Abstract 4761
Background
ABBV-368 is a novel humanized IgG1 agonist monoclonal antibody specific for human OX40, a TNF receptor superfamily member expressed on activated and memory T-cell subsets, as well as T regulatory cells. The proposed ABBV-368 therapeutic mechanism of action includes activation of T effector cells and inhibition of the suppressive capacity of T regulatory cells. This ongoing first-in-human, phase 1, two-part study (NCT03071757) is investigating the safety, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of ABBV-368 in patients (pts) with advanced solid tumors.
Methods
Eligible pts include adults (≥18 years) with advanced or metastatic solid tumors. ABBV-368 was administered intravenously in a 3 + 3 dose-escalation design at doses ranging from 0.01 to 3.0 mg/kg every 2 weeks (4 cohorts). PK was assessed in cycle 1 and cycle 3. OX40 receptor saturation, Ki67 proliferation marker expression in peripheral blood immune cell subsets, and additional PD biomarkers were evaluated.
Results
As of Feb 12, 2018, 38 pts with advanced or metastatic tumors were enrolled in dose-escalation cohorts. Median age was 65 years (range, 38–78). No dose-limiting toxicities were reported during dose escalation. Overall, 15 (39.5%) pts reported grade (Gr) ≥3 treatment-emergent adverse events (TEAEs). Three (7.9%) pts reported Gr ≥ 3 TEAEs related to ABBV-368. Two investigator-reported immune-related AEs were documented, including hypothyroidism; neither were serious. ABBV-368 PK was approximately dose-proportional from 0.1- to 3-mg/kg doses during cycle 1, with dose-dependent target saturation. Initial antitumor activity has been observed. Updated safety, PK, PD, and efficacy data will be reported.
Conclusions
ABBV-368 was well tolerated; a maximum tolerated dose was not reached. Antitumor activity was observed at doses predicted to be biologically active. Further evaluation of ABBV-368 is ongoing in pts with advanced solid tumors.
Clinical trial identification
NCT03071757.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Editorial Acknowledgement
Medical writing support was provided by Mary L. Smith, PhD, CMPP, from TRM Oncology, Atlanta, GA, and funded by AbbVie.
Disclosure
A. Spira: Consultant and Institutional research support: AbbVie. A. Patnaik: Research grants to institution: Merck & Co., Inc. LG; Advisory board member: Merck & Co., Inc., AstraZeneca, AbbVie, Pfizer, Genentech/Roche; Research grant: Bristol-Myers Squibb. A.W. Tolcher: Consultant: AbbVie. M.E. Blaney, A. Parikh, A. Reddy, W. Henner, M. McDevitt, D. Afar: Employee and may own stock: AbbVie. J. Powderly: Employee and leadership role: Carolina BioOncology Institute PLLC; Stock/ownership: Iovance, Juno, Bluebird Bio, Kite Pharma, ZioPharm; Speaker bureau: Genentech, Bristol-Myers Squibb, Merck; Research funding: AstraZeneca, Genentech, Clovis, Corvus, Incyte, AbbVie, Bristol-Myers Squibb, MacroGenics; Patent or intellectual property: Founder of BioCytics, developing T-cell immunotherapies. All other authors have declared no conflicts of interest.
Resources from the same session
3816 - A prediction panel with DNA methylation biomarkers for lung adenocarcinoma
Presenter: Nan Shen
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5242 - Novel genomic classifier for early stage colorectal cancer patients
Presenter: Elisabeth Letellier
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5404 - Baseline Blood Immune Profiling to Predict Response to antiPD-1 in Patients with Advanced Non-Small Cell Lung Cancer
Presenter: Emanuela Romano
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5462 - Evaluation of clinicopathological and molecular criterias for screening of exonucleasic domain POLE (edPOLE) mutated patients in proficient Mismatch Repair (pMMR) colorectal and endometrial cancers.
Presenter: Justine Cohen
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5465 - Immune prognostic index (IPI) and Hyper-Progressive disease (HPD) in patients (pts) exposed to targeted agents (TAs) in Phase 1 trials (Ph1T): can lessons from immune checkpoint inhibitors (ICIs) be translated to other scenarios?
Presenter: Ignacio Matos Garcia
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5742 - Combination of baseline LDH, performance status and age to identify solid tumor patients with higher probability of response to anti-PD1 and PDL1 monoclonal antibodies
Presenter: Maria Silvia Cona
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5790 - Effects of concomitant genetic alterations on cancer patient overall survival
Presenter: Yu Wang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5144 - Circulating Exosomal Integrin _v_5 Predicts Liver Metastasis and Prognosis in Human Colorectal Cancer
Presenter: Dake Chu
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5149 - Circulating and tumor-associated caspase-4: a novel diagnostic and prognostic biomarker for Non-Small Cell Lung Cancer patients?
Presenter: Rosalinda Sorrentino
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5673 - Smokers and COPD patients have high circulating caspase-4 levels: is it an alarm?
Presenter: Michela Terlizzi
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract