Abstract 2664
Background
MBG453 and spartalizumab are humanized IgG4 mAbs that block binding of TIM-3 to PtdSer and PD-1 to PD-L1/2, respectively. In Ph I dose escalation, MBG453 + spartalizumab showed preliminary antitumor activity in advanced solid tumors. Here we report Ph II MBG453 + spartalizumab dose expansion in pts with NSCLC and melanoma (NCT02608268).
Methods
Pts with melanoma or NSCLC who had progressive disease (PD) on/after anti–PD-1/L1 therapy received MBG453 (800 mg, Q4W) + spartalizumab (400 mg, Q4W) until unacceptable toxicity, PD, or investigator/pt decision. On prior anti–PD-1/L1 therapy clinical benefit (CB) was defined as durable (DCB) if pts had a complete or partial response, or stable disease (SD) for ≥6 months, or non-durable (NDCB) if pts had SD for <6 months or PD.
Results
As of Feb 15, 2019, 33 pts received MBG453 + spartalizumab (melanoma: n=16; NSCLC: n=17); 5 (15.2%) pts were ongoing (melanoma: n=3 [18.8%]; NSCLC: n=2 [11.8%]); 28 (84.8%) pts discontinued, mainly due to PD (60.6%) and death due to underlying disease (12.1%). Anti–PD-1/L1 was the last therapy before enrollment in 21 (63.6%) pts (melanoma: n=10 [62.5%]; NSCLC: n=11 [64.7%]). On prior anti–PD-1/L1 therapy, 6 (37.5%) melanoma and 7 (41.2%) NSCLC pts had DCB and 10 (62.5%) melanoma and 9 (52.9%) NSCLC pts had NDCB; CB was unknown (UNK) in 1 NSCLC pt. On MBG453 + spartalizumab, 3/16 (18.8%) melanoma pts (prior anti-PD-1/L1: DCB n=2; NDCB n=1) and 7/17 (41.2%) NSCLC pts (prior anti-PD-1/L1: DCB n=3; NDCB n=3; UNK n=1) had SD per RECIST 1.1. Baseline tumor PD-L1 appears higher in pts with SD vs PD. Data suggest a trend of inverse association between tumor reduction and CD163 tumor expression. Common treatment-related adverse events (TRAEs) were fatigue, nausea, and pruritus (n=3 each [9.1%]); 0 melanoma and 2 (11.8%) NSCLC pts (pruritus, amylase, lipase, and increased ALT) had Grade 3/4 TRAEs.
Conclusions
MBG453 (800 mg, Q4W) + spartalizumab (400 mg, Q4W) was well tolerated but with limited efficacy in pts with melanoma and NSCLC who had PD on/after prior anti–PD-1/L1 therapy. Further evaluation of MBG453 in other indications/combinations is needed to assess the clinical relevance of TIM-3 inhibition.
Clinical trial identification
Editorial acknowledgement
Editorial assistance was provided by Jenny Winstanley, PhD, of Articulate Science Ltd.
Resources from the same session
2036 - Salivary metabolomics for colorectal cancer detection
Presenter: Hiroshi Kuwabara
Session: Poster Display session 3
Resources:
Abstract
1868 - Evaluation and diagnostic potential of plasma biomarkers in bladder cancer
Presenter: Veronika Voronova
Session: Poster Display session 3
Resources:
Abstract
3655 - Liquid biopsy assays using combined circulating tumor cells and circulating tumor DNA in the same patients for the diagnosis of primary lung cancer
Presenter: Yongjoon Suh
Session: Poster Display session 3
Resources:
Abstract
3685 - Peripheral Cytotoxic T Cell Correlates with Tumor Mutational Burden and is Predictive for Progression Free Survival in Advanced Breast Cancer
Presenter: Xiao-ran Liu
Session: Poster Display session 3
Resources:
Abstract
1050 - Splenic Metabolic Activity as Biomarker in Cervical Cancer
Presenter: Emiel De Jaeghere
Session: Poster Display session 3
Resources:
Abstract
1413 - Identification of distinct subtypes revealing prognostic and therapeutic relevance in diffuse type gastric cancer
Presenter: Seon-Kyu Kim
Session: Poster Display session 3
Resources:
Abstract
2140 - Recurrence risk evaluation in stage IB/IIA gastric cancer with TP53 codon 72 polymorphisms
Presenter: Satoshi Nishizuka
Session: Poster Display session 3
Resources:
Abstract
1573 - Identification and validation of a prognostic 4 genes signature for hepatocellular carcinoma: integrated ceRNA network analysis
Presenter: Yongcong Yan
Session: Poster Display session 3
Resources:
Abstract
1196 - Plasma KIM-1 is associated with clinical outcomes after resection for localized renal cell carcinoma: A trial of the ECOG-ACRIN Research Group (E2805)
Presenter: Wenxin Xu
Session: Poster Display session 3
Resources:
Abstract
2657 - Prognostic immunoprofiling of muscle invasive bladder cancer (MIBC) patients in a multicentre setting
Presenter: Katharina Nekolla
Session: Poster Display session 3
Resources:
Abstract