A5049294543- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Protein Tyrosine Phosphatases
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Cancer-related gene regulation
- Biochemical and Molecular Research
- Lung Cancer Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Cancer Research and Treatments
- Radiopharmaceutical Chemistry and Applications
- Neuroendocrine Tumor Research Advances
- ATP Synthase and ATPases Research
- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
Tennessee Oncology
2016-2025
Sarah Cannon
2016-2025
Roswell Park Comprehensive Cancer Center
2025
Cancer Research Institute
2025
Sarah Cannon Research Institute
2016-2024
Cancer Institute (WIA)
2024
The University of Texas MD Anderson Cancer Center
2024
RIKEN BioResource Research Center
2023
Janssen (Belgium)
2020
AstraZeneca (France)
2020
Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.
No systemic therapies have been approved for the treatment of advanced cutaneous squamous-cell carcinoma. This cancer may be responsive to immune therapy, because mutation burden tumor is high and disease risk strongly associated with immunosuppression. In dose-escalation portion phase 1 study cemiplimab, a deep durable response was observed in patient metastatic carcinoma.We report results cemiplimab expansion cohorts patients locally or carcinoma, as well pivotal 2 cohort...
Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C, inhibits KRAS-dependent signaling. demonstrated pronounced tumor regression 17 26 (65%) KRASG12C-positive cell line- patient-derived xenograft models from multiple types, objective responses observed patients with lung colon...
RET fusions are oncogenic drivers in 1 to 2% of non-small-cell lung cancers (NSCLCs). In patients with fusion-positive NSCLC, the efficacy and safety selective inhibition unknown.We enrolled advanced NSCLC who had previously received platinum-based chemotherapy those were untreated separately a phase 1-2 trial selpercatinib. The primary end point was an objective response (a complete or partial response) as determined by independent review committee. Secondary points included duration...
Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity had an acceptable adverse-event profile the phase 1–1b part of KRYSTAL-1 1–2 study.
Abstract Purpose: The molecular epidemiology of most EGFR and KRAS mutations in lung cancer remains unclear. Experimental Design: We genotyped 3,026 adenocarcinomas for the major (exon 19 deletions L858R) (G12, G13) examined correlations with demographic, clinical, smoking history data. Results: were found 43% never smokers 11% smokers. occurred 34% 6% In patients histories up to 10 pack-years, predominated over KRAS. Among former cancer, multivariate analysis showed that, independent...
Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring glycine-to-cysteine amino acid substitutions at codon 12 (KRAS
Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti–programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non–small-cell lung cancer (NSCLC) across lines therapy. Patients were selected on basis PD-L1 expression tumor cells (TC) or tumor-infiltrating immune (IC). and Methods Eligible patients had advanced-stage NSCLC, no CNS metastases, zero two more prior chemotherapy. whose tumors expressed using SP142 immunohistochemistry assay ≥ 5% TC IC...
Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell lung cancers (NSCLCs) are effectively treated with ALK tyrosine inhibitors (TKIs). However, clinical outcomes in these patients vary, and the benefit of TKIs is limited as a result acquired resistance. Emerging data suggest that fusion variant may affect outcome, but molecular basis for this association unknown. Patients Methods We identified 129 ALK-positive NSCLC known variants. resistance mutations on were...
EGFR mutations underlie the sensitivity of lung cancers to erlotinib and gefitinib can occur in any patient with this illness. Here we examine frequency smokers men.We determined characterized their association cigarette smoking status male sex.We tested 2,142 adenocarcinoma specimens for presence exon 19 deletions L858R. were found 15% tumors from former (181 1,218; 95% CI, 13% 17%), 6% current (20 344; 4% 9%), 52% never (302 580; 48% 56%; P < .001 ever v smokers). or represented 40% all...
PURPOSE The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D CT) (D versus alone (CT) in first-line metastatic non–small-cell lung cancer (mNSCLC). METHODS Patients (n = 1,013) with EGFR/ ALK wild-type mNSCLC were randomly assigned (1:1:1) to 75 mg 1,500 platinum-based for up four 21-day cycles, followed by once every 4 weeks until progression one additional dose; progression; or six cycles (with without maintenance pemetrexed; all arms)....
9503 Background: The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK in multiple cancers, including NSCLC. In phase I study (GO30103), co-inhibition of PD-L1 signaling with tira plus atezo CIT-naïve positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR PD-L1/PD-1 inhibitors. We conducted this II trial confirm the efficacy safety (TA) placebo (PA) 1L (GO40290, NCT NCT03563716). Methods: This...
Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRASG12C. We report results from a phase I/IB study adagrasib in non-small-cell lung cancer, colorectal and other solid tumors harboring the KRASG12C mutation.Patients with advanced KRASG12C-mutant were treated 150 mg orally once daily, 300 600 1,200 or twice day using accelerated titration design, which transitioned to modified toxicity probability interval design when predefined degree was observed...
Tarlatamab, a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 and CD3, showed promising antitumor activity in phase 1 trial patients with previously treated small-cell lung cancer.In this 2 trial, we evaluated the safety of tarlatamab, administered intravenously every weeks at dose 10 mg or 100 mg, cancer. The primary end point was objective response (complete partial response), as assessed by blinded independent central review according to Response Evaluation Criteria...
9017 Background: Immune checkpoint inhibitor (ICPI) therapies, including nivolumab and pembrolizumab, have been FDA-approved in squamous non-squamous non-small cell (LC). Current IHC based diagnostics are challenged by assay slide scoring issues, more robust comprehensive biomarkers of ICPI efficacy needed. Methods: Comprehensive genomic profiling (CGP) was performed on FFPE specimens during the course clinical care. TMB (mutations/Mb) assessed as number somatic, coding, base substitution...
PURPOSE Small-cell lung cancer (SCLC) is an aggressive malignancy with limited treatments. Delta-like ligand 3 (DLL3) aberrantly expressed in most SCLC. Tarlatamab (AMG 757), a bispecific T-cell engager molecule, binds both DLL3 and CD3 leading to T-cellb–mediated tumor lysis. Herein, we report phase I results of tarlatamab patients PATIENTS AND METHODS This study evaluated relapsed/refractory The primary end point was safety. Secondary points included antitumor activity by modified RECIST...
Receptor tyrosine-protein kinase ERBB3 (HER3) is expressed in most EGFR-mutated lung cancers but not a known mechanism of resistance to EGFR inhibitors. HER3-DXd an antibody-drug conjugate consisting HER3 antibody attached topoisomerase I inhibitor payload via tetrapeptide-based cleavable linker. This phase I, dose escalation/expansion study included patients with locally advanced or metastatic non-small cell cancer (NSCLC) prior tyrosine (TKI) therapy. Among 57 receiving 5.6 mg/kg...
Affinity-optimized T cell receptors can enhance the potency of adoptive therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous therapy targeting melanoma-associated antigen A4 (MAGE-A4), cancer/testis expressed at varying levels in multiple solid tumors. We conducted multicenter, dose-escalation, phase 1 trial patients with relapsed/refractory metastatic tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head neck (...
Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to epidermal growth factor receptor 3 (HER3) attached topoisomerase I inhibitor payload via stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety HER3-DXd in patients with (