pogalizumab (MOXR0916) / Roche - LARVOL DELTA

SHR-1806, a robust OX40 agonist to promote T cell-mediated antitumor immunity. (PubMed, Cancer Biol Ther) - "In human OX40 knock-in mice bearing MC38 tumor, SHR-1806 shows a trend toward a higher potency than the reference anti-OX40 antibody produced in-house, GPX4, an analog of pogalizumab, the most advanced drug candidate developed by Roche. Evaluation of SHR-1806 in rhesus monkeys indicates a favorable safety profile and typical pharmacokinetic characteristics. Thus, SHR-1806 emerges as a robust OX40 agonist with promising therapeutic potential."

Journal • Oncology • CD8 • GPX4 • TNFSF4

Structural Basis of a Novel Agonistic Anti-OX40 Antibody. (PubMed, Biomolecules) - "Our crystallography structural studies showed that DF004 binds to the CRD2 region of OX40 while RG7888, an OX40 agonist antibody developed by Roche, binds to CRD3 of OX40 to the diametrically opposite position of DF004...As their agonistic activities critically depend on clustering or cross-linking, our structural modeling indicates that the agonistic activity requires the optimal positioning of three Fc receptor/antibody/OX40 complexes on the cell membrane to facilitate the formation of one intracellular hexameric TRAF complex for downstream signal transduction, which is relatively inefficient. This may explain the lack of sufficient potency of these OX40 antibodies in a therapeutic setting and sheds light on the development of cross-linking-independent agonistic antibodies."

Journal • Immune Modulation • Inflammation • Oncology • CD4

First-In-Human Phase I Study of the OX40 Agonist MOXR0916 in Patients with Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "Although objective responses were rarely observed with MOXR0916 monotherapy, the favorable safety profile and evidence of tumor immune activation in a subset of patients support further investigation in combination with complementary agents such as PD/PD-L1 antagonists."

Journal • P1 data • Breast Cancer • Fatigue • Genito-urinary Cancer • Immune Modulation • Inflammation • Lung Cancer • Melanoma • Musculoskeletal Pain • Non Small Cell Lung Cancer • Oncology • Pain • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • PD-L1

Novel set of OX40 targeted antibodies and VHHs include agonists and antagonists for future development (AACR 2022) - "Agonist activity was equal to MOXR0916 in NF- κB reporter-Jurkat assay, dependent on coupling by proteinA/cell-bound CD32b, non-competing with OX40L, and epitope mapped to domain 2+3.We identified dozens of binders from our synthetic single domain VH library...Another 5 VHHs were also obtained with significant antagonistic activity without coupling by proteinA/cell-bound CD32b. The 4 agonistic VHHs were confirmed with binding to domain 1+2, competitive to OX40L’s binding.These VHHs constructs represent a promising set of novel biologics to modulate OX40—as agonists or antagonists—and serve as the basis for development of potential new therapies in the clinic."

Brain Cancer • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • FOXP3 • HAVCR2 • LAG3 • TIGIT

[VIRTUAL] A differentiated anti-OX40 agonist BGB-A445 does not block OX40-OX40L interaction and reveals remarkable anti-tumor efficacy in preclinical models (SITC 2020) - "In contrast, MOXR0916, an anti-OX40 agonistic antibody developed by Genentech, completely blocked OX40 binding to OX40L. Conclusions In conclusion, differentiated from current clinical stage anti-OX40 antibodies, BGB-A445 is an agonistic antibody that does not block the OX40-OX40L interaction. Both in vitro and in vivo results demonstrated that BGB-A445 has remarkable immune stimulating effect and anti-tumor efficacy either as a single agent or in combination with anti-PD-1 therapy, thus warranting further clinical investigation."

Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • IL2 • TNFA

[VIRTUAL] A differentiated anti-OX40 agonist BGB-A445 does not block OX40-OX40L interaction and reveals remarkable anti-tumor efficacy in preclinical models (SITC 2020) - "In contrast, MOXR0916, an anti-OX40 agonistic antibody developed by Genentech, completely blocked OX40 binding to OX40L. Conclusions In conclusion, differentiated from current clinical stage anti-OX40 antibodies, BGB-A445 is an agonistic antibody that does not block the OX40-OX40L interaction. Both in vitro and in vivo results demonstrated that BGB-A445 has remarkable immune stimulating effect and anti-tumor efficacy either as a single agent or in combination with anti-PD-1 therapy, thus warranting further clinical investigation."

Preclinical • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • IL2 • TNFA

OX40 agonists for cancer treatment: a patent review. (PubMed, Expert Opin Ther Pat) - "United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists."

Journal • Immune Modulation • Inflammation • Oncology

Roche: Q1 FY 2016 Results (Roche) - Anticipated data from P1 trial of atezolizumab + RG7888 (anti-OX40 MAb) (NCT02410512) for solid tumors at ASCO (June 3-7, 2016); Anticipated data from P1 trial of atezolizumab + Cotellic (NCT01988896) for CRC at ASCO; Anticipated OS update from P2 POPLAR trial (NCT01903993) for 2/3L NSCLC at ASCO; Anticipated updates from first-line and second-line cohorts of P2 IMvigor210 trial (NCT02108652) for bladder cancer at ASCO; Anticipated update from P1 trial (NCT01633970) in combination with Abraxane in TNBC at ASCO

Anticipated P1 data • Anticipated P2 data • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Non Small Cell Lung Cancer • Oncology • Triple Negative Breast Cancer

A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors (ASCO 2016) - P1b, N=44; NCT02410512; Sponsor: Genentech; "The PK of each mAb was consistent with its established single agent profile. Objective responses were observed; clinical and biomarker data will be updated. The regimen selected for dose expansion is MOXR0916 300 mg + atezolizumab 1200 mg q3w."

P1 data • Oncology

RG7888: Anticipated data from P1 trial (NCT02219724) in solid tumors in 2017… (Roche) - FY 2016 Results: Anticipated data from P1 trial (NCT02219724) in solid tumors in 2017; Anticipated data from P1 trial (NCT02410512) of RG7888 (aOX40) + Tecentriq in solid tumors in 2017

Anticipated P1 data • Oncology

Development and characterization of a novel anti-OX40 antibody for potent immune activation. (PubMed, Cancer Immunol Immunother) - "Recently, several anti-OX40 agonistic monoclonal antibodies, pogalizumab as the most advanced, have entered early phase clinical trials. Preclinical studies of IBI101 in non-human primates demonstrate typical pharmacokinetic characteristics of an IgG antibody and no drug-related toxicity. Collectively, IBI101 has desirable preclinical attributes which support its clinical development for cancer treatment."

Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Solid Tumor

Product discontinued (Roche Press Release) - Oncology

Discontinued • Oncology

A first-in-human phase I dose escalation study of the OX40 agonist MOXR0916 in patients with refractory solid tumors (AACR 2016) - P1, N=34; "In a heterogeneous, refractory population, MOXR0916 was well-tolerated at all doses evaluated. The recommended dose and schedule based on PK and OX40 receptor saturation is 300 mg q3w."

P1 data • Oncology

A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=174; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed; Trial completion date: Jan 2020 ➔ Aug 2019

Clinical • Trial completion • Trial completion date

A Study to Assess the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab (Also Known as MPDL3280A or Anti-PD-L1) in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=610; Completed; Sponsor: Genentech, Inc.; Active, not recruiting ➔ Completed

Clinical • PD(L)-1 Biomarker • Trial completion

A Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy (clinicaltrials.gov) - P2; N=5; Terminated; Sponsor: Genentech, Inc.; Completed ➔ Terminated; The study was prematurely terminated due to slow patient accrual and discontinuation of clinical development of MOXR0916 due to Sponsor's strategic priorities.

Clinical • Combination therapy • Trial termination

A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1; N=174; Active, not recruiting; Sponsor: Genentech, Inc.; Trial completion date: Mar 2019 ➔ Dec 2019

Clinical • Trial completion date