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Philip J Jewsbury
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-07 - Open-Label, Biomarker-Directed Platform Study in NSCLC Patients Who Progressed on an Anti-PD-(L)1-Containing Therapy (HUDSON) (ID 643)
10:15 - 18:15 | Author(s): Philip J Jewsbury
- Abstract
Background
Immune checkpoint inhibitor (ICI)-containing regimens have significantly improved survival outcomes in first- and second-line non-small cell lung cancer (NSCLC). However, few patients have-durable responses to anti-programmed cell death‑1/programmed cell death-ligand 1 (anti-PD-[L]1)-containing therapy (primary resistance) or other patients progress during anti-PD-(L)1-containing therapy (acquired resistance). HUDSON addresses the urgent need to identify new treatments and understand ICI resistance for patients who progressed after receiving anti-PD-(L)1-containing therapy.
Method
HUDSON is a multi-centre, international, multi-arm, platform study (NCT03334617), which will 1) evaluate therapies to reverse ICI resistance and 2) define mechanisms of ICI resistance in patients with NSCLC who have progressed following standard-of-care platinum- and ICI-based therapies. HUDSON consists of biomarker matched and non-matched groups (Figure). Allocation is guided by tumour molecular profile, using a pre-specified algorithm. Pre-existing local next generation sequence (NGS) data enables rapid patient allocation to biomarker-matched groups. Central molecular profiling comprises NGS and immunohistochemistry data. New groups will be added as new translational hypotheses emerge. Translational research will employ serial peripheral blood samples (including ctDNA) and tumour biopsies.
Figure. Study design and biomarker prevalence
Result
Enrolment is ongoing; as of 01 April 2019, patients have been dosed in each of the drug combinations currently open for recruitment. Analyses of tissue and blood samples collected for exploratory research are ongoing, including genomic, transcriptomic and chemistry biomarkers such as tumour mutation burden, human leukocyte antigen status, T-cell receptor repertoire, and peripheral immune activation signatures.
Conclusion
Specific differences between patients on individual HUDSON arms that inform anti-PD(L)1 resistance mechanisms, plus learnings from the implementation of this innovative and complex platform study will be presented.
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P2.01-22 - ORCHARD: A Phase II Platform Study in Patients with Advanced NSCLC Who Have Progressed on First-Line Osimertinib Therapy (ID 1303)
10:15 - 18:15 | Author(s): Philip J Jewsbury
- Abstract
Background
Osimertinib is a third-generation, central nervous system (CNS)-active, irreversible epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising mutations (EGFRm) and EGFR T790M. First-line osimertinib has demonstrated superiority in progression-free survival (PFS) compared with first-generation EGFR-TKIs in patients with EGFRm advanced NSCLC (Soria et al, NEJM 2018). The most common resistance mechanisms to first-line osimertinib identified from plasma samples are MET amplification (15%) and EGFR C797S (7%) (Ramalingam et al, Ann Oncol 2018). Further clinical studies are needed to better understand resistance mechanisms and evaluate post-progression targeted treatment options.
Method
ORCHARD is an open-label, multicentre, biomarker-directed, Phase II platform study evaluating the optimal treatment for individual patients with EGFRm NSCLC depending on their underlying resistance mechanism to first-line osimertinib.
Adult patients with EGFRm locally advanced/metastatic NSCLC and radiological progression on first-line osimertinib monotherapy will be eligible.
Treatment assignment will be based on molecular characterisation of the tumour at progression from a mandatory tissue biopsy.
ORCHARD will comprise of three groups assigned by tumour molecular profile (Figure). An adaptive design allows addition of new treatments based on emerging findings. Tumour assessments (RECIST 1.1) will be performed every 6 weeks for the first 24 weeks and every 9 weeks thereafter until progression. An interim analysis of each cohort will be performed when ≈16 patients have reached the second on-treatment RECIST assessment. Based on preliminary signals, the cohort may be stopped or expanded to 30–40 patients for further evaluation.
The primary outcome is investigator-assessed objective response rate; secondary outcomes include PFS, duration of response, overall survival, and pharmacokinetics of each treatment module, evaluated independently. Exploratory outcomes include tumour and plasma biomarker and resistance analyses, and correlation between biomarker profiles and treatment effect. Safety data will also be reported.
Result
Section not applicable
Conclusion
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