Startseite Kongressberichte & Archiv 2021 ASCO Annual Meeting Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
A first-in-human phase 1 study of a novel PARP7 inhibitor RBN-2397 in patients with advanced solid tumors.
Gerald Steven Falchook, Manish R. Patel, Timothy A. Yap, et al.
The study authors show that RBN-2397 is well tolerated and demonstrates dose-dependent increases in plasma exposures. There is evidence of target inhibition and preliminary signs of clinical activity. Clinical trial information: NCT04053673
First-in-human biomarker-driven phase I trial of the potent and selective glutaminase-1 (GLS1) inhibitor IACS-6274 (IPN60090) in patients (pts) with molecularly selected advanced solid tumors.
Timothy A. Yap, Ecaterina Elena Dumbrava, Jordi Rodon Ahnert, et al.
The study authors observed that IACS-6274 was well tolerated at biologically active doses with good human PK, significant PD target modulation, and preliminary antitumor activity. Clinical trial information: NCT03894540
Peter Meade Anderson, Janette Gortz;
ONC201 is an imipridone with specificity for the dopamine-like DRD2 receptor and the mitochondrial protease ClpP. According to the study authors, the drug is well tolerated at 625mg weekly in adults with advanced neuroendocrine tumors. ONC201 is associated with clinical benefits including tumor response, particularly in paraganglioma patients. Clinical trial information: NCT03034200
Efficacy and safety of zenocutuzumab in advanced pancreas cancer and other solid tumors harboring NRG1 fusions.
Alison M. Schram, Eileen Mary O'Reilly, Grainne M. O'Kane, et al.
Zenocutuzumab is a bispecific antibody targeting NRG1 fusion signaling in NRG1 fusion-positive (NRG1+) cancers. According to the study authors the drug induces rapid and major radiologic tumor regression and biomarker responses in heavily-pretreated metastatic KRAS wild-type NRG1+ pancreas cancer. There was minimal toxicity observed. The authors conclude that zenocutuzumab is a promising novel targeted therapeutic option for patients with NRG1+ cancers. Clinical trial information: NCT02912949
MyPathway HER2 basket study: Pertuzumab (P) + trastuzumab (H) treatment of a large, tissue-agnostic cohort of patients with HER2-positive advanced solid tumors.
Funda Meric-Bernstam, John Hainsworth, Ron Bose, et al.
The study authors conclude that the combination of Pertuzumab (P) + trastuzumab (H) was active in a wide variety of KRAS wild-type HER2-amplified/overexpressed tumor types. However, the combination had limited activity in KRAS-mutated tumors. Clinical trial information: NCT02091141
Initial results from a dose finding study of TNO155, a SHP2 inhibitor, in adults with advanced solid tumors.
Irene Brana, Geoffrey Shapiro, Melissa Lynne Johnson, et al.
TNO155 is a selective, allosteric, oral inhibitor of SHP2. The study authors found favorable pharmacokinetic properties and promising early safety and tolerability data with this drug at doses with evidence of target inhibition. The optimal dose using several schedules is still under evaluation. See ongoing studies with TNO155 in combination with other agents: nazartinib (mutant-selective EGFR inhibitor[i]), adagrasib (KRAS G12Ci), spartalizumab (anti-PD-1 antibody), ribociclib (CDK4/6i), and dabrafenib (BRAFi) with LTT462 (ERKi) (NCT03114319, NCT04330664, NCT04000529, NCT04294160). Clinical trial information: NCT03114319
First-in-human phase I/II study of CYT-0851, a first-in-class inhibitor of RAD51-mediated homologous recombination in patients with advanced solid and hematologic cancers.
Ryan C Lynch, Johanna C. Bendell, Ranjana H. Advani, et al.
CYT-0851 is a first-in-class inhibitor of RAD51-mediated Hematologic Cancers. The study authors conclude that the drug is well-tolerated, with linear PK, target-directed PD effects, and promising antitumor activity across different tumor types. This is the first DNA-damage repair (DDR) therapeutic with demonstrated clinical activity in both hematologic malignancies and solid tumors. Clinical trial information: NCT03997968
A phase Ib trial of belvarafenib in combination with cobimetinib in patients with advanced solid tumors: Interim results of dose-escalation and patients with NRAS-mutant melanoma of dose-expansion.
Sang Joon Shin, Jeeyun Lee, Tae Min Kim, et al.
The study authors conclude that Belvarafenib - a potent, selective RAF dimer (type II) inhibitor - in combination with cobimetinib showed acceptable tolerability and encouraging efficacy in NRASm melanoma, and in those with prior immune checkpoint inhibitor treatment. Clinical trial information: NCT03284502
BOS172738, a highly potent and selective RET inhibitor, for the treatment of RET-altered tumors including RET-fusion+ NSCLC and RET-mutant MTC: Phase 1 study results.
Patrick Schoffski, Byoung Chul Cho, Antoine Italiano, et al.
The study authors conclude that BOS172738 is a highly potent and selective RET inhibitor with a differentiated safety profile. They observed clinical activity against RET-altered tumors. This includes patients with brain metastases. There is continuing evaluation in patients with NSCLC, MTC, and in patients previously treated with other selective RET inhibitors. Clinical trial information: NCT03780517