ABBV-181 is a humanized, recombinant, IgG1 monoclonal antibody targeting programmed cell death 1 (PD-1), incorporating an Fc mutation to limit FcgR-mediated effector function. Here we present preliminary ABBV-181 monotherapy data.
Patients (pts) with previously treated advanced solid tumors received ABBV-181 to progression at 1, 3, or 10 mg/kg IV Q2W (3 + 3 dose finding phase). Following dose finding, multi-histology, non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cohorts were opened. Dose limiting toxicities (DLTs) were assessed on days 1-28 of dose finding focused on immune mediated (IM) events, hemolysis, and cytopenia. Response is assessed Q8W per response evaluation criteria in solid tumors (RECIST v.1.1) and immune RECIST.
As of January 15, 2018, 53 pts were treated with ABBV-181: 25 in dose finding, 17, 6, and 5 in multi-histology, HNSCC and NSCLC cohorts, respectively. Median age was 61 (range 27-84) years, 41% male, most frequent diagnoses in dose finding and multi-histology: cholangio, ovarian, breast and cervical carcinoma. Median days on study were 43 (range 1-379), 42 (79%) pts had ≥ 1 adverse event (AE), 22 pts (42%) had grade ≥ 3 AEs and 8 (15%) pts had IM AEs. The most frequent AEs of any grade were: fatigue (18 pts), constipation and vomiting (9 pts each). No DLTs were reported. ABBV-181 was discontinued in 33 (62%) pts, 27 for progression and 1 each for AEs of diabetic ketoacidosis, progression and small intestinal obstruction. PD-L1 was expressed on 7/21 (33%) available pretreatment samples (Dako 28-8 assay with 1% threshold). By investigator assessment, 4/34 (12%) pts with post baseline assessment responded (all in dose finding, all partial responses). Sustained PD-1 saturation on circulating CD4 T cells was observed at all doses. ABBV-181 pharmacokinetics (PK) were approximately dose-proportional in dose finding.
ABBV-181 monotherapy demonstrates target engagement and encouraging efficacy without unexpected safety signals. PK and pharmacodynamic data from dose finding support flat doses of 250 mg Q2W, 375 mg Q3W or 500 mg Q4W for expansion. Enrollment in the expansion cohorts continues.
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P.A. Cassier: Honoraria: Novartis, Roche-Genentech, Blueprint Medicines, Amgen; Institution research funding: Novartis, Roche/Genentech, Lilly, Blueprint Medicines, Bayer, AstraZeneca, Celgene, Plexxikon, AbbVie, Bristol-Myers Squibb, Merck Serono, Merck, Sharp and Dohme. K. Peltola: Advisory fees: Orion Pharma, BMS, MSD, Pfizer, Ipsen and Roche; Stock holder: Faron Pharmaceuticals. A.I. Spira: Consultant and institutional research support: AbbVie. M.M.E. Tanner: Finnish advisory board: Roche, Novartis, Pfizer; Speakers bureau: Roche, Novartis, Pfizer, Amgen. D. Afar, S. Englert, A. Parikh, A. Reddy, G. Vosganian: Employee and may own stock: AbbVie. A.W. Tolcher: Consultant: AbbVie. All other authors have declared no conflicts of interest.