dulanermin (AMG 951) / Amgen, Roche - LARVOL DELTA

Aminopeptidase N Inhibitors as Pointers for Overcoming Antitumor Treatment Resistance. (PubMed, Int J Mol Sci) - "Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin...In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme."

Journal • Oncology

The TRAIL in the Treatment of Human Cancer: An Update on Clinical Trials. (PubMed, Front Mol Biosci) - "We have also aimed to introduce all novel approaches of TRAIL utilization in cancer treatment and discussed the most promising drugs which are likely to enter clinical trials in humans. To date, different strategies were introduced in order to activate anti-tumor immune responses with the aim of achieving the highest efficacy and minimal toxicity.In this review, we discuss the most promising TRAIL-based clinical trials and their therapeutic strategies."

Clinical • Journal • Review • TNFA • TNFSF10

"Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist https://t.co/RJHYp6Px8S" (@VivekSubbiah)

Oncology • Sarcoma • Solid Tumor

"Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist @MCT_AACR @MCT_AACR https://t.co/RJHYp6Px8S" (@VivekSubbiah)

Oncology • Sarcoma • Solid Tumor

Phase Ib study of dulanermin combined with first-line FOLFOX plus bevacizumab (BV) in patients (Pts) with metastatic colorectal cancer (mCRC) (ASCO 2012) - Presentation time: Monday Jun 4, 8:00 AM to 12:00 PM; P1b, N=23; APO3583g; No DLTs were reported; Best responses included 13 PR (9 confirmed & 4 unconfirmed), 7 SD & 3 PD; Three pts discontinued study treatment due to SAEs

P1 data • Colorectal Cancer • Oncology

Dulanermin with rituximab in patients with relapsed indolent B-cell lymphoma: an open-label phase 1b/2 randomised study. (PubMed) - P1/2; "The addition of dulanermin to rituximab in patients with indolent B-cell non-Hodgkin lymphoma was tolerable but did not lead to increased objective responses. This combination is not being developed further in non-Hodgkin lymphoma."

Journal • Biosimilar • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Engineering and preclinical activity of MM-201, a best-in-class TRAIL receptor agonist (AACR 2019) - "...First generation TRAIL agonists included a recombinant version of human TRAIL (dulanermin), as well as multiple DR4 and DR5 agonist antibodies...In the same model, treatment with 10 mg/kg docetaxel resulted in 73% growth inhibition; however, in combination with MM-201a, the same dose resulted in a 100% complete response rate. Similar results were observed in the SK-UT1 uterine sarcoma xenograft. Based on this evidence, we believe that MM-201b is best in class and, when combined with an appropriate patient selection strategy, has significant potential for the treatment of sarcomas and colorectal cancer in patients."

Preclinical