rilotumumab (AMG 102)

P1/2, N=213, Terminated, NantCell, Inc. | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Subjects discontinued study

P1/2, N=177, Completed, NantBioScience, Inc. | Phase classification: P1b/2 --> P1/2

Although resistant cells were significantly more malignant, they retained sensitivity to Met kinase inhibition and acquired sensitivity to inhibition of ER stress signaling and cholesterol biosynthesis. Defining this mechanism reveals details of a rapidly acquired yet highly-orchestrated multisystem route of resistance to a selective molecularly-targeted agent and suggests strategies for early detection and effective intervention.

P=N/A, N=1864, Completed, Southwest Oncology Group | Active, not recruiting --> Completed

Randomised controlled trials (RCTs) were undertaken assessing whether the addition of anti-HGF/MET agent (rilotumumab or onartuzumab) to chemotherapy improves survival outcomes of advanced GC, but conflict conclusions were reached...It is anticipated that the dissemination of results will take place at conferences and through publication in a peer-review journal, any adjustments from the protocol will be clearly documented and explained in its final report. CRD42020177404.

In the MEGA-ACCORD20-PRODIGE17 trial, GC patients received an anti-HGF antibody treatment (rilotumumab), which had been described to have an anti-angiogenic activity by decreasing proliferation of endothelial cells and tube formation...Thus, we identified that HGF indirectly triggers Treg accumulation via c-Met-expressing monocytes in the peripheral blood of GC patients. Our study provides arguments for potential alternative use of HGF/c-Met targeted therapies based on their immunomodulatory properties which could lead to the development of new therapeutic associations in cancer patients, for example with immune checkpoint inhibitors.

Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors. Recently, capmatinib was approved for treatment of metastatic lung cancer with MET exon 14 skipping...Preclinical and clinical studies on the combination of HGF/MET-targeted agents with conventional chemotherapeutics or molecularly targeted treatments (EGFR, VEGFR, HER2, RAF/MEK, and PI3K/Akt targeting agents) and also the value of biomarkers are examined. Our deeper understanding of molecular mechanisms underlying successful pharmacological combinations is crucial to find the best personalized treatment regimens for cancer patients.

P2, N=162, Completed, UNICANCER | Active, not recruiting --> Completed

P=N/A, N=1864, Active, not recruiting, Southwest Oncology Group | Phase classification: P2/3 --> P=N/A | N=10000 --> 1864

P2/3;Lung-MAP (S1400) met its goal to quickly address biomarker-driven therapy questions in squamous non-small-cell lung cancer. In early 2019, a new screening protocol was implemented expanding to all histological types of non-small-cell lung cancer and to add focus on immunotherapy combinations for anti-PD-1 and anti-PD-L1 therapy-relapsed disease. With these changes, Lung-MAP continues to meet its goal to focus on unmet needs in the treatment of advanced lung cancers.

PSCs can activate the c-Met/PI3K/Akt pathway in PCCs via paracrine HGF, induce EMT of PCCs and inhibit cancer cell apoptosis, thus enhance chemoresistance to Gem in PCCs.

We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients.