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Crispin Hiley
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-43 - PD-RAD: A Translational Study Investigating PD-L1 Expression After Radiotherapy for Non-Small Cell Lung Cancer - Trial in Progress (ID 1811)
09:45 - 18:00 | Author(s): Crispin Hiley
- Abstract
Background
Radiotherapy (RT) is delivered to 30-50% of NSCLC patients. However, over half of patients progress following RT and mechanisms of resistance are poorly understood. RT has immune-modulatory properties such as the ability to upregulate tumour PD-L1 expression and can recalibrate the immune contexture. Blockade of the PD-1/PD-L1 axis has been shown to enhance the efficacy of RT in several pre-clinical models and the recent PACIFIC trial. Exploiting immuno-regulatory effects of RT therefore has the ability to enhance local and distant anti-cancer effects of RT, especially when combining RT with immunotherapies such as anti-PD-1 or costimulatory agonists.
Method
PDRAD is a prospective UK multi-centre feasibility study of paired pre- and post-treatment biopsies in NSCLC patients receiving palliative or radical RT. The study will recruit up to 30 patients with inoperable disease that is accessible to core biopsy by CT or bronchoscopy within the proposed RT field. Patients with archival baseline histology containing sufficient tumour material are eligible. Consented patients undergo a repeat biopsy in the second week of RT (fig.1). Blood samples will be collected at baseline, repeat biopsy, and following RT to assess immune changes that may correlate with the tumour microenvironment (TME). PDRAD opened to recruitment in November 2018 and will continue recruitment over 16 months.
Research aims include investigating:
Feasibility and acceptability of obtaining paired biopsies
Changes in the immune contexture in irradiated tumour and ‘out of field’ sites
Immune changes in the TME and peripheral blood
Interim feasibility results after recruitment of 15 patients will be presented at World Lung.
Result
Section not applicable
Conclusion
We are at a pivotal point in evolving our knowledge of how the TME may influence responses to RT. The PDRAD study will help to influence further clinical trials, including combination studies with immunotherapies and predictive and prognostic biomarker development within the field.
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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
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-08 - Clinical Trial in Progress: CONCORDE - A Phase 1B Study of Novel Agents in Combination with Conventional Radiotherapy in NSCLC (ID 600)
10:15 - 18:15 | Author(s): Crispin Hiley
- Abstract
Background
The majority of patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative intent receive radiotherapy (RT) as part of their treatment. Despite considerable technological advances in RT delivery, the survival of these patients has barely changed over the last 60 years. A major factor in this failure to improve outcomes is the relative radioresistance of NSCLC. Attempts to overcome radioresistance by escalating RT doses have demonstrated inferior outcome likely secondary to normal tissue toxicity. Therefore an alternate approach is to exploit genetic dependencies in the DNA damage response of NSCLC, using biological inhibitors to selectively radiosensitise tumours whilst sparing normal tissues. The CONCORDE study is a multi-arm phase 1B platform study to investigate the combination of radical RT with DNA damage response inhibitors (DDR-i) targeting five different proteins: PARP, ATR, WEE1, ATM, DNA-PK.
Method
CONCORDE is a hypothesis-driven combination study of novel therapeutics and RT using an innovative adaptive early-phase trial design. The study will address two main research questions:
- What are the recommended phase 2 doses (RP2D) of individual DDR-i in combination with curative RT in patients with stage IIB/III NSCLC?
- What are the safety profiles of individual DDR-i combined with curative RT in this population?
Key inclusion criteria are stage IIB and III NSCLC planned to receive curative intent RT doses (+/- neoadjuvant chemotherapy) and PS 0-1. Participants will be randomised on a 3:1 basis between DDR-i with RT or RT alone. Patients receiving RT alone will be pooled across the arms to provide contemporary data on toxicity. All patients will receive external beam RT with a planned dose of 60 Gy in 30 fractions.
The study will use a Bayesian adaptive model-based approach to dose-escalation, with separate Time-To-Event Continual Reassessment Method (TiTE-CRM) models in each experimental arm. The primary endpoints are dose-limiting toxicities occurring within 12 months of the start of radiotherapy. Secondary endpoints include safety and toxicity (acute and late toxicity up to 2 years including using patient reported outcome (PRO) measures), treatment compliance, and best overall response (using RECIST 1.1, progression-free, and overall survival).
Correlative studies will be carried out to identify biomarkers of toxicity and response. We have secured high-level agreement from leading pharmaceutical partners to invest in 5 treatment arms and funding approval from Cancer Research UK is pending. The first participant is estimated to commence treatment in late 2019
Result
Section not applicable
Conclusion
Section not applicable
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P2.01-25 - TOURIST: Thoracic Umbrella Radiotherapy Study in Stage IV NSCLC: A Phase III Randomized Trial in Development (Now Available) (ID 1024)
10:15 - 18:15 | Author(s): Crispin Hiley
- Abstract
Background
Non Small Cell Lung Cancer (NSCLC) is the leading cause of cancer mortality throughout the world with an incidence exceeding 1.2 million. 70% of NSCLC patients present with incurable disease with treatment aimed at alleviating symptoms, maintaining / improving quality of life as well as prolonging survival.
In the last decade there have been dramatic changes in systemic therapy (chemotherapy, immunotherapy, Tyrosine kinase Inhibitors (TKIs)). Despite these advances, many patients suffer from lororegional symptomatic relapse. This may benefit from local radiotherapy in addition to other standards of care such as symptom control. Radiotherapy remains widely used in the management of stage IV NSCLC but strategies vary hugely because the data originates from a series of dose fractionations trials in the 1990s when systemic therapy options were limited.
There is therefore limited evidence regarding the use and place of palliative radiotherapy in conjunction with modern systemic treatments and there is a need to assess benefits of advanced radiotherapy techniques in this population. The TOURIST trial aims to establish the utility of palliative thoracic radiotherapy in the primary treatment of stage IV NSCLC.
Method
This is a phase III platform that currently has 2 study arms, to cover the needs of differing patient populations, defined by the use of first line systemic therapy.
Study 1 (PRINCE) Patients receiving first line systemic therapy as standard of care, who have not progressed after 2-4 cycles are randomised 1:1 to either high dose palliative radiotherapy to the thorax, or to no radiotherapy while continuing on their standard systemic therapy. Co-primary endpoints: overall survival, PROMs recorded QOL, with progression free survival and time to next line of therapy, as secondary endpoints.
Study 2 (QUARTZ Lung) Asymptomatic patients unsuitable for standard systemic therapy randomised 1:1 to low dose palliative radiotherapy dose to the thorax or no radiotherapy. Telephone follow up will be used for PROMs data collection to measure QOL improvements.
Stratification factors for both studies will include bulk of thoracic disease, use of advanced radiotherapy techniques and performance status. The TOURIST trial intends to recruit 750 patients and is anticipated to open in 2020.
Result
Section not applicable
Conclusion
Section not applicable
