Abstract 1028TiP
Background
PD-(L)1 inhibitors provide durable clinical benefit for some patients with various tumors; however, combination immune therapy may be needed to optimize outcomes. T-cell Immunoglobulin and ITIM domain (TIGIT), expressed on activated T and natural killer (NK) cells, inhibits antitumor immunity upon binding CD155 on tumors. AB308, an anti-TIGIT humanized IgG1 monoclonal antibody (mAb) with functional FcR binding, reverses TIGITCD155-mediated T-cell inhibition in preclinical models. ARC-12 will assess if AB308-mediated TIGIT pathway blockade augments zimberelimab (zim; anti-PD-1 mAb) activity.
Trial design
This is a first-in-human, open-label study of AB308 + zim in pts with advanced malignancies. For the dose-escalation, pts must have solid tumors without a standard-of-care therapy or relapsed/refractory (R/R) NHL; ≥1 measurable lesion; and ECOG performance score 0-1. AB308 + zim will be given intravenously (IV) once every 3 weeks (Q3W; Part A) or 4 weeks (Q4W; Part B; Table). In Part A, Cohort 1 will follow 3+3+6 rules and allow AB308 dose adjustment if dose-limiting toxicities (DLTs) warrant; all other dose-escalation cohorts will use 3+3 rules. Upon Cohort 2 DLT period completion, Part B will begin enrollment independently and in parallel to Part A. A recommended dose for expansion (RDE) for AB308 + zim may be identified for both Q3W and Q4W schedules. In the dose-expansion, disease-specific cohorts will be enrolled (Table); all pts in each cohort will receive AB308 + zim at either Q3W or Q4W. For both the dose-escalation and dose-expansion, the primary endpoints assess safety and tolerability of AB308 + zim; secondary endpoints include pharmacokinetics, immunogenicity, and objective response rate for AB308 + zim. Additional secondary endpoints in the dose-expansion are disease control rate and duration of response. ARC-12 is actively recruiting in the USA (NCT04772989). Table: 1028TiP
Dose-Escalation and Dose-Expansion are both section headers and should match in format/style please
| Dose-Escalation | |
| Part A, Cohorts 1–3 | 3 escalating doses of AB308 IV Q3W +360 mg zim IV Q3W |
| Part B, Cohorts 4–6 | 3 escalating doses of AB308 IV Q4W +480 mg zim IV Q4W |
| Dose-Expansion | |
| Cohort 1: 1L PD-L1-high non-small cell lung cancer (TPS ≥50%) | AB308 + zim combo RDE IV Q3W or Q4W |
| Cohort 2: 2L+ R/R melanoma;PD-(L)1-experienced | |
| Cohort 3: 2L+ gastric/gastroesophageal junction (CPS ≥1) or esophageal cancer (CPS ≥10) | |
| Cohort 4: 2L+ cervical cancer (CPS ≥1) | |
| Cohort 5: 3L+ R/R diffuse large B-cell lymphoma or 4L+ R/R multiple myeloma |
Clinical trial identification
NCT04772989.
Editorial acknowledgement
Medical writing assistance was provided by Amanda Martin, PhD, of Medical Expressions (Chicago, IL) and was funded by Arcus Biosciences.
Legal entity responsible for the study
Arcus Biosciences, Inc.
Funding
Arcus Biosciences, Inc.
Disclosure
M.A. Mckean: Financial Interests, Institutional, Research Grant: Acentage Pharma Group; Financial Interests, Institutional, Research Grant: Bicycle Therapeutics; Financial Interests, Institutional, Research Grant: Dragonfly Therapeutics; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: IDEAYA Biosciences; Financial Interests, Institutional, Research Grant: Ikena Oncology; Financial Interests, Institutional, Research Grant: Infinity Pharmaceuticals; Financial Interests, Institutional, Research Grant: Jacobio Pharmaceuticals; Financial Interests, Institutional, Research Grant: Moderna; Financial Interests, Institutional, Research Grant: NBE Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Oncorus; Financial Interests, Institutional, Research Grant: Plexxikon; Financial Interests, Institutional, Research Grant: Prelude Therapeutics; Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sapience Therapeutics; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Tizona Therapeutics; Financial Interests, Institutional, Research Grant: Tmunity Therapeutics; Financial Interests, Institutional, Research Grant: TopAlliance Biosciences; Financial Interests, Institutional, Advisory Role: Array BioPharma; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: MedPage Today; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Regeneron Pharmaceuticals. P. Foster: Financial Interests, Personal, Full or part-time Employment: Arcus; Financial Interests, Personal, Stocks/Shares: Arcus. C. Trudeau: Financial Interests, Personal, Full or part-time Employment: Arcus; Financial Interests, Personal, Stocks/Shares: Arcus. M. Scharville: Financial Interests, Personal, Full or part-time Employment: Arcus; Financial Interests, Personal, Stocks/Shares: Arcus. A. El-Baghdady: Financial Interests, Personal, Full or part-time Employment: Arcus; Financial Interests, Personal, Stocks/Shares: Arcus. A. Patnaik: Financial Interests, Personal, Other, Honoraria: Texas Society of Clinical Oncology; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Livzon; Financial Interests, Institutional, Research Grant: Klus Pharma; Financial Interests, Institutional, Research Grant: Fochon Pharmaceuticals; Financial Interests, Institutional, Research Grant: Plexxikon; Financial Interests, Institutional, Research Grant: Corvus Pharmaceuticals; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: Infinity Pharmaceuticals; Financial Interests, Institutional, Research Grant: Ionova; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Surface Oncology; Financial Interests, Institutional, Research Grant: Upsher-Smith; Financial Interests, Institutional, Research Grant: Arcus Ventures; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Symphpgen; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Tesaro; Financial Interests, Institutional, Research Grant: Forty Seven; Financial Interests, Institutional, Research Grant: Bolt Biotherapeutics; Financial Interests, Institutional, Research Grant: Pieris Pharmaceuticals; Financial Interests, Institutional, Research Grant: Vigeo Therapeutics; Financial Interests, Institutional, Research Grant: Syndax; Financial Interests, Institutional, Research Grant: Seattle Genetics. All other authors have declared no conflicts of interest.