Early Phase Cancer Clinical Trials Research Articles

Abstract B123: Multilevel influences on Black and Hispanic/Latine patient participation in early phase cancer clinical trials

Abstract Black and Hispanic/Latine patients are disproportionately burdened by cancer yet underrepresented in cancer clinical trials. Diverse participation in cancer clinical trials is essential to identify potential group differences in risks and benefits and to ensure equitable access to cutting-edge therapeutics. Prior research has focused on barriers to representation in later phase trials with less focus on early phase cancer clinical trials (EPCCTs). EPCCTs may include unique barriers to representation based on safety focus and intensive monitoring. We investigate multi-level influences on EPCCT participation for Black and Hispanic/Latine patients through in-depth qualitative interviews with (n=30) Black or Hispanic/Latine metastatic cancer patients and (n=30) oncology providers/staff from two community practices. Using the Ecological Model as a guiding framework, we explored facilitators and barriers to diverse EPCCT participation at the patient level, provider level, health system/policy level, and community level. We utilized Rapid Qualitative Inquiry to gain pragmatic, accurate understanding. At the patient level, we identified informational (e.g., understanding of cancer), emotional (e.g., trust), and instrumental (e.g., transportation) influences on Black and Hispanic/Latine participation. The most pervasive barrier to EPCCT inclusion was lack of invitation for Black and Hispanic/Latine patients. At the provider/staff level, key barriers to representation included low EPCCT knowledge among providers, preconceptions about barriers for Black and Hispanic/Latine patients, and perceived loss of control/relationship with patients/caregivers. At the health system/policy level, critical barriers included insufficient time to discuss EPCCTs, concerns about impact of trials on systems (e.g., wait-time for scans), and provider discomfort with referral process (sending patients to Phase I team without specific trial knowledge). At the community level, salient influences on patient decision-making were identified (e.g., peers, youtube). We conducted a systemwide survey of (n=81) oncology providers and their attitudes, beliefs, and behaviors regarding EPCCTs; we determined how attitudes and beliefs related to EPCCT referral behaviors. We have planned interventions to mitigate each barrier and leverage each facilitator to increase representation. It is critical to identify and address relevant local barriers to ensure equitable access to novel therapeutics and generalizability of scientific discoveries. Citation Format: Jessica Lewis, Amy Smoyer, Erin Singleton, Marcella Nunez-Smith, Imran Saeed, Patricia LoRusso. Multilevel influences on Black and Hispanic/Latine patient participation in early phase cancer clinical trials [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B123.

Hospital Factors Influencing the Mobility of Patients for Systemic Therapies in Breast and Bowel Cancer in the Metastatic Setting: A National Population-based Evaluation

AimsThis national study investigated hospital quality and patient factors associated with treatment location for systemic anticancer treatment (SACT) in patients with metastatic cancers. Materials and methodsUsing linked administrative datasets from the English NHS, we identified all patients diagnosed with metastatic breast and bowel cancer between 1 January 2016 and 31 December 2018, who subsequently received SACT within 4 months from diagnosis. The extent to which patients bypassed their nearest hospital was investigated using a geographic information system (ArcGIS). Conditional logistic regression models were used to estimate the impact of travel time, hospital quality and patient characteristics on where patients underwent SACT. Results541 of 2,364 women (22.9%) diagnosed with metastatic breast cancer, and 2,809 of 10,050 (28.0%) patients diagnosed with metastatic bowel cancer bypassed their nearest hospital providing SACT. There was a strong preference for receiving treatment at hospitals near where patients lived (p < 0.001). However, patients who were younger (p = 0.043 for breast cancer; p < 0.001 for bowel cancer) or from rural areas (p = 0.001 for breast cancer; p < 0.001 for bowel cancer) were more likely to travel to more distant hospitals. Patients diagnosed with rectal cancer were more likely to travel further for SACT than patients with colon cancer (p = 0.002). Patients were more likely to travel to comprehensive cancer centres (p = 0.019 for bowel cancer) and designated Experimental Cancer Medicine Centres (ECMCs) although the latter association was not significant. Patients were less likely to receive SACT in hospitals with the highest readmission rates (p = 0.046 for bowel cancer). ConclusionPatients with metastatic cancer receiving primary SACT are prepared to travel to alternative more distant hospitals for treatment with a preference for larger comprehensive centres providing multimodal care or hospitals which offer early phase cancer clinical trials.

Decision-making and autonomy among participants in early-phase cancer immunotherapy trials: a qualitative study

BackgroundParticipants considering early-phase cancer clinical trials (CTs) need to understand the unique risks and benefits prior to providing informed consent. This qualitative study explored the factors that influence patients’ decisions about participating in early-phase cancer immunotherapy CTs through the ethical lens of relational autonomy.MethodsUsing an interpretive descriptive design, interviews were conducted with 21 adult patients with advanced cancer who had enrolled in an early-phase CT. Data was analyzed using relational autonomy ethical theory and constant comparative analysis.ResultsThe extent to which participants perceived themselves as having a choice to participate in early-phase cancer immunotherapy CTs was a central construct. Perceptions of choice varied according to whether participants characterized their experience as an act of desperation or as an opportunity to receive a novel treatment. Intersecting psychosocial and structural factors influenced participants’ decision making about participating in early-phase cancer immunotherapy trials. These relational factors included: (1) being provided with hope; (2) having trust; (3) having the ability to withdraw; and (4) timing constraints.ConclusionsFindings highlight the continuum of perceived choice that exists among patients with cancer when considering participation in early-phase cancer immunotherapy CTs. All participants were interpreted as exhibiting some degree of relational autonomy within the psychosocial and structural context of early-phase CT decision making. This study offers insights into the intersection of cancer care delivery, personal beliefs and values, and established CT processes and structures that can inform future practices and policies associated with early-phase cancer immunotherapy CTs to better support patients in making informed decisions.

Abstract LB_A14: Factors associated with enrollment, participation, and survival of patients on early phase cancer clinical trials

Abstract Background: Enrollment and participation of a diverse patient (pt) population for early phase clinical trials is crucial for determining the safety and efficacy of new cancer therapies. However, strict eligibility criteria, co-occurring conditions, and socioeconomic barriers can limit pt participation. Improving methods of pt recruitment, enrollment, and support while on clinical trials has the potential to accelerate trial accrual and diversity within trial cohorts. Methods: We conducted a retrospective chart review of oncology pts seen by the Early Phase Clinic Trials Unit (EPTU) at the Mount Sinai Hospital between July 2018 and October 2022. Pts had advanced solid tumors and had already received standard of care treatment. Data including demographics, cancer diagnosis, clinical trial enrollment, and overall survival (OS) were obtained from the electronic medical record. Demographic and clinical differences were compared between patients who enrolled on an early phase trial (T) and those who did not (NT). Univariable logistic regression was used to determine predictors of successful trial enrollment. Univariable Cox proportional hazards models were conducted to analyze factors associated with survival time on trial treating death of any cause as the outcome and censoring pts lost to follow-up or alive at trial termination. Results: 261 referrals were evaluated representing 234 unique patients. Of these, 60 pts (25.64%) enrolled in a clinical trial. No significant differences were found between T and NT pts in gender, race, ethnicity, language, or insurance status. In univariable logistic regression, number of previous systemic therapies was inversely associated with likelihood of going on trial (OR 0.87 95% CI [0.75, 1.00] p= 0.045). Pts with skin cancer had a higher likelihood of going on trial compared to those with other tumor types (OR 4.57 95% CI [1.27, 18.4] p=0.021). Of T patients, 27 (45.00%) were White, 8 (13.33%) were Black, 9 (15.00%) were Asian, and 12 (20.00%) were Hispanic; 12 (20.00%) did not speak English. The median time between initial appointment and Day 1 on trial was 0.67 months. Median length of time on trial was 2.07 months, and median OS from enrollment was 4.16 months (IQR [2.21, 8.16]). In univariable Cox regression, an ECOG PS of 1 compared to 0 was associated with increased risk of death (HR 1.91 95% CI [1.01, 3.61] p=0.050). Both Spanish speaking and all non-English speaking T pts had an increased risk of death compared to English speaking T pts (HR 5.09 95% CI [2.00, 12.19]; HR 2.34 95% CI [1.04, 5.25]). Conclusion: There were no significant demographic barriers to trial enrollment. However, times on trial and overall survival were modest, with the latter associated with poorer performance status. Given their increased risk of death, more support is needed for non-English speaking patients who participate on early phase trials. Citation Format: Elena Baldwin, Grace Van Hyfte, Natalie Lucas, Kathy Wu, Gary Shelton, Suzan Aird, Grace Chung, Gabriela Fazilov, Lisa Fitzgerald, Olivia Hapanowicz, Khadijah Holley, Paula King, Ashley Lu, Nathasha Melukkaran, Miriam San Lucas, Issamar Urena, Aleksandra Wawrzyniak, Marshall Posner, Matthew D Galsky, Thomas U Marron, Deborah B Doroshow. Factors associated with enrollment, participation, and survival of patients on early phase cancer clinical trials [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A14.

Time toxicity associated with early phase clinical trial participation

Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n= 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Timing of receipt of palliative care among participants in early-phase cancer clinical trials.

260 Background: Early phase clinical trials (EP-CTs) investigate novel therapeutics for patients with cancer. EP-CT participants often have advanced stages of disease, have received multiple lines of prior therapies, and remain sufficiently functional to enroll on EP-CTs. Limited research exists to describe the use and timing of palliative care (PC) in EP-CTs. Methods: We conducted a prospective study of patients with cancer enrolled on EP-CTs at Massachusetts General Hospital from April 2021- January 2023. We extracted demographic and clinical characteristics from the electronic health record as well as timing of receipt of PC (before/during EP-CT vs after EP-CT/never) and reason for PC referral documented in the referral. We used patient-reported surveys at time of treatment initiation to assess symptom burden (Edmonton Symptom Assessment System [ESAS]), financial toxicity (Comprehensive Score for Financial Toxicity [COST], lower scores indicate greater toxicity), quality of life (QOL; Functional Assessment of Cancer Therapy-General [FACT-G]), and hope (Herth Hope Index [HHI], higher scores indicate greater hope). We used descriptive statistics to explore associations of timing of receipt of PC with patient characteristics, symptom burden, financial wellbeing, QOL, and hope. Results: Of 221 eligible patients, we enrolled 204 (enrollment rate 92.3%, median age=63.4 years [range 54.8-70.2]; 57.0% female, 94.1% metastatic cancer). Less than one third of patients received PC before/during EP-CT (31.8% before/during, 68.2% post/never). Reasons for referral include: symptom management (84.4%), coping (12.5%), advance care planning (7.8%), illness understanding (1.6%), and treatment decision-making (1.6%). Patients age &lt;65 were more likely than those 65+ to receive PC before/during EP-CT (39.1% vs 22.1%, p=0.01). Patients with ECOG=1 were more likely than those with ECOG=0 to receive PC before/during EP-CT enrollment than post enrollment/never (37.9% vs 22.9%, p=0.01). Patients who received PC before/during EP-CT had a higher symptom burden (ESAS: 20.7 vs 15.5, p=0.01), lower QOL (70.9 vs 77.0, p=0.003), and worse financial toxicity (25.2 vs 29.4, p=0.003). We found no significant differences in hope scores based on timing of receipt of PC (27.6 vs 27.1, p=0.53). Conclusions: In this prospective cohort of EP-CT participants with cancer,less than one third received PC before/during EP-CT enrollment. Symptom management was the most common reason for referral to PC, which aligns with our patient-reported survey data. Characteristics associated with receiving PC before/during trial participation include age, decreased performance status, higher symptom burden, lower QOL, and increased financial toxicity. These findings suggest that earlier PC was appropriately delivered to those most in need yet highlight the importance of efforts to ensure earlier integration of PC in this population.

Racial differences in longitudinal toxicities of anticancer agents in early phase cancer clinical trials.

Racial differences have been reported in toxicity outcomes for anticancer drug treatments. However, these observations were often from studies with small sample sizes, and many only reported the maximum grade of toxicity and no longitudinal information. This current analysis aims to investigate racial differences in longitudinal toxicities using a large-scale clinical trials database. Early-phase clinical trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute, USA, that evaluated cytotoxic drugs and molecularly targeted agents between March 2000 and December 2012 were studied. Race was categorized as White, Black or African-American, and Asian. Each toxicity's grade prevalence, mean grade at each cycle, and time to develop grade 2 or higher toxicity was evaluated. In total, 25,442 patients from 697 trials were included in this study. The number of patients categorized as White, Black, and Asian designations was 22,756 (89%), 1874 (7%), and 812 (3%), respectively. Notable findings include the rate of any grade of diarrhea in Black people was 26% and 21% lower than that of White and Asian people. The median time to the first grade 2 or higher event was 6 cycles in White people, 8 in Black people, and 6 in Asian people. The rate of any grade hyperglycemia was significantly higher in Asian people. Although we identified several racial differences in longitudinal toxicities, most were of generally lower grade. Further study is needed to clarify the cause of racial differences in treatment-associated toxicities.

Modeling synergism in early phase cancer trials with drug combination with continuous dose levels: is there an added value?

In parametric Bayesian designs of early phase cancer clinical trials with drug combinations exploring a discrete set of partially ordered doses, several authors claimed that there is no added value in including an interaction term to model synergism between the two drugs. In this paper, we investigate these claims in the setting of continuous dose levels of the two agents. Parametric models will be used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity and efficacy. Trial design proceeds by treating cohorts of two patients simultaneously receiving different dose combinations and response adaptive randomization. We compare trial safety and efficiency of the estimated maximum tolerated dose (MTD) curve between models that include an interaction term with models without the synergism parameter with extensive simulations. Under a selected class of dose-toxicity models and dose escalation algorithm, we found that not including an interaction term in the model can compromise the safety of the trial and reduce the pointwise reliability of the estimated MTD curve.

384P Concordance of genomic alterations in tumour tissue and ctDNA in patients with colorectal cancer referred for early phase trials

Plasma-based circulating tumour DNA (ctDNA) provides a minimally invasive, contemporaneous assessment of genomic alterations (GAs) and captures tumour heterogeneity. We compare GAs identified in ctDNA and archival tissue in patients (pts) with metastatic colorectal cancer (CRC) recruited to the Tumour Characterisation to Guide Experimental Targeted Therapy (TARGET) trial, aiming to match pts to early-phase cancer clinical trials (EPCCT). Archival tumour tissue was analysed using next generation sequencing (NGS) panels (24 genes), and plasma-based ctDNA was analysed using a local research NGS panel (641 genes). Results were discussed in a molecular tumour board (MTB) to define actionability. Factors associated with the likelihood of having additional GAs in ctDNA were explored using logistic regression analysis and odds ratio (OR). 101 pts with CRC were recruited to TARGET. The median age was 56 years and 61% were male. Pts had NGS testing panels from primary (70%) or metastatic (30%) archival tumour tissue. The median age of archival tissue tested was 25 months (range 0-117 months) and 98% of pts received active treatment in the intervening time. Tissue and ctDNA NGS identified clinically relevant GAs in 90% and 79% of pts respectively, with a median of 2 GAs per pt. The most common GAs in ctDNA were TP53 (53%), KRAS (47%), APC (44%), and PIK3CA (12%). There was poor concordance of identified GAs between tissue and ctDNA (agreement=66.3%, Cohen's k<0, p=0.91). 23% of pts had clinically relevant GAs in ctDNA that were not identified in tissue, the commonest being KRAS (29%). There was no association between the presence of additional GAs in ctDNA with number of treatment lines (OR:1.23, p= 0.32), age of archival tissue (OR: 1.01, p= 0.91) or primary vs. metastatic archival tissue site (OR: 0.34, p= 0.11). The presence of liver metastases was associated with a higher likelihood of concordance between tissue and ctDNA NGS (OR: 3.5, p= 0.03). Overall, ctDNA-derived GAs were considered actionable in 51% of pts. Of those, 28% were a potential match for an EPCCT. Plasma-based ctDNA can be used as a contemporaneous tool to identify actionable GAs and guide treatment options for pts with metastatic CRC.

Decision-making about clinical trial options among older patients with metastatic cancer who have exhausted standard therapies

ObjectivesOlder adults under-enroll in early phase cancer clinical trials. There are limited data on their trial experiences, which hampers our ability to understand potential reasons and responses to under-enrollment. We aimed to explore older adults' experiences and deliberations with phase 1 trials. Materials and MethodsWe analyzed 101 in-depth interviews with 39 adults (average 2.6 interviews per participant) about their experiences with phase 1 trials. All respondents were ≥ 65 years and had advanced cancer. Interviews lasted 60–90 min and were audio-recorded, transcribed, and analyzed to identify respondents' understanding of clinical research, perceptions of early phase trials, and experiences with enrollment. ResultsClinical trial participation was an interactive process that unfolded over time. Older adults relied on ongoing guidance and discussion with their oncologist to navigate the process. Respondents were generally interested in life-prolonging therapies, including enrollment in early phase clinical trials, but did not necessarily state this explicitly to their oncologist. While respondents did not mention age as a limitation to trials participation, participants age > 70 were less enthusiastic about participation and more often discussed their quality of life and weighed benefits of trial participation in the context of their remaining months of life. ConclusionEarly phase clinical trial enrollment is complex, and older adults rely on their oncologist to navigate this process. Acknowledging this complexity through shared decision-making may ensure that older adults have appropriate opportunities to enroll in early phase clinical trials and guard against inappropriate under-enrollment.

Differential response rates in early-phase cancer clinical trials (EPCCT).

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for &gt;6 mos and 7% for &gt;12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response &gt;6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response &gt; 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p&lt;0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

Optimal biological dose: a systematic review in cancer phase I clinical trials

BackgroundClassical phase 1 dose-finding designs based on a single toxicity endpoint to assess the maximum tolerated dose were initially developed in the context of cytotoxic drugs. With the emergence of molecular targeted agents and immunotherapies, the concept of optimal biological dose (OBD) was subsequently introduced to account for efficacy in addition to toxicity. The objective was therefore to provide an overview of published phase 1 cancer clinical trials relying on the concept of OBD.MethodsWe performed a systematic review through a computerized search of the MEDLINE database to identify early phase cancer clinical trials that relied on OBD. Relevant publications were selected based on a two-step process by two independent readers. Relevant information (phase, type of therapeutic agents, objectives, endpoints and dose-finding design) were collected.ResultsWe retrieved 37 articles. OBD was clearly mentioned as a trial objective (primary or secondary) for 22 articles and was traditionally defined as the smallest dose maximizing an efficacy criterion such as biological target: biological response, immune cells count for immunotherapies, or biological cell count for targeted therapies. Most trials considered a binary toxicity endpoint defined in terms of the proportion of patients who experienced a dose-limiting toxicity. Only two articles relied on an adaptive dose escalation design.ConclusionsIn practice, OBD should be a primary objective for the assessment of the recommended phase 2 dose (RP2D) for a targeted therapy or immunotherapy phase I cancer trial. Dose escalation designs have to be adapted accordingly to account for both efficacy and toxicity.

Research Related Tumour Biopsies in Early-Phase Trials with Simultaneous Molecular Characterisation – a Single Unit Experience

Early-phase cancer clinical trials are becoming increasingly accessible for patients with advanced cancer who have exhausted standard treatment options and later phase trial options. Many of these trials mandate research tissue biopsies. Research biopsies have been perceived as ethically fraught due to the perception of potential coercion of vulnerable human subjects. We performed an audit of two years of practice to assess the safety of ultrasound (US)-guided research biopsies, and to look at the yield of a simultaneous tumour next-generation sequencing (NGS) and immunohistochemistry (IHC) molecular characterisation programme. We show that in our institution, US-guided research biopsies were safe, produced adequate tumour content and in a selected subset who underwent in-house NGS sequencing, showed a high rate of actionable mutations with 30% having a Tier 1 variant. Nevertheless, these research biopsies may only provide direct benefit for a minority of patients and we conclude with a reflection on the importance of obtaining truly informed consent.

Palliative care referrals in patients with advanced cancer on early-phase cancer clinical trials (EP-CTs).

29 Background: EP-CTs investigate novel therapeutic approaches for patients with cancer, but little is known about the utilization of supportive care services, specifically palliative care (PC), in this population. Methods: We conducted a retrospective review of consecutive patients enrolled on EP-CTs at the MGH Cancer Center from 2017-2019. Sociodemographic and clinical variables, including utilization of PC services, were obtained via chart review. Details of the PC evaluation were compared between patients who received first referral to PC while enrolled on an EP-CT versus those who received a PC referral at any point after diagnosis. Results: Among 426 patients enrolled on EP-CTs (median age 63 years; 44% male), 249 (59%) received a PC referral at any time following a diagnosis of cancer (median age 57 years, 58% male). Eighty-six (35%) were referred prior to enrollment on EP-CT, 44 (18%) were referred while on EP-CT, and 119 (48%) were referred post-EP-CT. Patients referred on EP-CT were younger (median 56 vs 63 years, p &lt; 0.0001) than those enrolled on EP-CTs. For patients referred while on EP-CT, 48% had a PC consult within 30 days of enrollment (range: 0-530 days); median number of PC visits was 3 (range: 0-37); median time from first PC consult to death or termination of EP-CT was 32 days (range: 1-213). Of 44 patients referred on EP-CT, 2 (5%) died while on EP-CT. Of the remaining patients, median time from first PC consult to date of death was 79 days (IQR: 45-178 days). Most common reasons for referral included pain (22, 50%), non-pain symptoms (21, 48%), and goals of care/advanced care planning (20, 45%). Of these referrals, 13 (30%) were initiated as inpatients versus 31 (70%) as outpatients. Pain was most commonly cited for outpatient referral (35%), followed by non-pain symptoms (25%) and goals of care (23%). Non-pain symptoms (40%) and goals of care (36%) were most commonly cited reasons for inpatient referral, followed by pain (24%). Of referrals while on EP-CT, 23 (52%) were made by EP-CT staff, including MD and APP, 7 (16%) from the primary oncologist, and 1 (2%) was self-referral. 26 (57%) of patients referred to PC during trial were also referred to hospice, with a median time from last PC consult to hospice referral of 24 days (range: -2-322). Conclusions: A majority of patients with advanced cancer enrolled on EP-CTs received a PC referral. The timeline and method of referral varied, but most patients did not receive a referral until or following enrollment on an EP-CT. Future work will focus on developing a standard referral protocol for patients enrolled on EP-CTs.

Impact of COVID-19 in paediatric early-phase cancer clinical trials in Europe: A report from the Innovative Therapies for Children with Cancer (ITCC) consortium.

IntroductionData regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I–II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC).MethodsA survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020.ResultsThirty-one of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared with that in 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. In addition, 26% of sites had restrictions on performing trial assessments because of local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organisational and structural changes.ConclusionThe study reveals a profound disruption of paediatric cancer early-phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises.

Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress.

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy.

Generation of Tumor Cells Expressing Firefly Luciferase (fLuc) to Evaluate the Effectiveness of CAR in a Murine Model.

Immunotherapy has been showed as a promisor treatment, in special for hematological diseases. Chimeric antigen receptor T cells (CARs) which are showing satisfactory results in early-phase cancer clinical trials can be highlighted. However, preclinical models are critical steps prior to clinical trial. In this way, a well-established preclinical model is an important key in order to confirm the proof of principle. For this purpose, in this chapter will be pointed the methods to generate tumor cells expressing firefly Luciferase. In turn, these modified cells will be used to create a subcutaneous and a systemic murine model of Burkitt's lymphoma in order to evaluate the effectiveness of CAR-T.

A multidisciplinary-tailored digital solution to data capture in early phase clinical trials.

2 Background: Data capture in early phase cancer clinical trials (EPCCT) is usually via paper records with manual transcription to the sponsor’s case report form. Capturing real time trial data directly to computer (eSource) may reduce errors and increase completeness and timeliness of data entry. A simulated system pilot took place between Oct 2018 and Jan 2019 at an EPCCT facility to appraise Foundry Health’s eSource system “ClinSpark”. Aims were to assess consistency and effectiveness of creating electronic templates for source data capture and live data collection compliance. Methods: A multidisciplinary focus group (MFG) (2 research nurses, 1 doctor, 3 data managers) was created to collaborate with Foundry Health staff. Specialised features of the eSource system were adapted to handle the complex needs of EPCCT. The pilot incorporated a 5 day boot camp for familiarisation to the digital platform; a conference room test using simulated patient data; construction of a trial template including contingency planning; and a clinic floor test with live simulated patient data collection using digital tablets. The MFG agreed on a 52 item user acceptance test listing ideal features for a data collection tool, with items classified as high, medium or low priority. Results: During the 3 month pilot, templates for 2 EPCCT were planned and created by the MFG. Using eSource, 43 items (83%) of the acceptance test were passed compared with 27 items (52%) for the current (paper) system. For the 30 high-priority items, eSource passed 30 (100%) compared with 22 for the paper system (73%). The paper system was not superior to eSource for any items assessed. Time saving and potential error reduction were noted as additional benefits. Conclusions: This process demonstrates that a multidisciplinary approach can be used to successfully integrate a customised eSource system working with previously untrained staff. Improved performance across pre-specified domains and potential additional benefits were noted. As FDA encourages use of digital solutions in clinical trials, using eSource provides a potential solution for compliant and efficient data capture from protocol assessments at investigator sites and rapid data transfer to sponsors.

A multidisciplinary-guided digital solution to data capture in early-phase clinical trials.

e18063 Background: Data capture in early phase cancer clinical trials (EPCCT) is usually via paper records with manual transcription to the sponsor’s case report form. Capturing real time trial data directly to computer (eSource) may reduce errors and increase completeness and timeliness of data entry. A simulated system pilot took place between Oct 2018 and Jan 2019 at an EPCCT facility to appraise Foundry Health’s eSource system “ClinSpark”. Aims were to assess consistency and effectiveness of creating electronic templates for source data capture and live data collection compliance. Methods: A multidisciplinary focus group (2 research nurses, 1 doctor, 3 data managers) was created to collaborate with Foundry Health staff. The focus group agreed on a 52 item user acceptance test listing ideal features for a data collection tool, classifying items as high, medium or low priority. Specialised features of the eSource system were adapted to handle the complex needs of EPCCT. The pilot incorporated a 5 day boot camp for familiarisation to the digital platform; a conference room test using simulated patient data; construction of a trial template including contingency planning; and a clinic floor test with live simulated patient data collection using digital tablets. Results: During the 3 month pilot, templates for 2 EPCCT were planned and created. Using eSource, 43 items (83%) of the acceptance test were passed compared with 27 items (52%) for the current (paper-based) system. The paper system did not pass any of the 9 items for which eSource failed. For the 30 high priority items, eSource passed 30 (100%) compared with 22 for the paper system (73%). Time saving and potential error reduction were noted as additional benefits. Conclusions: This process demonstrates that a multidisciplinary approach can be used to successfully integrate a customised eSource system working with previously untrained staff. Improved performance across pre-specified domains and potential additional benefits were noted. As FDA encourages the use of digital solutions in clinical trials, using eSource provides a potential solution for compliant and efficient capture of data from protocol assessments at investigator sites and rapid data transfer to sponsors.

Abstract 4559: KY-B602, a humanized anti-human OX40 antibody, enhances CD4+T cell activation and inhibits tumor growth in a syngeneic model

Abstract OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is mainly expressed on activated T cells. As a secondary costimulatory molecule, activated OX40 can increase effector T-cell survival, proliferation, and memory. Anti-OX40 monoclonal antibodies have shown anti-tumor efficacy. Recent preclinical studies further support the potential synergistic effects of agonist OX40 immunotherapy in combination with cancer vaccination or in sequential co-administration with PD1 antibody to revert PD1 resistance. Several anti-OX40 agonistic monoclonal antibodies are currently tested in early phase cancer clinical trials either in monotherapy or in combination with other immune modulators. KY-B602 is a novel humanized IgG1 anti-OX40 antibody under pre-clinical development. It was generated from hybridoma and humanized by CDR grafting and structure simulation. KY-B602 specifically binds to the extracellular domain of human OX40 with high affinity (KD = 5.1 nM, determined by Biacore). FACS study showed KY-B602 also binds to both human and cynomolgus monkey OX40 over-expressed on 293T cells (EC50 =4.6nM, EC50=6.1nM, respectively). Another, in HT1080 cell reporter assay, KY-B602 significantly increased IL-8 secretion through OX40 pathway. In addition, KY-B602 dose-dependently augmented IL-2 and IFN-gamma secretion from CD4+T cells, that were pre-stimulated with IL-2 and PHA. However, in FACS competition assay, KY-B602 did not affect OX40L binding to OX40, suggesting that KY-B602 binds to a different epitope with that of OX40L. Moreover, KY-B602 inhibits in vivo tumor growth in MC38 syngeneic model. In summary, the current data of KY-B602 support its potency for cancer therapy. Citation Format: feng hao, feng he, mingxuan ning, zhaoshuai bai, jinying ning. KY-B602, a humanized anti-human OX40 antibody, enhances CD4+T cell activation and inhibits tumor growth in a syngeneic model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4559.