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
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract