Abstract 988P
Background
Immuno-oncology drug nivolumab binds to T-cell PD-1 receptor and overcomes tumor induced inhibition of T-cell proliferation and cytokine release caused by PD-L1/2 interaction. It so enhances the immune system’s natural tumor erasing capacity. In combination with selective targeting of oncogenic signaling pathways by receptor tyrosine kinase inhibitor lenvatinib, a markedly improved response rate is expected in patients suffering from advanced stage HCC.
Methods
The investigator-initiated phase II single-armed trial comprises two successive Safety Run-in Phase (SRP) cohorts, each consisting of 3 consecutively recruited patients, to evaluate safety of defined dose level 0: 240 mg nivolumab i.v. q2w along with 12 mg (≥ 60 kg bw) resp. 8 mg (< 60 kg bw) lenvatinib p.o. qd. Primary endpoints are efficacy (ORR acc. to investigator assessed RECIST 1.1) and safety of combination treatment. 50 patients are planned in total. Up to now, 21 patients have been enrolled. This abstract focuses on safety data from SRP cohort 1 and 2 (6 patients) in which all AEs were evaluated after patients received 2 cycles of IMP in dose level 0.
Results
Summarized over both SRP cohorts, no dose limiting toxicities i.e. selected grade 4 events occurred. 2 SAEs (abdominal infection; not IMP-related; grade 3 / fever; IMP-related; grade 1) and 21 AEs have been documented (most common AEs: hypertension [3x (14%); IMP-related], pain [3x (14%) (flank; extremity; unspecified); not IMP-related] - in total 12 AEs IMP-related and 9 AEs not IMP-related). No grade 5 AE, one grade 4 AE (AST increase; IMP-related) and three grade 3 AEs (Abdominal infection and hepatic encephalopathy; not IMP-related / ALT increase; IMP-related) in two patients have been reported. All other AEs were of grades 1 or 2. No patient discontinued treatment during SRP.
Conclusions
Combination treatment with nivolumab 240 mg and lenvatinib 12/8 mg was assessed as safe and well tolerated from the data obtained from 6 patients in two cohorts, each received two combination cycles. Regular recruitment was thus opened in January 2020 and is planned to be completed in Q3/2020.
Clinical trial identification
NCT03841201; EudraCT: 2018-001480-23.
Editorial acknowledgement
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH.
Funding
EISAI GmbH, Bristol-Myers Squibb GmbH & Co. KGaA.
Disclosure
E. De Toni: Research grant/Funding (institution): Arquel; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): Bayer; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Eisai; Honoraria (self): Pfizer; Honoraria (self): Ipsen. G.M. Siegler: Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Sanofi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Lilly. M. Schultheiss: Honoraria (self): Falk Foundation e.V.; Advisory/Consultancy: Bayer Healthcare; Advisory/Consultancy: Bristol Myers Squibb. M. Geißler: Honoraria (self), Research grant/Funding (institution): Amgen; Honoraria (self): Bayer; Honoraria (self): Lilly; Honoraria (self): Merck; Honoraria (self): BMS; Honoraria (self): Celgene. S-E. Al-Batran: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme; Leadership role, Shareholder/Stockholder/Stock options: Institut für Klinische Krebsforschung IKF GmbH; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau/Expert testimony: MCI Group; Speaker Bureau/Expert testimony: promedicis; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid; Research grant/Funding (self): German Resarch Foundation; Research grant/Funding (self): Federal Ministry of Education and Research of Germany; Research grant/Funding (self): Vifor Pharma. All other authors have declared no conflicts of interest.