A first-in-human phase I study in patients with advanced and/or refractory solid malignancies to evaluate the safety of ATOR-1015, a CTLA-4 x OX40 bispecific antibody.
2020; Lippincott Williams & Wilkins; Volume: 38; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2020.38.15_suppl.3061
ISSN1527-7755
AutoresJeffrey Yachnin, Gustav Ullenhag, Ana Paula Carneiro, Dorte Nielsen, Kristoffer Rohrberg, Anne Månsson Kvarnhammar, Lena Schultz, Erika Bågeman, Camilla Wennersten, Charlotte Russell,
Tópico(s)Cancer Immunotherapy and Biomarkers
Resumo3061 Background: ATOR-1015 is a human CTLA-4 x OX40 targeting IgG1 bispecific antibody developed to be a next generation CTLA-4 antibody with enhanced immune activation and tumor-directed activity for improved efficacy and reduced toxicity. Methods: The primary objective of the study is to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) in patients with advanced solid malignancies. Safety and tolerability of ATOR-1015 are assessed by adverse events (AEs), vital signs, ECG, laboratory evaluations and physical examinations. Secondary objectives include pharmacokinetics (PK), immunogenicity and clinical efficacy. Clinical efficacy is assessed using Response Evaluation Criteria in Solid Tumors for immune-based therapeutics (iRECIST). The study is designed with single patient cohorts for doses below 100 mg followed by a modified 3+3 design (NCT03782467). Intra-patient dose escalation is allowed. ATOR-1015 is administered intravenously every other week as a single agent until confirmed progressive disease, unacceptable toxicity or withdrawal of consent. Results: From March 2019 to February 2020, 15 patients have been exposed to ATOR-1015. The median age of the patients is 52 years (range 40-72). The following cancer types have been included: colorectal cancer (n=8), uveal melanoma (n=2), pancreatic cancer (n=2), ovarian cancer (n=2), and cholangiocarcinoma (n=1). Patients received a median of 6 prior lines of therapy (range 3-16). Dose levels from 0.043 mg to 200 mg have been evaluated and declared safe. Dose escalation is ongoing, and 400 mg is under evaluation. The median time on study was 8 weeks (range 2.1-34.3). Four patients are on study and eleven patients have discontinued treatment . Reasons for discontinuation include clinical deterioration (n=7), death due to disease progression (n=2), confirmed disease progression (n=1) and investigator´s decision (n=1). Six of the 15 patients experienced drug-related AEs which were grade 2 or less. Infusion-related reactions (IRR) were reported in four patients. One of those four also had abdominal pain and mediastinal burning sensation. The IRR symptoms were predominantly rash. One patient had vitiligo, and one had rash. No dose-limiting toxicities have occurred. Preliminary PK data show dose-proportional kinetics up to 200 mg. Conclusions: The dosing of ATOR-1015 has been safe and well-tolerated up to 200 mg. Dose escalation continues and the current dose level under evaluation is 400 mg. Clinical trial information: NCT03782467 .
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