REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers

Merrick, Sophie; Nankivell, Matthew; Quartagno, Matteo; Clarke, Caroline S.; Joharatnam‐Hogan, Nalinie; Waddell, Tom; O’Carrigan, Brent; Seckl, Michael J.; Ghorani, Ehsan; Banks, Emma; Edmonds, Kim; Bray, George A.; Woodward, Rose; Bennett, R. Avery; Badrock, Jonathan; Hudson, Will G.; Langley, Ruth E.; Vasudev, Naveen S.; Pickering, Lisa; Gilbert, D

doi:10.1016/j.cct.2022.107030

Cited by 5 publications

(3 citation statements)

References 22 publications

(24 reference statements)

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“…The scores of Cancer Trial Organisations on metrics assigned to each component of climate change commitment are presented in Table 1. With maximum obtainable score of 6 points (100%), the total scores of each cancer trial organisation ranged from 0 to 6 (0- treatment schedules [9][10][11][12], and their collaborative nature offer the potential for less redundancy in cancer discovery [13,14]. Their focus on translating laboratory-based discovery into clinical care integrates them with a community where climate smart initiatives such as "My Green Lab" are already successfully embedded [15].…”

Section: Resultsmentioning

confidence: 99%

Climate Change Advocacy and Cancer Clinical Trial Organisations

Myoo,

weadick,

murphy

et al. 2024

Preprint

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Climate change is a threat to human health; equally health care is a threat to climate change as it accounts for 4% of greenhouse gas emissions and 30% of the world’s electronically stored data. 350,000 international trials are registered on ClinicalTrials.gov with ~ 27·5 million tonnes of emissions (equivalent to half of annual Danish emissions). In September 2023 we assessed climate awareness among cancer clinical trial organisations via a web-based scoping exercise. Seventy-five organisations were identified of whom 46 had search tools on their websites. Eight out of 46 clinical trial groups had at least one parameter of commitment to climate change, and 38 organisations had none. Of 46 websites, 5 had climate change position statements or policies, 4 had a committee or task force, 1 provided patient education resources for climate change via video link, 7 included green initiative advice and 8 had publications addressing climate change. Only 5 were listed as members of Climate Change Consortiums. Based on website assessment climate advocacy among cancer clinical trial organisations is low, and efforts to encourage climate engagement are needed.

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Section: Resultsmentioning

confidence: 99%

Climate Change Advocacy and Cancer Clinical Trial Organisations

Myoo,

weadick,

murphy

et al. 2024

Preprint

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Section: Optimal Frequency Of Therapymentioning

confidence: 99%

“…These efforts are exemplified by the ongoing UK NIHR portfolio phase III REFINE-Lung study 58 and the similarly designed phase II REFINE basket trial currently open for patients with renal cancer and melanoma. 59 Recognizing that there is no prior rationale for selecting any particular reduced frequency of immunotherapy administration compared to SOC, the REFINE-Lung study was designed to explore a range of pembrolizumab frequencies amongst patients with advanced NSCLC in a multi-arm study. Adapting a methodology originally designed to determine the optimal duration of antibiotic therapy of infection, 60 REFINE-Lung explores administration frequencies of 6 (SOC), 9, 12, 15 and 18 weekly treatment.…”

Section: Optimal Frequency Of Therapymentioning

confidence: 99%

What is the optimal duration, dose and frequency for anti-PD1 therapy of non-small cell lung cancer?

Kuah,

Monfries,

Quartagno

et al. 2023

Ther Adv Med Oncol

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Over the past decade, immune checkpoint inhibitors (ICIs) have transformed the management of multiple malignancies including lung cancer. However, the optimal use of these agents in terms of duration, dose and administration frequency remains unknown. Focusing on anti-PD1 agents nivolumab and pembrolizumab in the context of non-small cell lung cancer, we argue that several lines of evidence suggest current administration regimens of these drugs may result in overtreatment with potentially important implications for cost, quality of life and toxicity. This review summarizes evidence for the scope to optimize anti-PD1 regimens, the limitations of existing data and potential approaches to solve these problems including with a novel multi-arm clinical trial design implemented in the recently opened REFINE-Lung study.

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Extended duration of treatment using reduced-frequency dosing of anti-PD-1 therapy in patients with advanced melanoma and Merkel cell carcinoma

Tachiki,

Hippe,

Williams Silva

et al. 2023

Cancer Immunol Immunother

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Background Optimal duration of treatment (DoT) with immune checkpoint inhibitors (ICI) in metastatic cancers remains unclear. Many patients, especially those without radiologic complete remission, develop progressive disease after ICI discontinuation. Extending DoT with ICI may potentially improve efficacy outcomes but presents major logistical and cost challenges with standard frequency dosing (SFD). Receptor occupancy data supports reduced frequency dosing (RFD) of anti-PD-1 antibodies, which may represent a more practical and economically viable option to extend DoT. Methods We conducted a retrospective study of patients with metastatic melanoma and Merkel cell carcinoma (MCC), who received ICI at RFD administered every 3 months, after initial disease control at SFD. We evaluated efficacy, safety, and cost-savings of the RFD approach in this cohort. Results Between 2014 and 2021, 23 patients with advanced melanoma (N = 18) or MCC (N = 5) received anti-PD-1 therapy at RFD. Median DoT was 1.1 years at SFD and 1.2 years at RFD. The 3 year PFS after start of RFD was 73% in melanoma and 100% in MCC patients, which compare favorably to historical control rates. In the subset of 15 patients who received at least 2 years of therapy, total savings amounted to $1.1 million in drug costs and 384 h saved despite the extended DoT (median 3.4 years), as compared to the calculated cost of 2 years at SFD. Conclusions ICI administration at RFD can allow extension of treatment duration, while preserving efficacy and reducing logistical and financial burden. RFD approach deserves further exploration in prospective clinical trials.

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REFINE (REduced Frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers

Cited by 5 publications

References 22 publications

Climate Change Advocacy and Cancer Clinical Trial Organisations

Climate Change Advocacy and Cancer Clinical Trial Organisations

What is the optimal duration, dose and frequency for anti-PD1 therapy of non-small cell lung cancer?

Extended duration of treatment using reduced-frequency dosing of anti-PD-1 therapy in patients with advanced melanoma and Merkel cell carcinoma

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