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1.
ESMO Open ; 8(4): 101589, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37385154

RESUMO

BACKGROUND: Sasanlimab is an antibody to the programmed cell death protein 1 receptor. We report updated data of subcutaneous sasanlimab in non-small-cell lung cancer (NSCLC) and urothelial carcinoma dose expansion cohorts from a first-in-human phase Ib/II study. PATIENTS AND METHODS: Patients were ≥18 years of age with NSCLC or urothelial carcinoma, and no prior immunotherapies, who progressed on or were intolerant to systemic therapy, or for whom systemic therapy was refused or unavailable. Patients received subcutaneous sasanlimab at 300 mg every 4 weeks (q4w). Primary objectives were to evaluate safety, tolerability, and clinical efficacy by objective response rate (ORR). RESULTS: Sixty-eight and 38 patients with NSCLC and urothelial carcinoma, respectively, received subcutaneous sasanlimab. Overall, sasanlimab was well tolerated; 13.2% of patients experienced grade ≥3 treatment-related adverse events. Confirmed ORR was 16.4% and 18.4% in the NSCLC and urothelial carcinoma cohorts, respectively. ORR was generally higher in patients with high programmed death-ligand 1 (PD-L1) expression (≥25%) and high tumor mutational burden (TMB; >75%). In the NSCLC and urothelial carcinoma cohorts, median progression-free survival (PFS) was 3.7 and 2.9 months, respectively; corresponding median overall survival (OS) was 14.7 and 10.9 months. Overall, longer median PFS and OS correlated with high PD-L1 expression and high TMB. Longer median PFS and OS were also associated with T-cell inflamed gene signature in the urothelial carcinoma cohort. CONCLUSIONS: Subcutaneous sasanlimab at 300 mg q4w was well tolerated with promising clinical efficacy observed. Phase II and III clinical trials of sasanlimab are ongoing to validate clinical benefit. Subcutaneous sasanlimab may be a potential treatment option for patients with NSCLC or urothelial carcinoma.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células de Transição , Neoplasias Pulmonares , Neoplasias da Bexiga Urinária , Humanos , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células de Transição/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adolescente , Adulto
2.
Cancer Chemother Pharmacol ; 84(4): 839-847, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31428820

RESUMO

PURPOSE: Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and safety measures. METHODS: Following neoadjuvant treatment and surgery, patients received adjuvant CT-P6 or trastuzumab (6 mg/kg) every 3 weeks for ≤ 1 year. RESULTS: In total, 271 and 278 patients received CT-P6 and trastuzumab, respectively. pCR and breast pCR rates were comparable between treatment groups regardless of age, region, or clinical stage. Overall, 47.6% (CT-P6) and 52.2% (trastuzumab) of patients experienced study drug-related treatment-emergent adverse events (TEAEs), including 17 patients reporting heart failure (CT-P6: 10; trastuzumab: 7). Two CT-P6 and three trastuzumab patients discontinued adjuvant treatment due to TEAEs. CONCLUSION: Adjuvant CT-P6 demonstrated comparable efficacy and safety to trastuzumab at 1 year in patients with HER2-positive EBC, supporting CT-P6 and trastuzumab comparability.


Assuntos
Medicamentos Biossimilares , Neoplasias da Mama/tratamento farmacológico , Insuficiência Cardíaca , Trastuzumab , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/farmacocinética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Monitoramento de Medicamentos/métodos , Feminino , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Receptor ErbB-2/antagonistas & inibidores , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do Tratamento
3.
Ann Oncol ; 29(4): 917-923, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29401246

RESUMO

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. Clinical trials.gov: NCT01991210.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doxorrubicina/análogos & derivados , Imunoconjugados/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/efeitos adversos , Anticorpos Monoclonais Humanizados/química , Biomarcadores/metabolismo , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/efeitos adversos , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Neoplasias Ovarianas/metabolismo , Polietilenoglicóis/uso terapêutico , Análise de Sobrevida
4.
Folia Biol (Praha) ; 63(2): 78-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28557709

RESUMO

The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574. None of the studied SNPs was associated with GIST time to progression. No significant correlation between any specific variant and time to progression was found in the group with KIT exon 11 mutation. However, individuals of at least three potentially unfavourable genotypes presented significantly shorter time to progression in comparison to patients with two or less unfavourable genotypes.


Assuntos
Antineoplásicos/uso terapêutico , Sistema Enzimático do Citocromo P-450/genética , Tumores do Estroma Gastrointestinal/genética , Proteínas Carreadoras de Solutos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Éxons/genética , Feminino , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo de Nucleotídeo Único/genética
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