Dose escalation and expansion phase I studies with the tumour-targeting antibody-tumour necrosis factor fusion protein L19TNF plus doxorubicin in patients with advanced tumours, including sarcomas

2021 ◽  
Vol 150 ◽  
pp. 143-154
Author(s):  
Christoph Schliemann ◽  
Teresa Hemmerle ◽  
Andrew F. Berdel ◽  
Linus Angenendt ◽  
Andrea Kerkhoff ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Phase I ◽  
Tumour Necrosis Factor ◽  
Dose Escalation ◽  
Tumour Necrosis ◽  
Tumour Targeting ◽  
Expansion Phase ◽  
Phase I Studies ◽  
Necrosis Factor

THU0373 SECUKINUMAB DOSE ESCALATION ON ACR RESPONSES IN ANTI-TUMOUR NECROSIS FACTOR NAÏVE PATIENTS WITH PSORIATIC ARTHRITIS: 2-YEAR DATA FROM THE PHASE 3 FUTURE 4 AND FUTURE 5 STUDIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 418.1-419
Author(s):  
P. Emery ◽  
M. Ǿstergaard ◽  
L. C. Coates ◽  
A. Deodhar ◽  
E. Quebe-Fehling ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Psoriatic Arthritis ◽  
Tumour Necrosis Factor ◽  
Dose Escalation ◽  
Tumour Necrosis ◽  
Research Support ◽  
Phase 3 ◽  
Post Dose ◽  
Link Type ◽  
Necrosis Factor

Background:Secukinumab (SEC) 150 and 300 mg doses are approved for the treatment of psoriatic arthritis (PsA). SEC 300 mg is the recommended dose for patients (pts) with concomitant moderate-to-severe plaque psoriasis or who are anti-tumour necrosis factor (TNF) inadequate responders. An increase from 150 mg to 300 mg has been reported to be beneficial in some patients with a suboptimal response to SEC 150 mg.1Here, we present a post hoc analysis in anti-TNF naïve pts who escalated from SEC 150 to 300 mg dose in two Phase 3 studies, FUTURE 4 (NCT02294227) and FUTURE 5 (NCT02404350).Objectives:To evaluate the clinical efficacy on joints following dose escalation from SEC 150 to 300 mg on ACR responses in anti-TNF naïve pts with PsA.Methods:Study design, patient inclusion and exclusion criteria of the FUTURE 4 and FUTURE 5 studies have been reported previously.1–3In FUTURE 4, 341 pts were randomised in a 1:1:1 ratio to SEC 150 mg with loading dose (LD), SEC 150 mg without LD, or placebo. In FUTURE 5, 996 pts were randomised in a 2:2:2:3 ratio to SEC 300 mg with LD, SEC 150 mg with LD, SEC 150 mg without LD or placebo. Following a protocol amendment, pts were allowed to escalate from 150 mg to the 300 mg dose, in the event of suboptimal response based on investigator’s judgment, starting at Week 36 in FUTURE 4 and at Week 52 in FUTURE 5. ACR responses in anti-TNF naïve pts were evaluated pre- and up to 32 and 40 weeks post-escalation, in FUTURE 4 and FUTURE 5, respectively: pts were grouped into four ranges based on their response: no (< 20); low (≥ 20 to < 50); moderate (≥ 50 to < 70); high (≥ 70) ACR responses. Data presented are as observed in the Sankey-style overlay plot.Results:Dose escalation from SEC 150 to 300 mg occurred in 136 pts in FUTURE 4 and in 236 pts in FUTURE 5. The proportion of ACR responders increased and the proportion of non-responders decreased in anti-TNF naïve pts who escalated from SEC 150 to 300 mg in the two studies. The proportion of anti-TNF naïve pts with a response ≥ACR50 increased from 20% to 41% in FUTURE 4 and 28% to 46% in FUTURE 5, post dose escalation. The ACR responses in anti-TNF naïve pts up to 40 weeks after escalation from SEC 150 to 300 mg are presented in the Sankey-style overlay (Figure).Figure.ACR Response bar chart with Sankey-style overlays up to 40 weeks, after dose escalation from SEC 150 mg to 300 mg, in anti-TNF naïve pts in FUTURE 4 and 5Conclusion:The proportion of ACR responders increased within 12-16 weeks and was sustained up to 40 weeks following dose escalation in anti-TNF naïve pts with PsA. These results suggest that dose escalation from SEC 150 to 300 mg may be beneficial in anti-TNF naïve pts with a suboptimal response on SEC 150 mg.References:[1]Kivitz AJ, et al. Rheumatol Ther. 2019;6(3):393–407;[2]Mease PJ, et al. Ann Rheum Dis. 2018;77:890–7;[3]Mease, P.J., et al. ACR Open Rheumatology. 2019 [ePub ahead of print] doi:10.1002/acr2.11097.Disclosure of Interests:Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Laura C Coates: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Erhard Quebe-Fehling Shareholder of: Novartis, Employee of: Novartis, Pascale Pellet Shareholder of: Novartis, Employee of: Novartis, Luminita Pricop Shareholder of: Novartis, Employee of: Novartis, Corine Gaillez Shareholder of: Novartis, Employee of: Novartis, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB

A phase I study of local treatment of liver metastases with recombinant tumour necrosis factor

1992 ◽  
Vol 28 (6-7) ◽  
pp. 1073-1078 ◽  
Author(s):  
George P. van der Schelling ◽  
Jan N.M. Ijzermans ◽  
Tjebbe C. Kok ◽  
Marcel Scheringa ◽  
Richard L. Marquet ◽  
...  
Keyword(s):  
Phase I ◽  
Liver Metastases ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Phase I Study ◽  
Local Treatment ◽  
Necrosis Factor
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