DRAGON TRIAL: DURABLE REMISSION RATE WITH THE LATENT TGFb1 INHIBITOR LINAVONKIBART (SRK-181) AND PEMBROLIZUMAB IN PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR RESISTANT ADVANCED CANCERS
Recommended Citation
Yap TA, Sweis R, Vaishampayan UN, Kilari D, Tarhini AA, Gainor JF, Barve M, Sonpavde GP, Park D, Babu S, McKay R, Hwang C, Sher A, Nangia C, Kim M, Choi J, Ju Y, Liu L, Henry S, DeWall S, Gan L. DRAGON TRIAL: DURABLE REMISSION RATE WITH THE LATENT TGFb1 INHIBITOR LINAVONKIBART (SRK-181) AND PEMBROLIZUMAB IN PATIENTS WITH IMMUNE CHECKPOINT INHIBITOR RESISTANT ADVANCED CANCERS. J Immunother Cancer 2024; 12:A917.
Document Type
Conference Proceeding
Publication Date
11-1-2024
Publication Title
J Immunother Cancer
Keywords
biological marker, CD8 antigen, immune checkpoint inhibitor, immunoglobulin G4, linavonkibart, pembrolizumab, transforming growth factor beta1, adult, advanced cancer, aged, antineoplastic activity, cancer inhibition, CD8+ T lymphocyte, cell infiltration, clinical outcome, conference abstract, diagnosis, diarrhea, erythroderma, fatigue, female, flow cytometry, head and neck squamous cell carcinoma, human, human tissue, immunohistochemistry, immunosuppressive treatment, major clinical study, melanoma, non small cell lung cancer, pemphigoid, pruritus, rash, regulatory T lymphocyte, remission, response evaluation criteria in solid tumors, transitional cell carcinoma, tumor escape, tumor microenvironment
Abstract
Background Transforming growth factor-beta 1 isoform (TGFb1) drives tumor immune escape by promoting an immunosuppressive pro-tumor microenvironment. Linavonkibart is a first-in-class fully human IgG4 context-independent anti-latent TGFb1 monoclonal antibody. Methods Linavonkibart+pembrolizumab showed antitumor activity with no dose-limiting toxicity during dose escalation. In expansion cohorts, linavonkibart (1500mg q3w)+Pembroliizumab were administered in melanoma (MEL), urothelial carcinoma (UC), and non-small cell lung cancer (NSCLC) patients, who were non-responders to prior anti-PD1; and in clear cell renal cell carcinoma (ccRCC) and head and neck squamous cell carcinoma (HNSCC) patients, with disease progression on the most recent prior anti-PD1. Biomarker analyses include immunohistochemistry and flow cytometry. Results As of 11 Jun 2024, 78 patients (28.2% females, median age 65 years) were enrolled. Patients had received a median of 3 prior lines of therapies (range 1-9). All patients had a best response of SD or PD on prior anti-PD1 (except 1 HNSCC patient, who had PR). All patients had progressed on their most recent anti-PD1 (except 2 MEL patients). Treatment- related AEs (TRAE, ≥10%) of any grade were rash (33.3%), pruritus (26.9%), fatigue (21.8%) and diarrhea (15.4%). Rash (12.8%) was the only grade 3 TRAE (≥5%); only one grade 4 TRAE (dermatitis exfoliative generalized) occurred. There was no grade 5 TRAE. Treatment-related SAE (≥2% [2 pt]) was pemphigoid (2.6%). Efficacy results are presented in the table below. Tumor assessments were based on RECIST 1.1 criteria by PI. PFS rate (95% CI) for ccRCC patients at 6 months and 9 months were 44% (25.6, 61) and 28.6% (12.1, 47.5), respectively. (table 1). In ccRCC patients, baseline CD8+ T-cell infiltration status and baseline Treg levels correlated with positive clinical outcome: ORR increased to 33% (4/12) and 57.1% (4/7) for CD8+ infiltrated patients and elevated Treg patients, respectively. Across all cohorts, treatment with linavonkibart+Pemmbrolizumab shifted the microenvironment to more proinflammatory in responding patients. Conclusions Linavonkibart+Pembrolizumab treatment demonstrated promising efficacy in anti-PD1 resistant patients across multiple tumor types with a manageable safety profile. Baseline biomarker data from ccRCC patients showed clinical outcomes correlated with CD8+ infiltration and elevated Treg Levels, suggesting a potential patient selection strategy. These data support further investigation of linavonkibart. .
PubMed ID
Not assigned.
Volume
12
First Page
A917
