Abstract 975TiP
Background
Stimulation of the immune system to generate antitumor response represents a compelling therapeutic strategy, especially in settings where only some patients (pts) achieve response. ABBV-368 is a novel, immunoglobulin G1 anti-OX40 monoclonal antibody agonist that elicits tumor responses by stimulating effector T cells and inhibiting regulatory T cells (Le Tourneau et al. SITC. 2019;432). Tilsotolimod is a synthetic TLR9 agonist with immunostimulatory activity (Babiker et al. AACR. 2020;134). Budigalimab (ABBV-181) is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting PD-1 modified to reduce Fc receptor interactions and limit effector function. This phase Ib, multicenter, open-label study (NCT04196283) is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ABBV-368 in combination with tilsotolimod and other agents (± nab-paclitaxel and budigalimab) in pts with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCC).
Trial design
Pts ≥18 years with histologically confirmed SCC (of the oral cavity, oropharynx, larynx, or hypopharynx) with ≥1 lesion accessible for intratumoral (IT) injection, are eligible. Pts must have an ECOG performance status of 0 or 1, a life expectancy of ≥3 months, received 1 prior immunotherapy regimen (including a PD-(L)1 inhibitor), and have ≤3 prior treatments in the R/M setting. Pts with uncontrolled CNS metastases and those who have received prior OX40 or TLR agonist treatment (excluding topical agents) are ineligible. Pts in Arm 1 will receive intravenous (IV) ABBV-368 plus tilsotolimod (IT); pts in Arm 2, ABBV-368 + tilsotolimod + IV nab-paclitaxel; and pts in Arm 3, ABBV-368 + tilsotolimod + nab-paclitaxel and IV budigalimab. Primary objectives are to assess safety, tolerability, and pharmacokinetics of these combinations. Secondary objectives are to assess objective response rate, clinical benefit rate, time to response, progression-free survival, and duration of response. Paired biopsy samples will be taken for exploratory analysis. Planned enrollment is 69 pts.
Clinical trial identification
NCT04196283.
Editorial acknowledgement
Medical writing support was provided by Devon Roll, PhD, of Bio Connections, LLC.
Legal entity responsible for the study
AbbVie, Inc.
Funding
AbbVie, Inc. funded this study.
Disclosure
X. Le: Advisory/Consultancy, Consultant/advisory fees: Eli Lilly; Research grant/Funding (self), research funding: Eli Lilly; Advisory/Consultancy, Consultant/advisory fees: AstraZeneca; Advisory/Consultancy, Consultant/advisory fees: EMD Serono; Research grant/Funding (self), research funding: Boehringer Ingelheim; Research grant/Funding (self), research funding: Spectrum Pharmaceuticals. C. Maurice-Dror: Speaker Bureau/Expert testimony, Speakers’ bureau participation: Bristol-Myers Squibb (BMS); Speaker Bureau/Expert testimony, Speakers’ bureau participation: MSD; Speaker Bureau/Expert testimony, Speakers’ bureau participation: Medison. K. Gold: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Rakuten; Advisory/Consultancy: Takeda; Advisory/Consultancy: Regeneron. M. Nagasaka: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi-Sankyo; Advisory/Consultancy: Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Caris Life Sciences; Research grant/Funding (self): Tempus. I. Moreno: Speaker Bureau/Expert testimony: Bristol-Myers Squibb. M. McDevitt, M. Patel, D. Da Costa, S. Lambert, Y. Li M. Blaney: Full/Part-time employment, Employment with AbbVie and may own AbbVie stock or stock options: AbbVie. All other authors have declared no conflicts of interest.