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WHAT IS ALREADY KNOWN ON THIS TOPIC Identifying eligible patients for precision oncology clinical trials is resource-intensive and inefficient, particularly for rare molecular subpopulations. Traditional screening methods often result in high screen failure rates, financial burden and delays because investigators must consent and screen large numbers of patients without prior knowledge of their genomic status to find the few who are eligible.WHAT THIS STUDY ADDS The BASECAMP-1 study demonstrated that a bioinformatic screening approach, leveraging existing clinical next-generation sequencing data, can successfully enrol patients for precision oncology clinical trials while reducing study staff burden and resource use compared with traditional screening.HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY These findings support a shift towards using clinico-genomic database mining to initially filter patients for trials using routine clinical data rather than enrolling and then screening patients one by one. The results suggest that collaborative data-sharing between industry and academic partners can overcome the logistical hurdles of studying rare biomarkers, enabling precision oncology trials to be completed efficiently and with more diverse patient populations.Introduction The promise of precision oncology is to provide treatment tailored to the unique mutational profile of a particular patient’s tumour and the accompanying tumour microenvironment. 1 2 However, patient screening for precision oncology clinical trials can be time-consuming and financially burdensome, particularly when identifying rare study populations.3 4 Clinical trials that require identification of patients with rare molecular targets are commonly associated with high rates of screen failures and small study populations. Other challenges with screening for precision oncology studies are that patients must have adequate tumour samples for biomarker testing and results from next-generation sequencing (NGS) and/or other molecular testing can take up to 3 weeks, with further delays if archival tumour tissue retrieval is required from external pathology departments or if inadequate tumour sample is obtained. These delays often impact patient eligibility and enrolment feasibility.To address these challenges, A2 Biotherapeutics (A2 Bio) and a team of academic leaders experienced in clinical trial development designed BASECAMP-1 (NCT04981119), a non-interventional master screening study to identify patients with advanced solid malignancies who are germline heterozygous human leucocyte antigen (HLA)-A*02 and have HLA-A*02 loss of heterozygosity (LOH) in the tumour. The frequency of HLA-A LOH in advanced solid tumours is about 16%, so an efficient screening strategy is required to optimise trial candidate identification.5 6 Patients who enrol in BASECAMP-1 may be eligible for interventional studies of logic-gated Tmod chimeric antigen T-cell (CAR T) therapies, such as EVEREST-1 (NCT05736731), EVEREST-2 (NCT06051695) and DENALI-1 (NCT06682793), which require HLA-A*02 LOH for eligibility.When the BASECAMP-1 study began, eligible patients were identified using a traditional approach where investigators screened all potentially eligible patients with no prior knowledge of HLA status, first through germline DNA sequencing to determine HLA status, and subsequent tumour biopsy sequencing to determine HLA LOH status. This approach was resource-intensive for both physicians and study staff. To improve efficiency, we co-developed a second approach with Tempus AI, Inc (Tempus) the bioinformatic programme Aware that enabled data mining of NGS results from routine clinical diagnostic tests to retrospectively and prospectively identify patients at study sites with tumours that had HLA-A*02 LOH. This report describes BASECAMP-1; compares the efficiency of these two screening methods; and discusses the advantages of BASECAMP-1 beyond efficient enrolment for precision oncology clinical trials.Materials and methods BASECAMP-1 is a two-part study ( figure 1; study protocol provided in online supplemental file 1). In part 1, eligible patients are adults with a pathologically confirmed solid tumour that is metastatic, unresectable locally advanced or at high risk for incurable relapse within 2 years, at any point within their disease course, who provide informed consent. Study participants undergo germline HLA typing, which may be done with study-directed analysis or using clinically available results. If the participant is HLA-A*02 heterozygous, then their tumour sample will undergo NGS testing to determine if the tumour has HLA-A*02 LOH. Participants with a documented HLA-A*02 LOH status are enrolled in part 1 of BASECAMP-1 and are followed for 2 years to monitor their disease course. Participants with tumour-associated HLA-A*02 LOH who wish to be considered for an interventional cell therapy trial can go on to part 2 of BASECAMP-1 and undergo leukapheresis. If a participant qualifies for an allogeneic Tmod CAR T therapy, then enrolment into part 2 is not required.SP110.1136/bmjonc-2025-001033.supp1Supplementary dataFigure 1BASECAMP-1 study schema. BASECAMP-1 (NCT04981119) is a master prescreening, observational study to identify patients for the Tmod clinical trials. The main eligibility criteria for BASECAMP-1 are germline HLA-A*02 heterozygous adults with unresectable advanced or metastatic solid tumours and tumour-associated HLA-A*02 LOH. Patients in BASECAMP-1 undergo leukapheresis so their CAR T treatment can be prepared without delay when they begin the clinical trials. AE, adverse event; ECOG, Eastern Cooperative Oncology Group; HLA, human leucocyte antigen; LOH, loss of heterozygosity; NGS, next-generation sequencing; SAE, serious AE.In part 2, a participant can proceed to leukapheresis if they meet additional eligibility criteria, such as adequate bone marrow reserves to undergo leukapheresis, and they are candidates to receive an autologous CAR T therapy. The leukapheresis product is frozen and stored for use in future studies. The participant may then continue to other standard-of-care therapies or enrol in other clinical studies. Participants who undergo leukapheresis are followed for any potential serious adverse events related to leukapheresis.If the participant’s cancer relapses and they become eligible for interventional trials of logic-gated Tmod CAR T therapies, the Tmod CAR T is manufactured immediately and administered after lymphodepletion.We identify patients for BASECAMP-1 using two approaches. Using a traditional approach, investigators consent and screen patients who might be candidates for cell therapy clinical trials, without prior knowledge of the patients’ germline HLA type and tumour-associated HLA-A*02 LOH status. Participants are screened for germline HLA haplotypes to identify those who are HLA-A*02 heterozygous. Then, archival tumour tissue from these participants is individually requested from local pathology departments and distributed to Tempus for xT testing to determine their tumour-associated HLA-A*02 LOH status. Tempus xT uses tumour tissue with a matched normal sample from blood or saliva for analysis. The DNA panel detects single-nucleotide variants, insertions and/or deletions, and copy number variants in 648 genes, as well as chromosomal rearrangements in 22 genes; the test has high sensitivity and specificity.7 Not all participants with HLA-A*02 heterozygosity will have adequate available tissue capable of technically generating NGS and LOH results. Throughout this multistep process, participant samples must be tracked, and results must be efficiently communicated to ensure time delays do not adversely affect the study team and patient eligibility for the trial.To more efficiently identify potentially eligible patients, A2 Bio co-developed with Tempus the bioinformatic programme ‘Aware’. The Aware programme identifies patients with specific molecular alterations, through Tempus xT testing using a clinico-genomic database that includes linked genomic and transcriptomic sequencing, pathology and other clinical data collected during routine clinical care by Tempus (Chicago, Illinois, USA).8–13 The database contains longitudinal structured and unstructured patient-level data from various oncology settings, including integrated delivery networks, academic institutions and community practices. For BASECAMP-1, after patients undergo routine diagnostic NGS tumour analysis, Tempus runs a bioinformatic algorithm to determine the presence of LOH on all samples evaluated with xT testing.5 If a patient in the study site’s network is identified to have tumour-associated HLA-A*02 LOH, Tempus notifies the site investigator and the ordering physician that they have a potential patient for BASECAMP-1 (figure 2). The study sponsor is blinded to patient identity, both in this prescreening phase and during study enrolment. In accordance with patient consent obtained during commercial testing, Tempus routinely identifies and connects patients with relevant clinical trials. Patients and their physicians have the ability to decline participation or further communication at any time. Patients are further screened for participation and enrolment in the A2 Bio study only after signing the Part 1 consent for this study. Identified patients are still consented to BASECAMP-1, then screened and confirmed for LOH status in the BASECAMP-1 protocol.Figure 2Tempus Aware programme identified eligible patients for BASECAMP-1. We partnered with Tempus, a third-party NGS provider, to identify patients with tumours that had HLA-A*02 LOH using a routine clinical diagnostic. With the patient-matching programme, Aware, when a patient with HLA-A*02 LOH is identified at a BASECAMP-1 study site, Tempus communicates with the site investigators that one of their patients might be eligible for BASECAMP-1. HLA, human leucocyte antigen; LOH, loss of heterozygosity; MD, medical doctor; NGS, next-generation sequencing; PI, principal investigator.Patient and public involvement The BASECAMP-1 study design, recruitment strategies and patient materials have been informed by ongoing consultations with patient advocacy groups and investigators who represent diverse patient communities.Results The first patient was enrolled on BASECAMP-1 in May 2022 using a traditional patient identification approach, operating at 13 study sites. The Tempus Aware programme began patient identification in March 2023 and ran concurrently at 9 of these study sites. As of 5 April 2025, a total of 85 participants with tumour-associated HLA-A*02 LOH had enrolled on BASECAMP-1 ( table 1; figure 3). The baseline demographics (gender, age, race and tumour types) for the enrolled populations in the two groups were similar.Table 1Patients consented, screened and enrolled on BASECAMP-1 using two approachesTraditional identification of patients by study investigatorsBioinformatic identification of patients using Tempus AwareLength of enrolment period, months4230Clinical trial sites with a patient with tumour-associated HLA-A*02 LOH enrolled by the screening method, n7*8*Patients who consented for BASECAMP-1 screening, n191867†Patients who enrolled on BASECAMP-1 who have tumour-associated HLA-A*02 LOH and met other study eligibility criteria, n (%)30 (1.5)55 (82)Median (range) screening time, days97 (46, 138)26 (14, 95)*Of the 13 sites, all participated in traditional patient identification, and 9 sites participated in the Tempus Aware programme.†Tempus identified 282 patients in its database who were germline heterozygous HLA-A*02 with LOH. Of these, 67 patients consented to be screened for BASECAMP-1. HLA, human leucocyte antigen; LOH, loss of heterozygosity.Figure 3BASECAMP-1 cumulative enrolment. Using a traditional screening approach over 42 months, 1918 patients at 13 study sites consented to be screened for the BASECAMP-1 study; of these, 30 consented participants had tumour-associated HLA-A*02 LOH and met other study eligibility criteria. Using the Aware programme over 30 months at 9 of these study sites, 282 patients were bioinformatically identified as potential candidates. Of the 67 patients who consented to be screened further, 55 had confirmed tumour-associated HLA-A*02 LOH and met other study eligibility criteria. Thus, the NGS algorithm was dramatically more efficient at identifying patients. HLA, human leucocyte antigen; LOH, loss of heterozygosity; NGS, next-generation sequencing.Using a traditional identification approach over 42 months, 1918 patients at 13 study sites consented to be screened for the study; of these, 30 (1.5%) consented participants had tumour-associated HLA-A*02 LOH and met other study eligibility criteria. That is, approximately 1 eligible patient enrolled per 64 screened, and approximately 0.7 patients enrolled per month. Based on internal BASECAMP-1 study data as of 5 April 2025, approximately 60% of traditionally identified patients were determined to be ineligible due to germline HLA type before NGS tumour testing was initiated. Patients still need to satisfy all enrolment criteria (figure 1) and have adequate tumour sample for analysis.Using the Aware programme over 30 months at 9 study sites, 282 patients were bioinformatically identified as potential candidates. Of the 67 patients who consented to be screened further, 55 (82%) had confirmed tumour-associated HLA-A*02 LOH and met other study eligibility criteria; that is, approximately 1.8 patients enrolled per month.Unrelated to the two screening approaches, an adjustment to the eligibility criteria was made in October 2023. Initial required HLA-A typing was restricted to patients with HLA-A*02:01. However, after defining the amino acids involved in Tmod interaction with HLA-A,14 we recognised that the Tmod blocker was active against all HLA-A*02 alleles. The HLA-A*02:01 allele is more prevalent in non-Hispanic White populations compared with other racial and ethnic populations, whereas the distribution of HLA-A*02 alleles is similar across race and ethnicity. Expanding eligibility criteria to include patients with all germline HLA-A*02 alleles led to 16% more Hispanic/Latino patients screened for HLA LOH, 43% more Black/African American, and 112% more Asian/Pacific Islander patients.15 16Discussion The BASECAMP-1 study was established to proactively identify patients who are germline HLA-A*02 heterozygous with tumour-associated HLA-A*02 LOH for treatment on an A2 Bio interventional trial and overcome the challenges of enrolling patients on precision oncology studies. A master screening study like BASECAMP-1 has several advantages for enrolling patients with specific genetic markers into CAR T clinical trials.First, this design mitigates the urgency to enrol in an interventional trial. Patients’ molecular characteristics can be interrogated while in remission or while undergoing other therapies, providing a queue of molecularly eligible patients who can enrol in therapeutic studies once clinically appropriate. Leukapheresis and collection of lymphocytes can be scheduled more conveniently for the patients and study site because HLA and LOH status is known well before the need to manufacture the cell therapy product. In addition, because the therapy can be manufactured on demand, there is more time to re-manufacture the therapeutic product, if needed. When applying this screening model in precision oncology clinical studies, the potential for temporal or spatial genomic heterogeneity must be considered when interpreting clinical data.Second, the leukapheresis product is collected and stored before participants receive additional lines of chemotherapy, resulting in potentially healthier cells for manufacturing that may lead to a more fit cell therapy product.17 In retrospective analyses, both T-cell fitness (eg, doubling time) and lower tumour burden (eg, earlier lines of therapy) have been associated with response and durable remissions.18–20Third, within BASECAMP-1, there is ongoing real-world data collection for patients with and without HLA LOH to allow further understanding of the natural history of patients with these tumours. This population can serve as a comparator arm in subsequent propensity analysis and has the potential to augment statistical power compared with a single-arm interventional trial.21 22 In addition, leveraging a single screening study for multiple interventional trials helps maximise resource utilisation and provides efficiency gains for both sites and sponsors.During the BASECAMP-1 study execution, we established a working academic/industry partnership with Tempus that enabled data mining of clinical NGS diagnostic tests at study sites to screen patients with appropriate molecular characteristics. This served as a more efficient method to identify patients with tumour-associated HLA-A*02 LOH, and this approach could be leveraged for other biomarker-driven therapies. These methods will become increasingly valuable as precision oncology trials continue to target more rare patient populations. Partnering with an NGS provider to identify patients for precision oncology has several advantages. These patients are identified using NGS results produced as part of the normal clinical workflow, dramatically reducing resource expenditure by study staff and accelerating patient accrual. The financial burden for sponsors is reduced because they do not have to screen as many patients who will ultimately not be eligible to move forward to interventional treatment. Site staff members can focus on more efficient confirmatory second-stage screening and scheduling of patients whose tumours are genetically eligible for the study and not expend staff resources on screen-failure patients. Patients can focus on studies or treatment options that best fit their disease, not further exhaust their time and tumour samples on studies with a low rate of eligibility.In addition, the Tempus xT assay used to determine tumour-associated HLA-A*02 LOH includes analysis for tumour purity, mutations in 648 genes and, when sufficient nucleic acids are available, RNA sequencing. This provides a large dataset in the BASECAMP-1 study for additional translational discovery.15 23 This approach is generalisable to other genomic targets; the bioinformatic screening described here is readily applicable to identifying patients with gene amplifications (copy number variants) or complex algorithmic signatures such as microsatellite instability and tumour mutational burden. Non-genomic biomarkers, such as specific protein expression levels typically measured by immunohistochemistry, would need to be incorporated into the clinico-genomic database to be used with this screening approach. Although the Aware programme requires that a Tempus test is ordered, similar partnerships can be used to ensure potentially eligible patients are identified agnostic of the testing platform used.The future of precision medicine will accelerate as biomarkers being studied in clinical trials can be integrated into panels used in routine pathology workflow and seamlessly transmitted into electronic medical records. This will shift the prescreening burden from ordering a separate, study-specific test to routine diagnostic workup, ensuring patients can access all potential treatment options available. Traditional screening of patients one at a time to identify rare patients with molecular characteristics for target therapy is time-intensive for study staff and costly to study budgets. Repetitive NGS testing depletes vital samples of patient tissue and results in additional unnecessary blood draws if this testing must be repeated for every sponsor-specific clinical trial. Leveraging higher-quality NGS results from routine clinical care is key to timely enrolment, cost efficiencies and ensuring patient accessibility.This experience also highlights the utility of carefully evaluating inclusion criteria in precision oncology trials. By including participants with additional HLA-A*02 alleles, enrolment has increased generally and, specifically, increased within minority populations where HLA-A*02:01 is underrepresented: 16% more Hispanic/Latino, 43% more Black/African American and 112% more Asian/Pacific Islander patients were identified through this expansion.One limitation of this analysis is that the two screening methods used in the BASECAMP-1 study operated concurrently for the final 30 months of the reporting period at the nine sites participating in the Aware programme. The bioinformatic algorithm might have identified eligible patients before they could be captured by standard screening; therefore, the concurrent use of the Aware programme may have reduced the apparent yield of the traditional approach at these sites. Additionally, while bioinformatic screening identified a large pool of potential candidates (n=282), only a subset (n=67) proceeded to consent. This attrition reflects the distinction between a molecular match and a viable clinical candidate. Reasons for non-enrolment included medical ineligibility, the retrospective nature of some database hits (where patients had since died or were lost to follow-up), physician discretion (eg, patients stable on current therapy or with poor performance status), and patient refusal.Many of the challenges related to patient identification, cost, time and resource burden, as well as a need to maximise benefit while minimising burden for patients, have recently been highlighted by the Society for Immunotherapy of Cancer with a call to action to adapt clinical trial design for development of immunotherapies.24 25 The BASECAMP-1 study provides an example of a novel clinical trial design that can overcome challenges with patient identification for precision oncology trials and underscores the importance of innovative collaborations for accelerating development of novel CAR T therapies.