Cancer Clinical Trials Research Articles

Photodynamic therapy with redaporfin activated by pulsed laser light

SignificanceRedaporfin is a photosensitizer under clinical trials for head and neck cancer. In previous work, a continuous light source was used in several tumor models, either in vitro or in vivo. However, the use of pulsed light (PL) sources can bring advantages to photodynamic therapy, such as higher penetration depths. ApproachTo study the influence of the light source in the efficacy of redaporfin-PDT, balb/c mice were inoculated with subcutaneous CT26 tumors. Redaporfin was activated using a PL source at 750 nm, with a repetition rate of 20 Hz and an energy per pulse of 24 mJ/cm2. Illumination time ranged from 5 to 15 min. ResultsThe results show an acute inflammatory response followed by a fast shrinkage and necrosis of the tumors and no significant side effects. ConclusionsThe activation of redaporfin with PL leads to good response of the tumors and further studies are being held to optimize the treatment conditions.

104 Exploring Stakeholder Perspectives Regarding the Barriers and Enablers to UK-Based Clinical Trials for Lung Cancer

104 Exploring Stakeholder Perspectives Regarding the Barriers and Enablers to UK-Based Clinical Trials for Lung Cancer

Toward Equitable Precision Oncology: Monitoring Racial and Ethnic Inclusion in Genomics and Clinical Trials.

Ethnic diversity in cancer research is crucial as race/ethnicity influences cancer incidence, survival, drug response, molecular pathways, and epigenetic phenomena. In 2018, we began a project to examine racial/ethnic diversity in cancer research, with a commitment to review these disparities every 4 years. This report is our second assessment, detailing the present state of racial/ethnic diversity in cancer genomics and clinical trials. To study racial/ethnic inclusion in cancer genomics, we extracted ethnic records from all data sets available at cBioPortal (n = 125,128 patients) and cancer-related genome-wide association studies (n = 28,011,282 patients) between 2018 and 2022. Concerning clinical trials, we selected studies related to breast cancer (n = 125,518 patients, 181 studies), lung cancer (n = 34,329 patients, 119 studies), and colorectal cancer (n = 40,808 patients, 105 studies). In cancer genomics (N = 28,136,410), 3% of individuals lack racial/ethnic registries; tumor samples were collected predominantly from White patients (89.14%), followed by Asian (7%), African American (0.55%), and Hispanic (0.21%) patients and other populations (0.1%). In clinical trials (N = 200,655), data on race/ethnicity are missing for 60.14% of the participants; for individuals whose race/ethnicity was recorded, most were characterized as White (28.33%), followed by Asian (7.64%), African (1.79), other ethnicities (1.37), and Hispanic (0.73). Racial/ethnic representation significantly deviates from global ethnic proportions (P ≤ .001) across all data sets, with White patients outnumbering other ethnic groups by a factor of approximately 4-6. Our second update on racial/ethnic representation in cancer research highlights the persistent overrepresentation of White populations in cancer genomics and a notable absence of racial/ethnic information across clinical trials. To ensure more equitable and effective precision oncology, future efforts should address the reasons behind the insufficient representation of ethnically diverse populations in cancer research.

Cancer in general practice research priorities in Australia.

The Primary Care Collaborative Cancer Clinical Trials Group (PC4) is funded by Cancer Australia to support the development of new cancer in primary care research. We undertook a research prioritisation exercise to identify cancer research priorities in Australian general practice. We adapted the nominal group technique, including a literature search and stakeholder survey. An expert group from the Primary Care Collaborative Cancer Clinical Trials Group consolidated and ranked priorities. A second stakeholder survey reviewing the top 50 priorities informed a final prioritisation workshop. Overall, 311 priorities were identified across the cancer continuum. Nearly one-third of priorities were related to cancer survivorship and included strategies to detect recurrence, behavioural interventions and tools to assess physical and psychosocial aspects of survivorship. Prevention/early detection comprised 43.4% of priorities. Palliative care produced the least priorities (9.6%). Cross cutting research priorities (15.1%) included quality and models of care. This is the first study to identify cancer research priorities for general practice in Australia. It could be used to inform the development of targeted research and funding to improve the care and outcomes for Australians affected by cancer.

Survival trends for left and right sided colon cancer using population-based SEER database: A forty-five-year analysis from 1975 to 2019.

Survival differences between left-sided colon cancer (LSCC) and right-sided colon cancer (RSCC) has been previously reported with mixed results, with various study periods not accounting for other causes of mortality. We sought to assess the trends in colon cancer cause- specific survival (CSS) and overall survival (OS) based on sidedness. Fine-Gray competing risk and Cox models were used to analyze Surveillance, Epidemiology, and End Results (SEER) population-based cohort from 1975 to 2019. Various interval periods were identified based on the timeline of clinical adoption of modern chemotherapy (1975-1989, interval period A; 1990-2004, B; and 2005-2019, C). Of the 227,637 patients, 50.1% were female and 46.2% were RSCC. RSCC was more common for African Americans (51.5%), older patients (age ≥65; 51.4%), females (50.4%), while LSCC was more common among Whites (53.1%; p < 0.001), younger patients (age 18-49, 64.6%; 50-64, 62.3%; p < 0.001), males (58.1%; p < 0.001). The Median CSS for LSCC and RCC were 19.3 and 16.7 years respectively for interval period A (1975-1989). Median CSS for interval periods B and C were not reached (more than half of the cohort was still living at the end of the follow-up period). Adjusted CSS was superior for LSCC versus RSCC for the most recent interval period C (HR 0.89; 0.86-0.92; p < 0.001). LSCC consistently showed superior OS for all study periods. Stage stratification showed worse CSS for localized and regional LSCC in the earlier study periods, but the risk attenuated over time. However, left sided distant disease had superior CSS per stage for all interval periods. OS was better for LSCC irrespective of stage, with gradual improvement over time. LSCC was associated with superior survival compared to right sided tumors. With the adoption of modern chemotherapy regimens, prognosis between LSCC and RSCC became more divergent in favor of LSCC. Colon cancer clinical trials should strongly consider tumor sidedness as an enrollment factor.

MRNA vaccines in cancer clinical trials: HPV16 tumor-derived antigens (e6 and e7 oncoproteins) associated with head and neck squamous cell carcinoma (HNSCC), oropharyngeal and cervical cancers

Human papillomavirus (HPV) induces the most common sexually transmitted disease and has been classified in the Alphapapillomavirus genus, Papillomaviridae family. They are non‒enveloped viruses presenting a closed circular double‒stranded non‒segmented DNA genome of approximately 8 kb that infect the anogenital epithelium causing cervical cancer, anal and penis cancer. There are viral groups based on their oncogenic activity as high‒risk types, low‒risk types and types of undetermined‒risk. mRNA vaccines are being evaluated in people with HPV-related cancers. This study described how mRNA cancer vaccines work and their applications recruiting several strategies for HPV cancer immunotherapy. Several biopharmaceuticals are developing mRNA vaccines encoding neoepitopes that can induce immune responses against target tumors. One trial is testing a personalized mRNA vaccine in combination with an immune checkpoint inhibitor in patients with advanced head and neck cancer. The production of therapeutic mRNA proteins for development of vaccine cancer have been manufactured by upstream and downstream methods. Several stages are processed in bioreactors using input and output parameters to measure the quality control of purified substance. Thus, novel technologies using different mRNA delivery system can be able to be integrated in clinical trials of HPV16 tumor-derived antigens associated cervical intraepithelial lesions of different stages until head and neck squamous cell carcinoma, oropharyngeal and cervical cancers.

Socioeconomic Deprivation and Health Care Use in Patients Enrolled in SWOG Cancer Clinical Trials

Reducing acute care use is an important strategy for improving value. Patients with cancer are at risk for unplanned emergency department (ED) visits and hospital stays (HS). Clinical trial patients have homogeneous treatment; despite this, structural barriers to care may independently impact acute care use. To examine whether ED visits and HS within 12 months of trial enrollment are more common among Medicare enrollees who live in areas of socioeconomic deprivation or have Medicaid insurance. This cohort study included patients with cancer who were 65 years or older and treated in SWOG Cancer Research Network trials from 1999 to 2018 using data linked to Medicare claims. Data were collected from 1999 to 2019 and analyzed from 2022 to 2024. Outcomes were ED visits, HS, and costs in the first year following enrollment. Neighborhood socioeconomic deprivation was measured using patients' zip code linked to the Area Deprivation Index (ADI), measured on a 0 to 100 scale for increasing deprivation and categorized into tertiles (T1 to T3). Type of insurance was classified as Medicare with or without commercial insurance vs dual Medicare and Medicaid. Demographic, clinical, and prognostic factors were captured from trial records. Multivariable regression was used, and the association of ADI and insurance with each outcome was considered separately. In total, 3027 trial participants were analyzed. The median (range) age was 71 (65-98) years, 1280 (32.3%) were female, 221 (7.3%) were Black patients, 2717 (89.8%) were White patients, 90 (3.0%) had Medicare and Medicaid insurance, and 660 (22.3%) were in the areas of highest deprivation (ADI-T3). In all, 1094 patients (36.1%) had an ED visit and 983 patients (32.4%) had an HS. In multivariable generalized estimating equation, patients living in areas categorized as ADI-T3 were more likely to have an ED visit (OR, 1.34; 95% CI, 1.10-1.62; P = .004). A similar but nonsignificant pattern was observed for HS (OR, 1.36; 95% CI, 0.96-1.93; P = .08). Patients from areas with the highest deprivation had a 62% increase in risk of either an ED visit or HS (OR, 1.62; 95% CI, 1.25-2.09; P < .001). Patients with Medicare and Medicaid were 96% more likely to have an ED visit (OR, 1.96; 95% CI, 1.56-2.46; P < .001). In this cohort of older patients enrolled in clinical trials, neighborhood deprivation and economic disadvantage were associated with an increase in ED visits and HS. Efforts are needed to ensure adequate resources to prevent unplanned use of acute care in socioeconomically vulnerable populations.

Impact of Broadening Trial Eligibility Criteria on the Inclusion of Patients With Brain Metastases in Cancer Clinical Trials: Time Series Analyses for 2012-2022.

In October 2017, an ASCO, Friends of Cancer Research (FoCR), and US Food and Drug Administration (ASCO/FoCR/FDA) task force recommended that common eligibility criteria be modified to make trials more inclusive. We examined whether patterns of exclusions regarding patients with brain metastases changed over time in relation to these recommendations. Trial eligibility criteria were abstracted from ClinicalTrials.gov for phase I-III US-based interventional clinical trials for patients with advanced breast, colorectal, lung, or melanoma cancers from January 2012 to December 2022. Trials were examined to determine whether patients with brain metastases were not excluded, conditionally excluded (ie, excluded in some circumstances), or wholly excluded. An interrupted time series analysis with multinomial logistic regression was used to determine whether the ASCO/FoCR/FDA recommendations were associated with changes in brain metastases criteria. We evaluated N = 3,077 trials. Patients with brain metastases were not excluded in 506 trials (16.4%), conditionally excluded in 2,263 trials (73.5%), and wholly excluded in 308 trials (10.0%). In the postrecommendation period, we estimated a 68% increase in the odds of brain metastases not excluded compared with conditionally excluded (odds ratio, 1.68 [95% CI, 1.06 to 2.66], P = .03). The proportion of trials in which patients with brain metastases were not excluded increased (from 11.5% v 17.3%) and conditionally excluded decreased (from 82.3% to 75.2%, P = .03). We found no difference in the proportion of trials in which patients with brain metastases were wholly excluded (7.5% v 6.2%, P = .42). The ASCO/FoCR/FDA task force recommendations were associated with a shift in patterns of brain metastases exclusion criteria from conditionally excluded to not excluded. These findings demonstrate that the cancer clinical trial community has begun to change the way trials are written to be more inclusive.

Overview of Molecular Diagnostics in Irish Clinical Oncology

Background Molecular diagnostics are critical for informing cancer patient care. In Ireland, the National Cancer Control Programme (NCCP) develops cancer therapy regimens, which include relevant information on molecular indications. Here, we present a collated overview of the current molecular indications of all NCCP systemic anti-cancer therapy regimens and the funding statuses of their associated drugs. Furthermore, we also provide estimates for the scale of required molecular testing in cancer therapy and for the clinical genetic sequencing capacity of Ireland, and provide a summary of current cancer clinical trials in Ireland which have molecular components. Methods Through a combination of web scraping, keyword search, and manual review, we performed a full review of all 757 indications included in the 476 therapy regimens published to date by the NCCP to identify therapy indications with explicit molecular criteria. For all cancer types identified in these indications, we obtained incidence rates in Ireland from National Cancer Registry Ireland to predict the number of patients yearly who stand to benefit from a molecular test. We then applied molecular subtype rates from published literature to estimate the number of patients who would then qualify for a relevant molecularly guided therapy. Results We identified 210 indications for 148 NCCP therapy regimens that include molecular criteria. These 210 molecular indications encompassed 85 genetic criteria, 137 cellular biomarker criteria, 57 molecularly informed drugs, and over 20 cancer types. We estimated that up to approximately 50% of cancer patients in Ireland could qualify for a molecular test and that the majority of tested patients would qualify for a treatment informed by a molecular test. Conclusions As personalised cancer medicine continues to develop in Ireland, this study will provide a baseline understanding of current practices. We anticipate that work such as this will help to inform planning in the healthcare system.

Broadening Eligibility Criteria and Diversity among Patients for Cancer Clinical Trials

BackgroundCertain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown.MethodsUsing a nationwide electronic health record–derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria.ResultsWhen applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49 years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34).ConclusionsData-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.)

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.

Utilizing Adeno-Associated Virus Vectors for Advancing Cancer Gene Therapy

Adeno-associated virus (AAV) has proven highly effective as a delivery vector in clinical trials for gene therapy. The safety and efficacy of AAV have led to its application as a novel approach for cancer treatment. Many successful clinical trials of cancer have demonstrated the feasibility of this approach. This review mainly introduces the structure, characteristics and application of AAV in tumor models. The promise of gene therapy in addressing diverse diseases has become evident, with AAV vectors playing a pivotal role in its achievements. AAV's exceptional safety profile and efficacy in gene therapy have spurred their application as a novel approach in the realm of cancer treatment. Clinical trials in this area have yielded impressive results, underlining the potential of AAV in combating cancer. This review provides a comprehensive insight into AAV's structural attributes and unique characteristics, emphasizing their significance in the context of tumor models. AAV's ability to efficiently deliver therapeutic genes to cancer cells, coupled with minimal risk, marks a significant breakthrough in oncology.

Abstract 1008: Pilot evaluation of an online course for primary care providers on preparing patients for cancer discussions with their oncologists

Abstract Introduction: Cancer clinical trial (CCT) accrual is only 5-8%, and barriers to participate can be more acute for underserved groups. Enrollment of racial/ethnic minorities, older adults, adolescents, and young adults is not adequate to understand treatment outcomes unique to these populations. Education before seeing an oncologist can increase patients’ willingness to ask and consider receiving treatment through a CCT. Because primary care providers (PCPs) interact with patients during diagnosis, provide ongoing care, and are a trusted source of information, they can educate and normalize inquiries about therapeutic CCTs. The aim of this study was to pilot test an innovative, tailored online CCT course for PCPs. Methods: To participate, PCPs (MD, DO, NP, or PA) had to provide care in an outpatient setting, refer patients to a cancer treatment specialist in the past year, and be an English speaker residing in the U.S. or its territories. PCPs were recruited from Clinical Directors Network, University of Pennsylvania, and University of Florida. The 1-hour online course includes four modules hosted by a PCP and radiation oncologist with video segments of a CCT expert who summarized CCT recruitment research. Participants interact with patient scenarios and learn about the patient’s cancer diagnosis and medical/personal background. Videos of actors playing the roles of patient and doctor demonstrate communication skills taught in the course. PCPs completed short surveys prior to and immediately after completing the course. Results: 28 PCPs participated. PCPs were mainly MDs (88.9%), residents (17, 60.7%), White (46.4%), non-Hispanic/Latino (92.9%), and 50% women. Mean knowledge of CCTs scores (0-100%) increased significantly from pre (M=56.7, SD=17.5) to post (M=82.1, SD=12; p&amp;lt;.001) indicating that PCPs answered more true/false statements about CCTs correctly after training. Using a 1-5 scale with 5=strongly agree, PCPs’ attitudes and beliefs scores also increased significantly from pre (M=4.2, SD=.6) to post (4.7, SD=.4, p&amp;lt;.001) indicating that PCPs were more likely to agree they have a role in their patients’ cancer treatment, including CCTs, after training. Using the same scale, PCPs’ willingness to communicate about CCTs increased significantly from pre (M=4.4, SD= .5) to post (M=4.7, SD=.5, p=.007), indicating that PCPs were more willing to engage with patients diagnosed with cancer before referring them to a cancer specialist after training. Conclusions: Significant pilot findings in knowledge, attitudes and beliefs, and communication scores demonstrate that the online course was effective at educating PCPs about CCTs, and improving PCPs’ attitudes about the CCT referral process, and their willingness to engage in their patients’ cancer care. Future research will include a larger sample and explore the course’s impact on PCP’s referral behavior. Citation Format: Alyssa Crowe, Elisa S. Weiss, Margo Michaels, Domenic Durante, Maria Sae-Hau, Andrea Cassells, Carla L. Fisher, Jason Arnold, Taylor Vasquez, Ana Natale-Pereira, Raymond Mailhot, Zhongyue Zhang, Carma L. Bylund. Pilot evaluation of an online course for primary care providers on preparing patients for cancer discussions with their oncologists [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1008.

Abstract 4825: Addressing financial toxicity in cancer clinical trial participation: Barriers and facilitators of enrolling in a reimbursement program for out-of-pocket travel costs

Abstract Financial toxicity has been associated with adverse outcomes for patients with cancer. Out-of-pocket (OOP) costs contribute to the high financial toxicity (FT) experienced by patients with cancer. Cancer clinical trial (CCT) participants face significant extra OOP expenses presenting a barrier to participation and retention. To address FT in CCTs, the Lazarex Foundation created the Improving Patient Access to Cancer Clinical Trials (IMPACT) Program, a financial reimbursement program (FRP) for OOP travel and lodging costs associated with therapeutic CCT participation. Our study aimed to quantify the FT experienced by patients in CCTs and understand their experience to determine the barriers and facilitators of enrolling in the Lazarex IMPACT Program. Patients enrolled in a CCT were referred to the IMPACT team to determine eligibility. Patients were eligible for IMPACT if they were active on a therapeutic CCT and their household income was less than 700% of the most recent HHS federal poverty guidelines. Patients who enrolled in the program were invited to participate in a brief semi-structured interview via telephone call. We used grounded theory techniques of analysis to identify themes of barriers and facilitators to enrollment in the Lazarex IMPACT program at our cancer center. Table 1 shows the emerging themes from the interviews as barriers and facilitators of enrolling in IMPACT. As a part of the interview process, patients also completed the COST-FACIT questionnaire, a patent reported outcomes measure to evaluate the degree of FT associated with cancer. COST scores in our cohort (n=39) ranged from 14-39.6, mean=27.12, median=27.5; SD=7.96. Following enrollment in the program, patients on average had COST scores indicating low degrees of financial distress. Taken altogether, our results have the potential to inform the development of FRPs for patients with cancer to facilitate their participation in CCTs. Table 1. Emerging themes from grounded analysis of semi-structured interviews and their frequency Barrier to enrolling in FRP program. No. of Participants Facilitator of enrolling in FRP program No. of Participants Patients wanted to be made aware of program earlier in their CCT timeline 4 Enrollment process was easy and straightforward 17 Patients made aware of program after their CCT started 3 IMPACT team contacted patients to offer program 13 CCT Team unaware of program availability 3 Patients learned about the program through their CCT team 8 Patients reported difficulty with technology access and literacy 3 Patients reported sufficient technology access and literacy 4 Patients reported hesitancy sharing financial information 2 Cancer foundation was timely and helpful in enrollment process 2 Patients reported difficulty navigating vast resources at cancer center 1 Cancer Center social workers provided connection to program 1 Citation Format: Elizabeth Ramos, Vivian Nguyen, Ashley Santaniello, Dana Dornsife, Robert G. Johnson, Paul E. Wileyto, Robert H. Vonderheide, Carmen E. Guerra. Addressing financial toxicity in cancer clinical trial participation: Barriers and facilitators of enrolling in a reimbursement program for out-of-pocket travel costs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4825.

Abstract 1002: The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials

Abstract The National Comprehensive Cancer Center Network cancer guidelines state that the best management for a cancer patient is on a clinical trial. However, the demographics of 74 registration trials for oral cancer therapies from 2009 - 2019 show only 2.5% of participating patients were Black. Similarly, of the 3,593 patients enrolled in all registration trials for new cancer drugs approved by the FDA in 2019, only 4% were Black patients. A third analysis showed that between 2008 and 2018, only 3.1% of cancer trial patients were Black. The underrepresentation of Black patients in cancer clinical trials is a complex issue that requires a multifaceted solution. Complicated, interdependent causes include, but are not limited to system, provider, and patient bias. Increasing globalization of clinical trials also contributes to a widening gap in Black patient enrollment. Achieving diversity among clinical trial participants requires intention in study design regarding accrual sites and outreach, and involvement of a diverse trial workforce. The ideal clinical trial system would minimize system, provider, and patient biases. Such a system already exists in the Historically Black Colleges and Universities (HBCU) system. HBCUs represent 3% of institutions of higher education in the USA, yet they enroll 16% of Black students and confer 24% of all baccalaureate degrees earned by Black students. 40% of Black engineers, 50% of Black lawyers, 70% of Black physicians, and a staggering 80% of Black judges attended an HBCU. HBCUs are exceptional at impacting communities of Color and have been doing so for centuries. The HBCU Cancer Trials Consortium (HBCU CTC) is a network of HBCUs and Ally institutions that aims to bring innovative cancer clinical trials to historically underserved communities and honor the legacy of HBCUs, which have consistently and successfully served underserved communities for over a century. The HBCU CTC will oversee and conduct cancer clinical trials at member institutions. We envision founding flagship members to include HBCUs that provide graduate medical education and training, such as Howard, Meharry, Charles Drew, and Morehouse. Non-HBCUs committed to the mission are invited to join the consortium as Ally institutions (eg. MSIs). Membership is not exclusive of membership in other cancer consortia. The HBCU CTC will provide shared resource services for member institutions that lack expertise or funding to conduct services locally (eg. data management, DSMB, biostatistics, a cancer focused IRB, central radiology, and central pathology). The Consortium will also work to develop local infrastructure support for the conduct of cancer clinical trials at member institutions. Citation Format: Sheldon L. Holder, Robert A. Winn, Wafik S. El-Deiry. The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1002.

Abstract 4824: Multi-level intervention to increase minority cancer patient enrollment to clinical treatment trials- Study design considerations and baseline characteristics from the ACTWONDER2S Study

Abstract Introduction: Black/African American (AA) and Hispanic cancer patients are underrepresented in cancer clinical trials (CCTs). Disparities stem from multiple factors, thus, comprehensive, multi-level interventions (MLI) are needed. Presented here is a conceptual framework for selecting the appropriate study design for MLIs using ACTWONDER2S, a multi-level intervention (MLI) aimed to increase Black/AA and Hispanic patient participation into CCTs, as an illustrative example. Baseline characteristics of the ACTWONDER2S target populations are also provided. Methods: ACTWONDER2S integrates community health educator and digital tools into an MLI targeting community residents and physicians in the Moffitt Cancer Center (MCC) catchment area, as well as MCC patients, physicians and CCT coordinators. A literature review of the relative strengths and weakness of 5 candidate designs for MLIs was conducted, and a cluster stratified randomized design was selected. Geospatial analytics were used to identify clusters of census tracts (“priority zones”) with high Black/AA and Hispanic populations for intervention deployment. Baseline characteristics of the priority zones were described using US Census data and other sources. Results: 14 priority zones were identified, which were matched on population characteristics and randomized into intervention (n=7) and control (n=7) zones. There were no statistically significant differences between the intervention and control priority zones in total population size (paired t-test p-value=0.63), proportions of Black/AA (p=0.133) and Hispanic populations p=0.17), and distance (in miles) from MCC (p=0.64). Approximately 35.8% and 16.5% of the intervention priority zones were Hispanic or Black/AA, respectively. Average distance to MCC, cancer cases, referral and CCT enrollment rates were also similar between groups. Conclusion: Decision frameworks for MLI study design selection are lacking. The framework provided here for ACTWONDER2S can be applied to other studies seeking to evaluate MLIs. Furthermore, the randomization of the priority zones produced optimal target populations for testing the efficacy of the MIL within ACTWONDER2S. Citation Format: Dana E. Rollison, Rossybelle P. Amorrortu, Lindsay N. Fuzzell, Melany A. Garcia, Elliott S. Tapia-Kwan, Yayi Zhao, Steven A. Eschrich, Bob R. Gore, Brian S. Mittman, Nathanael B. Stanley, Susan T. Vadaparampil. Multi-level intervention to increase minority cancer patient enrollment to clinical treatment trials- Study design considerations and baseline characteristics from the ACTWONDER2S Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4824.

Abstract 2386: Meta-analysis of efficacy and safety in early-phase clinical trials for refractory colorectal cancer

Abstract Introduction: Despite a decade of metastatic colorectal cancer (mCRC) therapeutic innovations, a comprehensive synthesis of patient outcome and risk-benefit assessment of phase 1/2 trials, extending beyond single-center studies, is missing. The aim of this meta-analysis is to assess efficacy, safety, and trends over time for phase 1 and 2 mCRC trials by examining clinical benefit rate (CBR), overall response rate (ORR), grade 3 or higher adverse events (AE), and discontinuation due to AE. Methods: The protocol and search were preregistered on PROSPERO. We searched PubMed and Embase for publications of phase 1/2 trials between 2010-2022. Reports were screened for inclusion criteria, followed by data-extraction by two researchers. Trials reporting on non-standard therapies for treatment-refractory mCRC or trials reporting specific mCRC efficacy data were included. CBR was defined as the proportion of patients with complete/partial response or stable disease ≥14 weeks. We used logit transformations for pooled effect analysis via a random-effects model, assigning study weights by the inverse variance method. Subgroup analyses were performed for publication year, preselection on molecular traits, and drug class: antiangiogenics, chemotherapy, immunomodulator, targeted therapy, or vaccine. Data are presented with 95% confidence intervals (CI); reported differences had non-overlapping CIs. Results: The search strategy yielded 4175 unique reports, from which we extracted data for 279 trials. Most trials were phase 1 (63%). ORR was limited to 6% [6-7] in both phase 1 and 2, CBR was higher in phase 2 than in phase 1 trials (36% vs 27%). Trials testing antiangiogenic drugs had the highest CBR (47%) and immunomodulators the highest ORR (8%). Trials with patients preselected on molecular traits had higher CBR compared to other trials (38% vs 28%). We observed an increase in efficacy, especially in phase 2 trials, with a CBR rising from 22% to 42% between trials published in 2010-2012 and 2019-2021. Compared with 2010-2012, trials in 2019-2021 were more often testing immunomodulators (23% vs 4%), performed on molecular preselected populations (38% vs 4%), and including younger patients (median age &amp;lt;60 in 66% vs 44%). The occurrence of grade 3+ AE was 33% [28-38] in both phase 1 and 2. AE led to discontinuation in 12% of phase 1 trial patients, and 7% of phase 2 patients. Grade 3+ AE occurred in 4% of vaccine trial patients, in contrast to 41% in trials on targeted therapies. Occurrence of grade 3+ AE did not change over time. Conclusion: We found limited ORR and CBR in early phase trials conducted in 2010-2021 for mCRC patients, while noting severe AEs in many patients. However, during this period, clinical benefit rate increased for phase 2 trials, possibly due to evolving study strategies that entail testing new treatment types in a younger, fitter, and stricter preselected study population based on molecular traits. Citation Format: Maarten A. Huismans, Lidwien P. Smabers, Niels N. van Nieuwenhuijzen, Monique C. Minnema, Miriam Koopman, Hugo J. Snippert, Anne M. May, Jeanine M. Roodhart. Meta-analysis of efficacy and safety in early-phase clinical trials for refractory colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2386.

Abstract 3638: Pathologic endpoints as surrogates for survival endpoints in neoadjuvant immunotherapy clinical trials for non-small cell lung cancer

Abstract Background: The use of neoadjuvant immunotherapy alone or in combination has rapidly evolved in the last 5 years. There is significant debate as to whether pathologic complete response (pCR) or major pathologic response (MPR) can be considered a surrogate endpoint for survival. We therefore performed a systematic review and meta-analysis to evaluate the surrogacy of pCR and MPR for event free survival (EFS) in neoadjuvant clinical trials for early-stage NSCLC. Methods: We performed a systematic literature search on PubMed and reviewed abstracts of the most relevant international conferences until June 2023. Relevant information relative to response rates, Odds Ratios (ORs) of response, 2-years EFS rates and Hazard ratios (HRs) were retrieved from all eligible clinical trials and the association were analyzed. To evaluate patients level surrogacy the association between response rate and 2-year EFS was evaluated. In trials presenting EFS rates by achievement of pCR and MPR a forest plot with random effect model was also produced. For trial level surrogacy, ORs for pCR and MPR and HRs for EFS were retrieved and analyzed using a linear regression model weighted by sample size. R2 and linear regression slope were used respectively to estimate the proportion of variation in EFS effect explained by pCR effect and the magnitude of change in EFS effect as a function of the magnitude of change in pCR effect. The R2 with 95% CI were calculated by bootstrapping approach. Results: Seven RCTs were identified for a total of 2940 patients. At patient level, the R2 of pCR and MPR with 2-years EFS were 0.82 (0.66-0.94) and 0.81 (0.63-0.93), respectively, with slopes of 0.96 (0.68-1.19) and 0.64 (0.45-0.85), respectively. At trial level, R2 for association of OR for response and HR for EFS was 0.58 (0.00-0.97) and 0.61 (0.00-0.97) for pCR and MPR, respectively. Conclusions: While we were able to show a strong correlation between pCR and EFS, trial level surrogacy was not proven. The lack of surrogacy can be related to the high heterogeneity among clinical trials and the still scarce number of data available. More research to reduce the heterogeneity (e.g., pathological evaluation, surgery, and staging harmonization) must be done to introduce pCR as a primary measure to predict EFS. Citation Format: Robert B. Cameron, Jacobi B. Hines, Alessandra Esposito, Christine Bestvina, Marina C. Garassino, Valter Torri, Rajat Thawani. Pathologic endpoints as surrogates for survival endpoints in neoadjuvant immunotherapy clinical trials for non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3638.

Abstract 6789: Development of an in vitro gastric cancer 3D co-culture platform using a microphysiological system (MPS) to improve outcomes in oncology clinical trials

Abstract Introduction: Despite significant advancements in scientific and diagnostic technologies, clinical trials for cancer often fail due to a lack of efficacy. Access to a platform that accurately predicts patient response is crucial to increase the success rate of clinical studies, and to minimize unnecessary exposure to ineffective and potentially harmful drug testing for patients. Because of the complexity of the disease, it would be beneficial to deploy patient samples for drug testing in a side-by-side comparison during the clinical trial. An accurate prediction of patient response earlier in the clinical study would aid decision making to determine the appropriate duration of treatment for each patient. Methods: We developed a 3D human cell co-culture model using our proprietary MPS technology, the Curio-spheroid Curiochip. Using patient samples isolated and expanded from either ascites fluids or biopsies to recapitulate the clinical phenotypes of advanced gastric cancer, we quantified the migratory properties of the patient cancer cells (i.e., the unique metastatic potential), and measured the level of secretion of VEGF. Somatic mutational analyses using NGS and RNAseq were performed for subtyping and clustering the samples. The patient cancer cells were expanded within 2 weeks post-collection, and used to form a spheroid that was loaded into a hydrogel embedded within the Curio-Spheroid, enabling the patient spheroids to interact through the hydrogel with neighboring (healthy) human endothelial cells. The patient spheroids induced aggressive vasculogenesis in the co-culture model, which was subdued by the anti-VEGFR2 antibody Ramucirumab. The platform was retrospectively validated with the Standard-of-Care (SOC) treatments that the patients received. Results: The patient cell testing took 3-4 weeks from sample collection to imaging. The patient cells preserved their migratory capacity, pro-angiogenic potential and drug responses in the vascularized model. The dose responses to SOC in the platform were consistent with the actual patient response assessments based on RECIST criteria, supporting the potential to use this platform to accurately predict patient clinical responses. Conclusions: The Curio-spheroid 3D co-culture model of vascularized gastric cancer provides a dynamic microenvironment to preserve the phenotypes of the patient cells and cell-cell interactions that are known to influence drug responses. This platform is compatible with high-throughput screening (HTS) for target or drug discovery with a good assay window. The ability to accurately recapitulate patient responses to SOC in the clinic make the Curio-Spheroid platform a promising method to test patient samples and measure drug responses of patients in real time during ongoing clinical trials. Citation Format: Yeongmin Choi, Sumin Kim, Youngsook Song, Yangji Kim, Jin Hawn Jang, Suryong Kim, Jihye Baek, Delaney Donnelly, Bushra Rajiput, Byungjun Lee, Woo Sun Kwon, Tsung-Li Liu, Kyusuk Baek, Sanghee Yoo, Sun Young Rha. Development of an in vitro gastric cancer 3D co-culture platform using a microphysiological system (MPS) to improve outcomes in oncology clinical trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6789.

Abstract 3900: A high-throughput platform identifies novel drug combinations towards acute myeloid leukemia therapy

Abstract Molecularly targeted therapies have reshaped oncology in recent decades, though not all patients are eligible for such treatments and resistance mechanisms limit clinical benefit. In response, combination therapies, which can induce potent synthetic lethalities, bypass drug resistance, and expand treatment options, are increasingly being developed. A major hurdle limiting novel combination therapy discovery is the sheer combinatorics associated with broadly testing two or more agents. Thus, there is a practical need for methodologies that prioritize test compounds and technologies for rapid and efficient screening. Towards these ends, we have developed a novel combination drug screening workflow that integrates machine learning-based drug synergy predictions with a high throughput droplet microfluidics-based screening platform. Our physical system, or FlowMatrix, consists of 9,216 nano wells arrayed in a 96 × 96 grid in which cells are incubated and drug compounds delivered via emulsified droplets along both its rows and columns to facilitate combination screening. Following multi-day incubation, live cells are imaged with fluorescence microscopy and drug combination synergies are calculated from cellular viabilities. In our current setup, which includes four dose drug treatments with replicates and controls, we capture complete data (control, single agent, and 4 × 4 drug-drug combination viability measurements) for up to 100 unique drug combinations within the 9,216 dual droplet loaded wells of one FlowMatrix. Our to-date screening efforts have focused on acute myeloid leukemia (AML) specifically, where we have profiled 12,700 AML cell line-drug combinations in our system. This encompasses &amp;gt;3,700 unique drug combinations profiled in 7 distinct AML cell lines with 183 total matrix runs. Among the strongest hits observed in our screens and confirmed with validation studies (~65% confirmation rate) are combinations currently being tested in clinical trials for other cancers and established therapies paired with non-cancer indicated drugs. In particular, we are interrogating combinations involving CDK12 inhibitors, which affect the transcription of DNA repair proteins, splicing, and cancer cell progression, including unexpected partner drugs that potentiate the effects of CDK12 blockade in AML cell lines. We have uncovered additional unexpected synergistic combinations with KIT inhibitors in RUNX1-RUNX1T1 altered AML lines, ATR inhibitors (including an established combination with Gemcitabine), and the BCL-2 inhibitor Venetoclax, including known partnerships with chemotherapies (e.g. Decitabine and Daunorubicin) and other targeted inhibitors. Deeper studies are underway to further validate and characterize these candidates towards expanding treatment options for AML. Ultimately, our platform may radically enhance drug combination screening potential. Citation Format: Anthony R. Soltis, Boryana Zhelyazkova, Pascal Drane, Efstathios Eleftheriadis, Andrew Ventresco, David A. Weitz, Arlinda Lee, Anthony J. Iafrate. A high-throughput platform identifies novel drug combinations towards acute myeloid leukemia therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3900.