Abstract 560P
Background
Antagonists of IAPs regulate apoptosis and modulate NF-κB signaling which drives the expression of genes involved in immune and inflammatory responses. In pt tumors Debio 1143 increased PD-1/PD-L1 expression and tumor infiltrating lymphocyte counts and in pre-clinical models synergized with the anti-tumor activity of PD-1/PD-L1 checkpoint inhibitors. The aim of this study is to assess the safety and efficacy of Debio 1143 in combination with nivolumab, an anti-PD-1 antibody, in patients (pts), with advanced solid tumors, previously treated with anti-PD-1/PD-L1 treatment.
Methods
In phase Ib, the primary objective was to determine the recommended phase II dose (RP2D) of Debio 1143 in combination with nivolumab. Overall safety/tolerability, antitumor activity (per RECIST 1.1) and pharmacokinetics (PK) were secondary endpoints. Pts who had received at least one line of prior systemic treatment and progressed/relapsed during/after anti-PD-1/PD-L1 therapy were eligible. Dose selection was guided by a classical 3+3 design.
Results
At data cut-off (6th March 2020) 11 pts were treated in phase Ib, 2 dose levels were evaluated for Debio 1143; 150 (n=3) and 200 (n=8) mg/d (10-days on/4-days off) combined with nivolumab 240 mg q2w. Pts: ECOG PS 0 (64%) or 1 (36%), 82% male, median age 60 years, colorectal (n=4), head and neck (n=4) and other (n=3) cancers. Median duration of exposure was 11.6 weeks. Eight (73%) pts discontinued treatment due to; disease progression (6, 55%) patient decision (1, 9%) and adverse event (AE) unrelated to study drug (1, 9%). No dose limiting toxicities were reported and no Gr ≥3 drug-related AEs occurred. PK dispositions for Debio 1143 and nivolumab were in line with previous studies. The unconfirmed overall response rate was 18%; unconfirmed partial responses in 2 pts (18%) (colorectal and gastric cancers) and stable disease in 4 pts (36%).
Conclusions
Oral Debio 1143 in combination with nivolumab was well tolerated, all AEs were manageable and preliminary antitumor efficacy was observed. This study is ongoing at the RP2D (Debio 1143 at 200 mg/d plus nivolumab 240 mg q2w) to further establish antitumor activity during phase II.
Clinical trial identification
Protocol ID: Debio 1143-106. NCT04122625.
Editorial acknowledgement
Doctor Shaun Villa from Cancer Communications and Consultancy Ltd Knutsford UK provided editorial assistance.
Legal entity responsible for the study
Debiopharm International S.A.
Funding
Debiopharm International S.A.
Disclosure
A.B. Azaro Pedrazzoli: Advisory/Consultancy: Orion Pharma; Advisory/Consultancy: Amcure GmbH. V. Moreno: Advisory/Consultancy: BMS; Advisory/Consultancy: Pieris; Advisory/Consultancy: Bayer; Advisory/Consultancy: Janssen. C.A. Gomez-Roca: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Speaker Bureau/Expert testimony: Pierre Fabre; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Erytech; Advisory/Consultancy: Guidepoint; Advisory/Consultancy: GLG; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy: Novartis; Non-remunerated activity/ies: FITC; Non-remunerated activity/ies: ESMO. C. Even: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Innate Pharma; Advisory/Consultancy: Merck Serono. P. Cassier: Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Innate Pharma; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Molecular Partner; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Toray; Research grant/Funding (institution): Transgene. M. de Miguel: Research grant/Funding (self): MSD; Research grant/Funding (self): Roche; Research grant/Funding (self): Pharmamar; Research grant/Funding (self): Sanofi; Research grant/Funding (self): Novartis; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Sanofi; Research grant/Funding (self): Array. D. Purcea: Full/Part-time employment: Debiopharm. K. Gollmer: Full/Part-time employment: Debiopharm. C. Riff: Full/Part-time employment: Debiopharm. S.A. Szyldergemajn: Full/Part-time employment: Debiopharm. E. Calvo: Honoraria (self): Debiopharm; Honoraria (self): Astellas; Honoraria (self): Novartis; Honoraria (self): Nanobiotix; Honoraria (self): Pfizer; Honoraria (self): Janssen-Cilag; Honoraria (self): GLG; Honoraria (self): PsiOxus Therapeutics; Honoraria (self): Merck; Honoraria (self): Medscape; Honoraria (self): BMS; Honoraria (self): Gilead; Honoraria (self): Seattle Genetics; Honoraria (self): Pierre Fabre; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Cerulean Pharma; Honoraria (self): EUSA; Honoraria (self): Gehrmann Consulting; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Guidepoint; Honoraria (self): Servier; Honoraria (self): Celgene; Honoraria (self): AbbVie; Honoraria (self): Amcure; Honoraria (self): OncoDNA; Leadership role: START Madrid; Shareholder/Stockholder/Stock options: START, Oncoart Associated ; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): ACEO. All other authors have declared no conflicts of interest.