Reference Detail

Ref Type

Abstract

PMID

Authors

Byoung Chul Cho, Ki Hyeong Lee, Ji-Youn Han, Byoung Yong Shim, Hye Ryun Kim, Kyoung-Ho Pyo, Jae-Hwan Kim, Chung-Feng Xin, Jin Kyung Lee, Jiyeon Ryu, Bitna Oh, Sunjin Hwang, Ki Baik Hahm and Seong-Jin Kim

Title

Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal for ImmunoTherapy of Cancer	Volume 8,	Suppl 3	2020

URL

https://jitc.bmj.com/content/8/Suppl_3/A222.1

Abstract Text

Abstract Background Targeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy. Methods Patients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1). Results By August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented. Conclusions The combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.

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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	Durvalumab + Vactosertib	Phase Ib/II	Actionable	In a Phase Ia/II trial, combination treatment with Vactosertib (TEW 7197) and Imfinzi (durvalumab) demonstrated safety and antitumor activity in CD274 (PD-L1)-positive non-small cell lung cancer patients, and led to an objective response rate of 30.8% and 40.0% in patients with CD274 (PD-L1) expression >= 1% and >=25% respectively (Journal for ImmunoTherapy of Cancer 2020;8; NCT03732274).	detail...