Reference Detail

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Abstract

PMID

Authors

Kristoffer Staal Rohrberg, Mariana Brandão, Eduardo Castanon Alvarez, Enriqueta Felip, Eelke Hiddo Gort, T.Jeroen Jeroen Nicolaas Hiltermann, Hiroki Izumi, Dong-Wan Kim, Sang-We Kim, Luis G. Paz-Ares, Benjamin J. Solomon, Laurie Steinbusch, Els Wauters, Tatsuya Yoshida, Huifang Chen, Andrew Goldwin, Yu Jiang, Ikbel Achour, Moritz Wolfgang Drachsler, Byoung Chul Cho

Title

Safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of AZD2936, a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-experienced advanced/metastatic non-small-cell lung cancer (NSCLC): First report of ARTEMIDE-01.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	41	no. 16_suppl	June 01, 2023

URL

https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9050

Abstract Text

Background: PD-1 and TIGIT are implicated in cancer-related T cell immunosuppression. AZD2936 is a bispecific, humanized IgG1 (triple-mutated to minimize Fc effector function) targeting PD-1 and TIGIT. It has demonstrated encouraging activity compared to both anti-PD-1 and anti-PD-1/-TIGIT combinations in murine models. We report data from dose escalation (Part A) and an expansion cohort (Part B) of the first-in-human study ARTEMIDE-01 (NCT04995523). Methods: This open-label, multicenter study enrolled pts with advanced NSCLC who had prior CPI treatment and a PD-L1 tumor proportion score ≥1%. Part A evaluated doses of 70–1500 mg IV Q3W; Part B evaluated the recommended phase 2 dose (RP2D). Primary endpoints included safety, tolerability, dose-limiting toxicities (DLTs) and preliminary efficacy. Secondary endpoints included PK and PD, defined as percentage PD-1 and TIGIT receptor occupancy (RO). Results: As of Dec 5, 2022, 80 pts were enrolled (Part A, n=48; Part B, n=32). Pts were 62.5% male, median age 63.5 years; 72.5% had adenocarcinoma, 23.8% had squamous cell carcinoma; 96.3% had metastatic disease; and 22.5% had brain metastases. They had a median of 2 prior regimens. Median duration of therapy was 11 wks. AZD2936 was well tolerated with no DLTs. In total, 46.3% of pts had treatment-related adverse events (TRAEs), all grade 1–3; the most common were pruritus, rash and lipase increased (6.3% each). Serious TRAEs occurred in 3 pts (3.8%): immune system disorder, acute hepatitis and fatigue (n=1 each). AZD2936 systemic exposure increased in a near dose-proportional manner. Doses of ≥210 mg achieved ~90% PD-1 and TIGIT RO in peripheral T cells. The RP2D was determined to be 750 mg Q3W based on safety, preliminary efficacy, PK/PD and modeling analysis predicting intratumoral RO. Among 76 evaluable pts, 3 had a partial response and 30 had stable disease (Table). Time to response was 1.9–4.0 mos and duration of response was 2.1–6.4 mos. Conclusions: In this interim analysis, AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy including CPIs. Further exploration of AZD2936 in CPI-naïve NSCLC pts, including a randomized dose optimization cohort is ongoing. Clinical trial information: NCT04995523.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CD274 positive	lung non-small cell carcinoma	predicted - sensitive	AZD2936	Phase I	Actionable	In a Phase I trial (ARTEMIDE-01), AZD2936 treatment demonstrated acceptable safety and activity in patients with CD274 (PD-L1)-positive (TPS >/= 1%) advanced non-small cell lung cancer, with an overall response rate of 3.9% (3/76, 3 partial responses), stable disease in 39.5% (30/76), disease control rate (DCR) at 9 weeks of 43.4% (33/76), and a DCR at 27 weeks of 14.5% (11/76), with a duration of response of 2.1-6.4 mo (J Clin Oncol 41, 2023 (suppl 16; abstr 9050); NCT04995523).	detail...