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D. Kowalski



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    ORAL 01 - Chemotherapy Developments for Lung Cancer (ID 88)

    • Event: WCLC 2015
    • Type: Oral Session
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      ORAL01.05 - Phase I/II Dose Escalation Study of Immunoconjugate L-DOS47 as a Monotherapy in Non-Squamous Non-Small Cell Lung Cancer Patients (ID 3272)

      10:45 - 12:15  |  Author(s): D. Kowalski

      • Abstract
      • Presentation
      • Slides

      Background:
      L‑DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, is a protein conjugate consisting of a urease conjugated to a camelid monoclonal antibody (AFAIKL2) that is targeted to the CEACAM6 antigenic tumour marker. The AFAIKL2 antibody serves as a targeting agent to deliver the enzyme to the tumor sites while the urease enzyme converts urea, an abundant natural metabolite, into ammonia and generates a local pH increase. The combined effect of ammonia toxicity and pH increase is cytotoxic to cancer cells in culture and in xenograft models. This first in human study of L‑DOS47 was designed to define the maximum tolerated dose of multiple doses of L-DOS47 administered intravenously to patients with non-squamous NSCLC when given as a monotherapy.

      Methods:
      Stage IIIb or IV histologically confirmed non-squamous NSCLC patients (aged ≥18 yrs, ECOG PS ≤2) receive multiple cycles of L-DOS47 during the study treatment period. L-DOS47 is administered once weekly over 14 days followed by 7 days rest in each treatment cycle. Patients are recruited into cohorts and received the same dose of L-DOS47 on Days 1 and 8 of each treatment cycle. Dose levels of L-DOS47 are escalated in further cohorts following a review of safety data by the Trial Steering Committee.

      Results:
      Thirty-three (33) pts (median age 61, 58% male) were enrolled in the first ten cohorts (dose levels: 0.12, 0.21, 0.33, 0.46, 0.59, 0.78, 1.04, 1.38, 1.84, 2.45 µg/kg) in four Polish centers. L-DOS47 was well tolerated at the dose levels reviewed. No DLTs were reported. Adverse events reported to date were expected for the population under study. None of the patients treated to date have had a partial or complete response as defined by RECIST v1.1. Sixteen (16) patients had an overall response of stable disease after completing two cycles of L-DOS47. One patient in cohort 9 was dosed for 9 cycles without disease progression.

      Conclusion:
      L-DOS47 monotherapy is well tolerated at dose levels up to 2.45 µg/kg. ClinicalTrials.gov identifier: NCT02340208

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    P1.06 - Poster Session/ Screening and Early Detection (ID 218)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P1.06-007 - Plasma Circulating MicroRNA-944 and MicroRNA-3662 as Novel Histologic Type-Specific Lung Cancer Biomarkers (ID 521)

      09:30 - 17:00  |  Author(s): D. Kowalski

      • Abstract
      • Slides

      Background:
      Altered expression of microRNAs is associated with development and invasion of cancers by regulating post-transcriptionally gene function. Possibility of detection of circulating miRNAs expression in patients’ plasma or serum make them valuable biomarkers of different neoplasms, such as lung cancer.

      Methods:
      We investigated potential role of miR-944 and miR-3662 expression analysis as a novel lung cancer biomarkers and their lung tumor specificity in plasma samples of 90 lung cancer patients (40 NSCLC patients in stage IA-IIIA and 20 NSCLC patients in stage IIIB-IV; 8 SCLC patients with limited and 22 SCLC patients with extensive disease) and 85 healthy individuals using qRT-PCR analysis.

      Results:
      Expression of miR-944 and miR-3662 was significantly upregulated in lung cancer patients in comparison to healthy individuals. Higher stage of lung cancer correlated with higher miRNAs expression (Figure 1). Receiver operating curves (ROC) analysis have presented diagnostic power of analysis of both miRNAs expression for detection of patients with I and II stage of NSCLC with area under curve (AUC) of 0.881. Moreover, miR-944 has shown diagnostic accuracy for operable squamous cell carcinoma detection (AUC=0.982) whereas miR-3662 - for operable adenocarcinoma (AUC=0.926) (Figure 2).Figure 1Figure 2





      Conclusion:
      Our research is a first study investigating the plasma expression of miR-944 and miR-3662 in patients with neoplasms and in healthy individuals. Moreover, this is a first study that described a miR-3662 expression. We have shown that examination of these two miRNAs may be considered as a tool for NSCLC early diagnosis as well as for non-invasive diagnosis of lung cancer late stages. Studied miRNAs have also shown high utility in detection of histological type-specific NSCLC subtypes, such as adenocarcinoma and squamous-cell carcinoma.

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