Tomivosertib added on to continued checkpoint inhibitor therapy in patients with insufficient response to single-agent treatment
Despite the broad activity of checkpoint inhibitors across tumor types, primary or secondary resistance after initial response represents a major challenge.
Tomivosertib, a potent and highly selective inhibitor of the immunosuppressive kinases MNK-1 and 2, blocks expression of checkpoint proteins PD-1, PD-L1, and LAG-3 as well as immunosuppressive cytokines IL-6 and IL-8.
In preclinical models, Tomivosertib was shown to trigger an anti-tumor immune response and enhance the activity of checkpoint inhibitors in a T-cell dependent manner.
In prior clinical studies, Tomivosertib had an acceptable safety profile as a single agent and in combination with anti-PD-L1 agent Avelumab.
Patients experiencing insufficient response ( progression or stable disease for 12 weeks or more ) to any FDA-approved checkpoint inhibitor in any approved indication were eligible.
Tomivosertib at 200 mg oral ( PO ) BID ( twice a day ) was added to the existing checkpoint inhibitor until disease progression or unacceptable toxicity was noted.
39 patients ( 23 male, 16 female ) were enrolled across seven cancer types. Median age was 68 ( range 42-85 ). Median prior therapies were 2 ( range 1-6 ).
The most common cancers were lung ( n=17 ), urothelial ( n=6 ), renal ( n=5 ) and head and neck ( n=5 ).
36 patients continued on anti PD-1 antibody ( Pembrolizumab and Nivolumab, 18 each ) and 3 on anti PD-L-1 antibody ( Durvalumab 2, Atezolizumab 1 ).
The most common grade 3/4 treatment related adverse events occurring in more than 1 patient were alanine aminotransferase increase ( 2 ), blood creatine phosphokinase increase ( 2 ) and maculo-papular rash ( 2 ).
7 patients discontinued treatment ( 18% ) due to adverse events attributable to either drug.
Three partial responses ( PR ) per RECIST 1.1 were observed in patients with previous progression on checkpoint inhibitor therapy, one each in NSCLC ( 1/17 ), gastric ( 1/1 ) and renal cancer ( 1/5 ).
7 patients (41%) with NSCLC were progression free for 24 weeks or more. All NSCLC patients entered the study with progression by RECIST 1.1 on single agent checkpoint inhibitor prior to adding Tomivosertib.
In conclusion, the addition of Tomivosertib to existing checkpoint therapy was well tolerated and manifested clinical activity including objective responses in patients with progression on existing checkpoint inhibitor.
A progression-free survival rate at 24 weeks of 41% was noted in NSCLC patients. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020
Sotorasib has shown rapid, deep and durable responses in previously treated patients with advanced non-small cell lung cancer with KRAS G12C mutation
Results from the phase 2 cohort of the CodeBreaK 100 clinical study evaluating investigational Sotorasib ( AMG 510 ) in...
The FDA ( Food and Drug Administration ) has approved Enhertu ( fam-Trastuzumab Deruxtecan-nxki; fam-Trastuzumab Deruxtecan ) for adult patients...
RNAi therapeutics for treatment of hypertension: sustained reductions in serum angiotensinogen at 12 weeks and reduced blood pressure with single dose of ALN-AGT
Interim results from the ongoing phase 1 study of ALN-AGT, a subcutaneous investigational RNAi therapeutic targeting liver-expressed angiotensinogen ( AGT...
Ponvory for the treatment of adults with relapsing forms of multiple sclerosis with active disease - Approved in European Union
The European Commission ( EC ) has approved Ponvory ( Ponesimod ) for the treatment of adult patients with relapsing...
The Food and Drug Administration ( FDA ) has approved the first oral gonadotropin-releasing hormone ( GnRH ) receptor antagonist,...
The objective of a study was to delineate the clinical characteristics of patients with coronavirus disease 2019 ( Covid-19 )...
BRIGHTSTAR trial: local consolidative therapy with Brigatinib in TKI-naïve ALK-rearranged advanced non-small-cell lung cancer
Approximately, 95% of patients who have an initial response to ALK tyrosine kinase inhibitors ( ALK-TKIs ) exhibit an incomplete...
FDA has approved Retevmo, the first therapy for patients with lung and thyroid cancers with a mutation or fusion in gene RET
The U.S. Food and Drug Administration ( FDA ) has approved Retevmo ( Selpercatinib ) capsules to treat three...
RET fusions are oncogenic drivers in 1 to 2% of non–small-cell lung cancers ( NSCLCs ). In patients with RET...