MK-4166 / Merck (MSD) - LARVOL DELTA

Phase 1 study of MK-4166, an anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) antibody, as monotherapy or with pembrolizumab (pembro) in patients (pts) with advanced solid tumors. (ASCO 2019) - P1; "MK-4166 at a dose up to 900 mg as monotherapy and in combination with pembro was well tolerated, with dose-related evidence of target engagement. Responses were observed with MK-4166 900 mg plus pembro, particularly in pts with melanoma naive to ICIs. Clinical trial information: NCT02132754"

Clinical • IO Biomarker • Monotherapy • P1 data • PD(L)-1 Biomarker

Phase I Study of MK-4166, an Anti-Human Glucocorticoid-Induced Tumor Necrosis Factor Receptor Antibody, Alone or With Pembrolizumab in Advanced Solid Tumors. (PubMed, Clin Cancer Res) - P1 | "MK-4166 900 mg IV Q3W as monotherapy and with pembrolizumab was tolerable. Responses were observed with combination therapy, mostly in patients with ICI-naive melanoma."

IO biomarker • Journal • P1 data • Melanoma • Oncology • Solid Tumor

[VIRTUAL] GITR agonist sensitizes MC38/OVA tumor to CTLA4 treatment by attenuating Tregs in GITR HuGEMM (AACR-NCI-EORTC 2020) - "We then inoculated MC38-OVA syngeneic tumors into the GITR HuGEMM mice and treated the mice with 30 mpk of anti-human GITR (MK4166) and 5 mpk of anti-mouse CTLA-4 (9D9) 3 days post tumor engraftment (Day 4)... Our GITR HuGEMM provides ideal and powerful preclinical animal models to evaluate the efficacy of the human GITR antibodies or its combination with CTLA-4 or other immune modulators."

IO Biomarker • Oncology • CD8 • CTLA4 • FOXP3 • TNFRSF8

Biomarker-Driven Therapy Using Immune Activators With Nivolumab in Patients With First Recurrence of Glioblastoma (clinicaltrials.gov) - P1; N=3; Terminated; Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; N=30 ➔ 3; Trial completion date: Feb 2024 ➔ Jun 2020; Active, not recruiting ➔ Terminated; Trial primary completion date: Feb 2022 ➔ Nov 2019; Funding/material support withdrawn

Biomarker • Clinical • Combination therapy • Enrollment change • IO Biomarker • Trial completion date • Trial primary completion date • Trial termination • Brain Cancer • Glioblastoma • Melanoma • Oncology • Solid Tumor

Biomarker-Driven Therapy Using Immune Activators With Nivolumab in Patients With First Recurrence of Glioblastoma (clinicaltrials.gov) - P1; N=30; Active, not recruiting; Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Recruiting ➔ Active, not recruiting

Biomarker • Clinical • Combination therapy • Enrollment closed • IO Biomarker • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Melanoma • Oncology • Solid Tumor

Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001) (clinicaltrials.gov) - P1; N=113; Completed; Sponsor: Merck Sharp & Dohme Corp.; Active, not recruiting ➔ Completed

Clinical • Combination therapy • Trial completion

"MK-4166 at a dose up to 900 mg as monotherapy and in combination with pembrolizumab 200 mg every 3 weeks was well tolerated. #ASCO19" (@Cortellis)

Combination therapy • Monotherapy

Biomarker-Driven Therapy Using Immune Activators With Nivolumab in Patients With First Recurrence of Glioblastoma (clinicaltrials.gov) - P1; N=30; Recruiting; Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Not yet recruiting ➔ Recruiting

Biomarker • Clinical • Combination therapy • Enrollment open • IO Biomarker • PD(L)-1 Biomarker