- |||||||||| conatumumab (AMG 655) / Amgen
Journal: The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL. (Pubmed Central) - Oct 4, 2024 Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.
- |||||||||| ganitumab (AMG 479) / Takeda, ImmunityBio
Phase classification, Combination therapy, Metastases: QUILT-3.026: AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors (clinicaltrials.gov) - Aug 20, 2024 P1/2, N=89, Terminated, These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD. Phase classification: P1b/2 --> P1/2
- |||||||||| conatumumab (AMG 655) / Amgen
Journal: TRAIL-Based Therapies Efficacy in Pediatric Bone Tumors Models Is Modulated by TRAIL Non-Apoptotic Pathway Activation via RIPK1 Recruitment. (Pubmed Central) - Nov 27, 2022 The DR5 agonist antibody AMG655 (Conatumumab) was selected as an example of TRAIL-based therapy...We proposed two independent strategies to overcome this issue: (1) a proof-of-concept targeting of RIPK1 by shRNA approach and (2) the use of a novel highly-potent TRAIL-receptor agonist; both shifting the balance in favor of apoptosis. These observations are paving the way to resurrect TRAIL-based therapies in pediatric bone tumors to help predict the response to treatment, and propose a relevant adjuvant strategy for future therapeutic development.
- |||||||||| irinotecan / Generic mfg.
Preclinical, Journal: DR5-targeted, chemotherapeutic drug-loaded nanoparticles induce apoptosis and tumor regression in pancreatic cancer in vivo models. (Pubmed Central) - Jun 22, 2021 To take advantage of elevated expression of this pathway, we designed drug-loaded NPs with a surface-conjugated αDR5 antibody (AMG 655)...Moreover, the DNA topoisomerase-1 inhibitor camptothecin (CPT) down-regulated FLIP in pancreatic cancer models and enhanced apoptosis induced by αDR5-NPs...Importantly, CPT-loaded αDR5-NPs markedly reduced tumor growth rates in vivo in established pancreatic tumor models, inducing regressions in one model. These proof-of-concept studies indicate that αDR5-NPs loaded with agents that downregulate or inhibit FLIP are promising candidate agents for the treatment of pancreatic cancer.
- |||||||||| conatumumab (AMG 655) / Amgen
Journal: The serum protein transthyretin as a platform for dimerization and tetramerization of antibodies and Fab fragments to enable target clustering. (Pubmed Central) - Jan 14, 2021 These proof-of-concept studies indicate that αDR5-NPs loaded with agents that downregulate or inhibit FLIP are promising candidate agents for the treatment of pancreatic cancer. Transthyretin (TTR) is an abundant homo-tetrameric serum protein and was selected here for engineering higher-valency molecules because its compact size, simple structure, and natural propensity to tetramerize. To demonstrate this utility, we fused TTR to the C terminus of conatumumab, an antibody that targets tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), as heavy chains to form antibody dimers and Fab heavy chains to form Fab tetramers. Moreover, we used constant heavy domain 3 (CH3) heterodimerization substitutions to create TTR-mediated conatumumab tetramers. The conatumumab-TTR fusions displayed substantially enhanced potency in cell-based assays as well as in murine tumor xenograft models. We conclude that antibody-TTR fusions may provide a powerful platform for multimerizing antibody and Fab fragments to enhance the capabilities of human therapeutics that benefit from target clustering and higher-order antigen-binding valency.
- |||||||||| conatumumab (AMG 655) / Amgen
Trial completion date, Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Dec 19, 2019 P2, N=12, Active, not recruiting, Active, not recruiting --> Completed Trial completion date: Nov 2019 --> Mar 2020 | Trial primary completion date: Sep 2019 --> Mar 2020
- |||||||||| conatumumab (AMG 655) / Amgen
Trial completion date, Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Nov 6, 2018 P2, N=12, Active, not recruiting, Trial completion date: Nov 2019 --> Mar 2020 | Trial primary completion date: Sep 2019 --> Mar 2020 Trial completion date: Jan 2019 --> Nov 2019 | Trial primary completion date: Jan 2019 --> Sep 2019
- |||||||||| conatumumab (AMG 655) / Amgen
Trial completion date, Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Jul 18, 2018 P2, N=12, Active, not recruiting, Trial completion date: Jan 2019 --> Nov 2019 | Trial primary completion date: Jan 2019 --> Sep 2019 Trial completion date: Jul 2018 --> Jan 2019 | Trial primary completion date: Jul 2018 --> Jan 2019
- |||||||||| conatumumab (AMG 655) / Amgen
Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Nov 30, 2017 P2, N=12, Active, not recruiting, Further research is needed to achieve effective therapy for patients with EGFR mutation L858R or nonsquamous histology. Trial primary completion date: Jan 2018 --> Jul 2018
- |||||||||| conatumumab (AMG 655) / Amgen
Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Apr 20, 2015 P2, N=12, Active, not recruiting, Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2015 --> Aug 2015 Trial primary completion date: Apr 2015 --> Dec 2015
- |||||||||| conatumumab (AMG 655) / Amgen
Enrollment closed, Trial primary completion date: Open Label Extension Study of Conatumumab and Ganitumab (AMG 479) (clinicaltrials.gov) - Feb 20, 2015 P2, N=12, Active, not recruiting, Trial primary completion date: Apr 2015 --> Dec 2015 Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2014 --> Apr 2015
- |||||||||| ganitumab (AMG 479) / Takeda, ImmunityBio
Trial termination, Combination therapy, Metastases: QUILT-3.026: AMG 655 in Combination With AMG 479 in Advanced, Refractory Solid Tumors (clinicaltrials.gov) - Sep 30, 2012 P1/2, N=89, Terminated, Active, not recruiting --> Completed Active, not recruiting --> Terminated; Sponsor decision - subjects rolled over to protocol 20101116
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