CI [0.77, 4.53]). Gr ≥3 treatment related adverse events (TRAEs) for PEG+N versus N were 70.4% vs. 16.7%. Gr 3 TRAEs of ≥10% incidence included anemia (40.7% v. 0%), fatigue (18.5% v. 0%), and thrombocytopenia (14.8% v. 0%). In PEG+N arm, increased circulating IL-18, Granzyme B, FasL, and IFNg levels and decreased TGFb levels were observed on treatment. Conclusions: Exploratory pharmacodynamic results were consistent with immunostimulatory signals of the IL-10R pathway. Despite evidence of biological effect, adding PEG to N did not lead to improvement in ORR, PFS, or OS in post-platinum advanced NSCLC with no or low PD-L1 expression. PEG+N arm demonstrated expected safety profile but overall higher toxicity compared to nivolumab alone. Clinical trial information: NCT03382912.

Randomized phase II study of pembrolizumab (P) alone versus pegilodecakin (PEG) in combination with P as first-line (1L) therapy in patients (pts) with stage IV non-small cell lung cancer (NSCLC) with high PD-L1 expression (CYPRESS 1).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9563-9563
Author(s):  
David R. Spigel ◽  
Merrill Kingman Shum ◽  
Jeffrey Gary Schneider ◽  
Robert M. Jotte ◽  
Jennifer L. Eisenstein ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Stage Iv ◽  
Prior History ◽  
P Value ◽  
Open Label ◽  
Randomized Phase Ii ◽  
Open Label Phase ◽  
Treatment Naïve

9563 Background: Pembrolizumab (P) is an immune checkpoint inhibitor (CPI) approved to treat 1L advanced NSCLC pts with high PD-L1 expression. PEG + CPI has demonstrated promising efficacy in NSCLC pts in a phase I trial (IVY; NCT02009449; Naing et al., 2019 Lancet Oncol), providing rationale for this randomized phase II trial (CYPRESS 1; NCT03382899). Methods: CYPRESS 1 was an open label phase II trial, for treatment-naïve, ECOG 0-1, PD-L1 high (22C3 clone TPS ≥ 50%), Stage IV NSCLC pts, without known EGFR/ALK mutations. Pts were randomized 1:1 to arm P (received 200mg IV on day 1 of a 21-day cycle) v. arm PEG+P (received P as above + PEG daily of 0.8 mg if weight ≤80kg and 1.6mg if weight> 80 kg up to 35 cycles in each arm). Pts were stratified by tumor histology and must have no prior history of cancer or prior CPI therapy. Primary endpoint was ORR (per RECIST v1.1 by investigator) Secondary endpoints included PFS, OS, and safety. Exploratory endpoints included ORR and PFS by blinded independent central review (BICR). Immune activation biomarkers (baseline and change from baseline) were assessed by serum immunoassay, IHC, and sequencing. Results: As of Dec 6, 2019, 101 pts were randomized to PEG+P (n=51) or P (n=50). Median follow-up time was 10.0 months (95% CI [8.4, 11.1]). Results for PEG+P versus P were: ORR per investigator was 47% v. 44% (p=0.76), ORR per BICR was 53% v. 46%(p=0.78), mPFS per investigator was 6.3 v. 6.1 months with HR = 0.94 (95% CI [0.54, 1.63];p=0.82), mPFS per BICR was 6.4 v. 7.2 months with HR = 1.10 (95%CI [0.62, 1.96]; p=0.74), and mOS was 16.3 months v. not reached with HR = 1.36 (95% CI [0.66, 2.77]; p-value=0.40). Gr ≥3 treatment related adverse events (TRAEs) were 62% for PEG+P versus 19% for P. Gr ≥3 TRAEs with ≥10% incidence included anemia (20% vs. 0%) and thrombocytopenia (12% vs. 2%). Biomarker data on immunostimulatory signals of the IL-10R pathway will be included. Conclusions: Adding PEG to P did not lead to improvement in ORR, PFS, or OS, in 1L advanced NSCLC with high PD-L1 expression. PEG+P arm demonstrated expected safety profile but overall higher toxicity compared to pembrolizumab alone. Clinical trial information: NCT03382899 .

A randomised, open-label phase II trial of afatinib versus cetuximab in patients with metastatic colorectal cancer

2014 ◽  
Vol 50 (18) ◽  
pp. 3136-3144 ◽  
Author(s):  
Tamas Hickish ◽  
Jim Cassidy ◽  
David Propper ◽  
Ian Chau ◽  
Stephen Falk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Open Label ◽  
Open Label Phase

scholarly journals Capecitabine plus Oxaliplatin as a Second-Line Therapy for Advanced Biliary Tract Cancers: A Multicenter, Open-Label, Phase II Trial

2019 ◽  
Vol 10 (25) ◽  
pp. 6185-6190
Author(s):  
Seung Tae Kim ◽  
Sung Yong Oh ◽  
Jeeyun Lee ◽  
Jung Hun Kang ◽  
Hyun Woo Lee ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Second Line ◽  
Open Label ◽  
Second Line Therapy ◽  
Biliary Tract Cancers ◽  
Line Therapy ◽  
Open Label Phase

scholarly journals A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial

Trials ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Timothy Devos ◽  
Tatjana Geukens ◽  
Alexander Schauwvlieghe ◽  
Kevin K. Ariën ◽  
Cyril Barbezange ◽  
...  
Keyword(s):  
Treatment Group ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Active Treatment ◽  
Standard Of Care ◽  
Active Treatment Group ◽  
Proof Of Concept ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

Abstract Background The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. Methods DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. Discussion This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. Trial registration ClinicalTrials.govNCT04429854. Registered on 12 June 2020 - Retrospectively registered.

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