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Item Dose expansion data from iintune-1, a phase 1/2 study of the STING agonist dazostinag plus pembrolizumab as first-line (1L), in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (RM-SCCHN).(2025)6020Background: Checkpoint inhibitors (CPIs) such as pembrolizumab (pembro) can lead to improved outcomes and durable responses in patients (pts) with RM-SCCHN. However, only a subset of pts with RM-SCCHN experience this benefit, and an unmet need for better treatments remains. STimulator of INterferon Genes (STING) agonism enhanced the response to CPIs preclinically. Dazostinag (dazo) is a small molecule STING agonist that has shown antitumor activity and activation of innate and adaptive immune responses in pts with solid tumors in the dose escalation part of iintune-1, with a recommended dose for expansion of 5 mg in combination with pembro. We report data from the ongoing dose expansion cohort 2A of iintune-1 in the first 30 pts with incurable 1L RM-SCCHN with a PD-L1 combined positive score (CPS) >=1, treated with dazo in combination with pembro (NCT04420884). Method(s): Pts receive dazo 5 mg IV on Days 1, 8, 15 plus pembro 200 mg IV on Day 1, in 21-day cycles. Primary endpoints are safety and tolerability. Secondary endpoints include investigator-assessed overall response rate (ORR) per RECIST 1.1 and duration of response (DOR). Dose optimization is planned as part of expansion. Result(s): As of Dec 16, 2024, 30 pts had been enrolled and received treatment. Median age was 64 years and 73% of pts were male. The most common primary tumor locations were oral cavity (n=10, 33%), oropharynx (n=8, 27%), and larynx (n=6, 20%). Median CPS score was 13.5 (range, 1-101). A median of 4.5 treatment cycles (range 1-15) were received. Treatment-emergent adverse events (TEAEs) occurred in all pts (grade >=3 in 37%); the most common were fatigue (40%), nausea (27%), cough (23%), and headache (20%). Dazo-related TEAEs occurred in 80% of pts (grade >=3 in 13%); the most common was fatigue (30%). Cytokine release syndrome was reported in 4 pts (13%; all dazo-related and grade 1-2). TEAEs led to dazo discontinuation in 1 pt. No treatment-related deaths were reported. Among 29 response-evaluable pts, 1 had a confirmed complete response and 7 had confirmed partial responses (+2 unconfirmed), for an ORR of 34%. Median DOR was not reached. Pharmacodynamic analyses revealed biomarker changes consistent with the expected mechanism of action and dose escalation data, including induction of a STING gene signature, cytokine induction, peripheral immune cell activation and CD8+ T cell recruitment to the tumor. Analyses of changes in peripheral ctDNA pre- and post-treatment are ongoing. Conclusion(s): This early study of dazo 5 mg IV in combination with pembro showed a manageable safety profile with an encouraging ORR in pts with RM-SCCHN. Pharmacodynamic findings demonstrate peripheral and intratumor changes consistent with STING agonism. Clinical trial information: NCT04420884.Item OrigAMI-3: A randomized, phase 3 study of amivantamab plus FOLFIRI vs cetuximab or bevacizumab plus FOLFIRI in participants with recurrent, unresectable, or metastatic RAS/BRAF wild-type colorectal cancer.(2025)TPS3638Background: Among patients with metastatic colorectal cancer (mCRC), approximately 50% are wild-type for KRAS, NRAS, and BRAF (RAS/BRAF WT) without actionable genomic alterations. Standard first-line therapy for RAS/BRAF WT mCRC is 5-FU-based doublet chemotherapy (FOLFOX or FOLFIRI) plus anti-EGFR or anti-VEGF therapy. The choice of second-line treatment is dependent on first-line treatment (eg, oxaliplatin-based chemotherapy in the first-line necessitates irinotecan-based in the second-line, and vice versa). Known resistance mechanisms to anti-EGFR therapy are MET alterations, with MET amplification occurring in 5%-23% of EGFR-resistant mCRC and increasing in prevalence over subsequent lines of therapy. Amivantamab is an EGFR-MET bispecific antibody with immune cell-directing activity and is FDA-approved for 4 indications in EGFR-mutated advanced non-small cell lung cancer. In the phase 1b/2 OrigAMI-1 study (NCT05379595), amivantamab plus FOLFIRI demonstrated promising antitumor activity, independent of line of therapy, in participants (pts) with RAS/BRAF WT mCRC without prior anti-EGFR exposure (Pietrantonio ESMO 2024). The objective of this phase 3 randomized study is to assess the efficacy of amivantamab plus FOLFIRI vs cetuximab or bevacizumab plus FOLFIRI, as second-line therapy for pts with recurrent RAS/BRAF WT mCRC. Method(s): The global OrigAMI-3 study (NCT06750094) is planned to open in 230 sites in 25 countries. Eligible pts will be WT for KRAS, NRAS, and BRAF, have recurrent unresectable or mCRC, and must have had disease progression on one prior line of systemic therapy for metastatic disease (prior regimen must be fluoropyrimidine-based and oxaliplatin-based therapy). Pts with treated, stable, and asymptomatic brain metastases are allowed. Key exclusion criteria include known dMMR/MSI-H status without prior immunotherapy, HER2-positive or amplified tumor, and prior exposure to irinotecan or agents targeting EGFR or MET. Approximately 700 pts will be randomly assigned 1:1 to receive subcutaneous amivantamab (co-formulated with recombinant human hyaluronidase [rHuPH20]) plus FOLFIRI vs intravenous cetuximab or bevacizumab (investigator's choice, per local guidelines) plus FOLFIRI. Randomization will be stratified by choice of cetuximab or bevacizumab, primary tumor location (left vs right-sided), duration of first-line therapy (< 6 months or >=6 months), and prior anti-VEGF therapy (yes or no). The dual primary endpoints will be progression-free survival by blinded independent central review and overall survival. Secondary endpoints include objective response rate, duration of response, and patient-reported outcomes. Safety assessments will include monitoring adverse events and laboratory abnormalities. Clinical trial information: NCT06750094.Item Nodes of Contention: The Role of Lymphadenectomy in Adrenocortical Cancer Management.(2026)Adrenocortical carcinoma (ACC) is a rare, aggressive endocrine malignancy with poor survival outcomes and high recurrence rates. Whilst surgical resection is the cornerstone of curative treatment, the role of lymphadenectomy remains debated. "Nodes of contention" in ACC management center on balancing accurate staging and potential oncologic benefit against added operative time, complexity, and morbidity. We reviewed the available published literature over the last 20 years, including retrospective series, to evaluate the prognostic and therapeutic significance of lymphadenectomy in ACC. Though systematic lymph node dissection improves staging accuracy and may identify patients at higher risk who could benefit from adjuvant therapy, evidence demonstrating a survival benefit is inconsistent. This is largely due to the rarity of the condition, heterogeneity in surgical approaches, and lack of standardized nodal templates. Concerns regarding increased operative morbidity further limit widespread adoption. This review synthesizes current evidence on nodal assessment in ACC and highlights gaps in prospective data. While nodal involvement is a strong prognostic factor, the therapeutic impact of lymphadenectomy remains unclear. Prospective, multicenter trials are urgently needed to define its role in ACC management.Item Implementing the Person-Environment-Occupation-Performance model in an occupational therapy neurosciences service: A mixed methods study.(2026)Introduction: Using models of occupation in occupational therapy can promote professional identity and self-efficacy. This study evaluated implementing the Person-Environment-Occupation-Performance Model (PEOP) in a neurosciences occupational therapy service in the United Kingdom. Methodology: A mixed-methods approach with four stages. 1: survey of conceptual models in practice; 2: conceptual model teaching followed by focus groups; 3: PEOP training followed by implementation and Community of Practice; 4: individual semi-structured interviews. Participants were occupational therapists working in a neurosciences service. Finding(s): The survey identified limited use of conceptual models in practice. Participants chose the PEOP model due to congruence with practice, model semantics and potential to reinforce professional identity. Following training, therapists reported increased knowledge and confidence in using the model. During implementation, data from the community of practice created three themes: feasibility of application, documentation is key to change, keeping it meaningful. Follow-up interviews after 3-months generated three themes: PEOP legitimises the occupational therapist's role, communities of practice spark change, the model supports occupational adaptation. Conclusion(s): Implementing the PEOP model was feasible and impactful. Training improved knowledge and confidence, and the community of practice and modified documentation supported application. Implementation realised continuity of occupation-centred practice across patient pathways and enhanced professional identity.Item Operationalising Genomic Surveillance for Antimicrobial Resistance in Low- and Middle-Income Countries: A One Health Perspective from Bangladesh.(2026)Antimicrobial resistance (AMR) represents a critical global health challenge, with low- and middle-income countries (LMICs) disproportionately affected due to limited surveillance capacity. Advances in microbial genomics offer powerful tools for AMR detection and monitoring; however, translating these technologies into sustainable, policy-relevant surveillance systems in resource-constrained settings remains challenging. This review synthesises current approaches to genomic surveillance of AMR in LMICs and presents Bangladesh as a case study to illustrate how genomic, environmental, and clinical data can be integrated within a One Health framework. We examine key barriers to implementation, including laboratory infrastructure, bioinformatics capacity, data governance, and cross-sector coordination, alongside emerging opportunities for capacity building and regional collaboration. Using Bangladesh as a case study, we highlight practical pathways for embedding genomic surveillance into national AMR strategies, integrating human, animal, and environmental reservoirs of antibiotic resistance. We argue that genomic surveillance can move beyond data generation to inform infection prevention, antibiotic stewardship, and public health decision making when supported by context-appropriate infrastructure and interdisciplinary engagement. By focusing on operational and translational considerations rather than technology alone, this review provides actionable insights for microbiologists, public health practitioners, and policymakers seeking to strengthen AMR surveillance systems in LMICs through a One Health approach.
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