PURPOSE:The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP). METHODS:Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon's two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety. RESULTS:Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs. CONCLUSION:Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.

Abstract Background: Few effective treatment options for advanced NSCLC are available following frontline immune checkpoint inhibitor (ICI)-based therapy. The randomized, phase II Lung-MAP S1800A study of RP versus SOC for pts with NSCLC previously treated with ICI demonstrated benefit in overall survival (OS) with an improved toxicity profile over SOC. SWOG S2302 Pragmatica-Lung was pragmatically designed to evaluate OS while increasing representation in trial participation. The interim analysis was previously reported. Methods: S2302 is a registration-intent randomized phase III trial for pts with advanced NSCLC who previously received ICI for at least 84 days and platinum-based therapy, randomized to SOC or RP, stratified by immediate prior therapy including ICI (yes/no) and PS (0/1 v. 2). The pragmatic design led to eligibility focused on stage, prior therapy and safety. Laboratory assessment and imaging were not required. The primary objective was OS. The secondary objectives were to compare OS between the arms within key subgroups, including squamous cell carcinoma (SCC) and to summarize reports of serious and unexpected high-grade treatment-related AEs. The accrual goal was 800 based on 90% power for an HR of 0.77 using a 1-sided 2.5% level log-rank test. Full information was 616 OS events. Results: S2302 enrolled 838 pts with 419 in each arm from March 2023 to December 2024. Study data were released at an interim analysis for futility. Median age (range) was 68 (34-88), 22% non-white /13% Black, 15% rural, 29% SCC, 63% adenocarcinoma, 81% had ICI as the most recent treatment, 13% had PS2. With 582 deaths reported, OS was not different between the arms (HR 1.04 [0.88-1.22] p= 0.66; median OS (mOS) was 10.1 months (mos) for RP and 10.0 mos for SOC). In SCC, the HR (95% CI) was 0.90 [0.66-1.22] p= 0.25 with mOS of 10.7 mos for RP and 9.6 mos with SOC. In nonSCC, the HR (95% CI) was 1.10 [0.91-1.34] p= 0.84 with mOS of 9.8 mos for RP and 10.6 mos with SOC. Conclusions: The pragmatic trial design led to rapid accrual with increased participant representativeness. RP did not improve OS overall but was not worse than SOC. Of note, for SCC, the estimated HR is < 1 and the confidence interval is consistent with non-inferiority bounds. We interpret that RP for SCC may provide an option equivalent to SOC with better tolerability. Support: NIH/NCI/NCTN grants U10CA180888 and U10CA180819; and in part by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eli Lilly and Company Citation Format: Karen L. Reckamp, Mary W. Redman, Konstantin H. Dragnev, Maya Khalil, Brian S. Henick, James Moon, Pasarlai Ahmadzai, Michael LeBlanc, Daniel R. Carrizosa, Paul J. Hesketh, Ellen V. Sigal, Jeff Allen, Andreas N. Saltos, Bryan A. Faller, Roy S. Herbst, Charles D. Blanke, Jhanelle E. Gray. Final Results from S2302—PRAGMATICA-LUNG: A prospective randomized study of ramucirumab plus pembrolizumab (RP) versus standard of care (SOC) for participants (pts) previously treated with immunotherapy for stage IV or recurrent non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT140.

LBA8505 Background: Savo, a highly selective MET -TKI, combined with osi, may overcome acquired MET -driven resistance in EGFRm advanced NSCLC after PD on EGFR-TKIs. Here we report primary results of the prespecified interim analysis (IA) in SACHI study, comparing efficacy and safety of savo + osi with chemo in this disease setting. Methods: In this randomized, open-label, phase 3 study, 250 EGFRm and MET amp advanced NSCLC patients (pts) post PD on first-line EGFR-TKI were planned ( MET copy number ≥5 or MET /CEP7 ratio of ≥2.0 by FISH for pts with prior 1 st /2 nd generation [G] EGFR-TKI; MET copy number ≥10 for pts with prior 3 rd G EGFR-TKI); T790M negative after PD on 1 st /2 nd G EGFR-TKI was required. Eligible pts were randomly assigned (1:1) to receive savo 400 or 600 mg QD (for body weight of < 50, or ≥ 50 kg respectively) + osi 80 mg QD, or chemo (pemetrexed + carboplatin/cisplatin), stratified by brain metastases, prior use of 3G EGFR-TKI, and type of EGFR mutations. Crossover to savo + osi after IRC-PD was permitted for chemo group. The primary endpoint, PFS by investigator (INV) per RECIST 1.1, was hierarchically tested via a stratified log-rank test in 3G EGFR-TKI treatment-naïve set firstly, then in ITT set. This is a prespecified IA conducted via an independent data monitoring committee to assess efficacy superiority or sample size re-estimation. Results: From 15 Oct 2021 to 30 Aug 2024 (DCO for IA), 211 pts were randomized to receive savo + osi or chemo (n=106 vs 105). Baseline characteristics were well balanced. mPFS by INV was significantly longer with savo + osi vs chemo in both 3G EGFR-TKI treatment-naïve set and ITT set ( p < 0.0001 in both sets), which met prespecified IA efficacy boundary ( p <0.0099 and 0.0228 in 2 sets, respectively); in 3G EGFR-TKI treated pts, mPFS was also significantly prolonged with savo + osi (6.9m vs 3.0m, HR=0.32, p < 0.0001). IRC-assessed PFS benefits were consistent (table). OS was immature at this DCO. Grade ≥3 TEAE occurred in 56.6% vs 57.3% of pts with savo + osi vs chemo; savo + osi had lower rates of hematologic events than chemo. Conclusion: Savo + osi significantly improved PFS versus chemo in MET amp NSCLC post EGFR-TKI, and the combination was safe and well tolerated. Savo + osi is a potential new treatment option for this genomically defined population. Clinical trial information: NCT05015608 . ITT set Savo + osiN=106 ChemoN=105 Hazard ratio/Odds ratio Two sided -p value mPFS (95% CI) (INV), m 8.2 (6.9, 11.2) 4.5 (3.0, 5.4) 0.34 <0.0001 mPFS (95% CI) (IRC), m 7.2 (5.7, 11.1) 4.2 (4.0, 5.7) 0.40 < 0.0001 ORR (95% CI) (IRC), % 63.2 (53.3, 72.4) 36.2 (27.0, 46.1) 3.05 < 0.0001 mDoR (95% CI) (IRC), m 9.7 (5.8, 12.4) 4.3 (2.8, 5.1) NA NA mOS (95%CI), m* 22.9 (16.8, NE) 17.7 (14.9, 26.3) 0.84 0.4191 *52.4% of pts in chemo group were crossover to receive savo + osi or other MET Inhibitors.

PURPOSE:Neuregulin-1 (NRG1) fusions are rare but actionable oncogenic drivers in solid tumors. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody. In this report, we present the antitumor activity and safety data of seribantumab from the CRESTONE study (ClinicalTrials.gov identifier: NCT04383210). PATIENTS AND METHODS:This was a prospective phase II clinical study in which patients with advanced solid tumors harboring an NRG1 fusion received seribantumab at a dose of 3,000 mg intravenously once weekly. The primary end point was objective response rate (ORR) by RECIST v1.1. Secondary end points included safety, duration of response, progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). The study was terminated before full enrollment because of sponsor decision, unrelated to safety or efficacy. RESULTS:A total of 54 patients with nine different tumor types featuring 19 different NRG1 fusion partners were enrolled. For the 29 patients included in the primary efficacy analysis, the investigator-assessed ORR was 34.5% (95% CI, 17.9 to 54.3), with a DCR of 79% (95% CI, 60 to 92). The median PFS was 5.4 (95% CI, 3.9 to 10.8) months; the median OS was 20.3 (95% CI, 10.2 to not reached) months. In patients with non-small cell lung cancer, eight of 22 achieved response (ORR, 36.4%). Adverse events (AEs) were mostly grade 1 or 2. The most common treatment-related AEs were diarrhea (39%), fatigue (32%), and nausea (22%). CONCLUSION:These results support the antitumor activity and safety of seribantumab in patients with advanced solid tumors harboring NRG1 fusions.

11016 Background: Effective therapy following frontline immune checkpoint inhibitor (ICI)-based treatment for advanced non-small cell lung cancer (NSCLC) is needed as limited options are available. Lung-MAP S1800A was a Phase II randomized study of ramucirumab plus pembrolizumab versus standard of care (SOC) for patients with NSCLC previously treated with immunotherapy that demonstrated benefit in overall survival (OS) with an improved toxicity profile over SOC. S2302 Pragmatica-Lung trial was pragmatically designed to evaluate the impact on OS while reducing barriers to participation and decreasing clinical trial staff burden. We assessed reduction in barriers to participation and clinical staff burden in S2302 in relationship to S1800A. Methods: S2302 (NCT05633602) is a registration-intent randomized phase III trial for patients with advanced NSCLC who previously received PD-(L)1 inhibitor therapy for at least 84 days and platinum-based therapy, stratified by immediate prior line of therapy including PD-(L)1 inhibition (yes/no) and PS (0/1 v. 2). The pragmatic design has limited eligibility criteria, which are focused on stage, prior therapy and safety to enroll patients as would occur in real world practice. Laboratory assessment and imaging with RECIST reads are not required due to the OS endpoint. Data collection was developed to minimize the burden with fewer time points for data submitted, number of forms and number of data elements. Concomitant medications are not collected. Given the known safety profile of both study drugs, only related and unexpected grade 3/4 and all grade 5 adverse events are collected. Results: Accrual to S2302 was robust with 838 patients enrolled from March 2023 to December 2024 (21 months), averaging > 50 patients/month in the final 6 months. The trial enrolled 77% White and 13% Black patients. versus 87% and 8%, respectively on S1800A. Over 65% were ≥ 65 years of age. Reduced data collection on S2302 relative to S1800A results in an estimated decrease in the number of forms and data elements submitted within the first year on study by 45% and 66%, respectively. Conclusions: Incorporating pragmatic elements into S2302 resulted in robust accrual, increased participant representativeness and access for patients. The reduced burden on staff due to decreased data forms and elements is substantial. Pragmatic design elements should be considered as we develop trials to generalize to a broad and representative population. Clinical trial information: NCT05633602 .

PURPOSE:Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and targetable genomic alterations. Two cohorts of patients with cyclin-dependent kinase inhibitor 2A (CDKN2A)-mutated tumors treated with palbociclib are reported: one with head and neck cancer (HNC) with both squamous and nonsquamous cell histologies, and one with histology-pooled (HP) cancers. METHODS:Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration. For the HNC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included OR, safety, progression-free survival, overall survival, duration of response, and duration of SD. RESULTS:Seventy patients with HNC (N = 28) or HP cancers (N = 42) were treated with palbociclib. For the HNC cohort, DC and OR rates were 40% (one-sided 90% CI, 27 to 100) and 4% (95% CI, <1 to 18), respectively. The null hypothesis was rejected (P = .002). For the HP cohort, DC and OR rates were 13% (one-sided 90% CI, 6 to 100) and 5% (95% CI, <1 to 17), respectively. The null hypothesis was not rejected. Thirty-one of 70 patients experienced treatment-related grade 3 to 4 adverse events (AEs) or serious AEs, the most common including neutropenia, thrombocytopenia, and leukopenia. CONCLUSION:Palbociclib met prespecified criteria to declare a signal of activity in patients with HNC with CDKN2A alterations, but not in the HP cohort.

8504 Background: In unselected patients (pts) with extensive-stage small cell lung cancer (ES-SCLC), the addition of immune checkpoint inhibitors (ICI) to chemotherapy resulted in a modest improvement in OS. In a retrospective analysis of a study with veliparib (PARP inhibitor [PARPi]) and temozolomide in patients with SCLC, Schlafen-11 (SLFN11) predicted PFS and OS benefit for the addition of PARPi. We evaluated whether the addition of PARPi (talazoparib) to standard-of-care maintenance ICI (atezolizumab) following frontline chemoimmunotherapy improved outcomes in pts with SLFN11-positive ES-SCLC. Methods: Participants with ES-SCLC expressing SLFN11 (H-score ≥ 1, evaluated centrally at MDACC) were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy and A. Randomization was stratified by Zebrod PS (0-1 vs 2) and use of consolidation thoracic radiation. The primary endpoint was PFS, and secondary endpoints included ORR, OS, and toxicity. The primary analysis was done using a 1-sided 10% level stratified log-rank test. Target sample size was 94 pts. Results: From June 2020 to December 2022, 309 pts were screened, of which 204 of 259 (79%) with evaluable tissue were SLFN11 positive, and 106 were randomized (52 A, 54 AT). Median follow up time is 5 months. Median age was 67 (45-84); 51 (48%) were females; 94 (89%) were white,102 (96%) were PS 0-1, and 26 (25%) had radiation prior to randomization. With 80 PFS events reported, PFS was significantly improved with AT (hazard ratio [80% CI]: 0.70 [0.52-0.94]; p = 0.056). Median PFS was 2.8 months (80% CI 2.0-2.9) for A and 4.2 months (80% CI 2.8-4.7) for AT. OS was not different (hazard ratio [80% CI]: 1.17 [0.80-1.71]; p = 0.30). Median OS was 8.5 months (80 % CI 7.4-12.7) for A and 9.4 months (80% CI 8.1-14.2) for AT. ORR was 16% (5/32, 80% CI 8-27%) for A and 12% (4/34, 80% CI 5-22%) for AT. Grade 3 or greater treatment related non-hematological adverse events (AEs) occurred in 13% pts in A and 15% in AT. Hematological AEs occurred 4% in A compared to 50% pts in AT (Expected for T) (p < 0.001). There were no treatment related grade 5 events. One participant on AT experienced grade 3 febrile neutropenia. The majority of grade 3 AEs were due to anemia (2% in A and 37% in AT). Only three pts discontinued treatment due to toxicity (2 in A and 1 in AT). Conclusions: This study met its primary endpoint demonstrating that maintenance AT improved PFS in SLFN11-selected patients with ES-SCLC. Hematologic toxicity was increased with AT as expected, with majority being grade 3 anemia. This study demonstrates the feasibility of conducting biomarker selected trials in SCLC, paving the way for future evaluation of novel therapies in selected SCLC populations. Clinical trial information: NCT04334941 .

PURPOSE To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC). METHODS Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients. RESULTS From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001). CONCLUSION Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.

OBJECTIVE:The Commission on Cancer (CoC) recently introduced a quality metric to optimize time between major head and neck surgery and adjuvant treatment (TAT) ≤6 weeks, as TAT delay adversely impacts patient survival. This study evaluates whether enhanced recovery after surgery (ERAS) for this population reduces the rate of postoperative complications, length of stay (LOS), and TAT. METHODS:Patients undergoing larynx or oral cavity resection with free flap reconstruction, ERAS, and adjuvant treatment after 2018 were compared to a historical pre-ERAS cohort. Patients underwent surgery at a single-institution tertiary referral center for complex head and neck oncology. Differences between groups were compared by chi-square, Fisher's exact, or Wilcoxon rank-sum test. TAT >6 weeks was evaluated with univariate and multivariable logistic regression. RESULTS:Thirty-nine pre-ERAS patients were compared to 39 ERAS patients. No demographic differences existed between groups. LOS was improved with ERAS (p = 0.005). ERAS patients were discharged to home and returned to their activities of daily living (ADL) earlier (p = 0.004, 0.001). ADL recovery was associated with on-time TAT ≤42 days on univariate analysis (OR 1.36, 95% CI 1.13-1.63, p = 0.001). TAT delay was less frequent with ERAS (51.3% vs. 69.2%), but this was not significant after multivariable logistic regression (p = 0.11). CONCLUSION:ERAS decreases LOS and returns advanced head and neck cancer patients to their ADL sooner. Postoperative ADL recovery independently predicts on-time adjuvant treatment. Still, compliance beyond 50% with the TAT ≤6 weeks CoC quality metric remains a major treatment barrier.

PURPOSE Little data exist regarding approaches to support oncology professionals who deliver cancer care for underserved populations. In response, ASCO developed the Serving the Underserved Task Force to learn from and support oncology professionals serving underserved populations. METHODS The Task Force developed a 28-question survey to assess oncology professionals' experiences and strategies to support their work caring for underserved populations. The survey was deployed via an online link to 600 oncology professionals and assessed respondent and patient demographic characteristics, clinic-based processes to coordinate health-related social services, and strategies for professional society support and engagement. We used chi-square tests to evaluate whether there were associations between percent full-time equivalent (FTE) effort serving underserved populations (<50% FTE v ≥50% FTE) with responses. RESULTS Of 462 respondents who completed the survey (77% response rate), 79 (17.1%) were Asian; 30 (6.5%) Black; 43 (9.3%) Hispanic or Latino/Latina; and 277 (60%) White. The majority (n = 366, 79.2%) had a medical doctor degree (MD). A total of 174 (37.7%) had <25% FTE, 151 (32.7%) had 25%-50% FTE, and 121 (26.2%) had ≥50% FTE effort serving underserved populations. Most best guessed patients' sociodemographic characteristics (n = 388; 84%), while 42 (9.2%) used data collected by the clinic. Social workers coordinated most health-related social services. However, in clinical settings with high proportions of underserved patients, there was greater reliance on nonclinical personnel, such as navigators (odds ratio [OR], 2.15 [95% CI, 1.07 to 4.33]) or no individual (OR, 2.55 [95% CI, 1.14 to 5.72]) for addressing mental health needs and greater reliance on physicians or advance practice practitioners (OR, 2.54 [95% CI, 1.11 to 5.81]) or no individual (OR, 1.91 [95% CI, 1.09 to 3.35]) for addressing childcare or eldercare needs compared with social workers. Prioritization of solutions, which did not differ by FTE effort serving underserved populations, included a return-on-investment model to support personnel, integrated health-related social needs screening, and collaboration with the professional society on advocacy and policy. CONCLUSION The findings highlight crucial strategies that professional societies can implement to support oncology clinicians serving underserved populations with cancer.

11019 Background: Studies show that <10% of patients with cancer participate in clinical trials. Pragmatica – Lung (SWOG S2302) utilizes a pragmatic approach for a registrational (FDA) trial that allows less data collection and broader eligibility, thus decreasing barriers to diverse enrollment. S2302 aims to improve overall and diverse accrual by using a novel trial design and multilevel community engagement. Methods: S2302 is a real-world randomized phase III registrational study comparing pembrolizumab + ramucirumab vs investigator-chosen standard therapy in 2nd line advanced/metastatic NSCLC. A multi-stakeholder recruitment plan was developed to improve diverse accrual (with initial focus on recruiting Black patients). The plan was vetted through SWOG communications and SWOG Lung Committee’s Working Group, DEI champion, patient advocate, and community engagement subcommittee. The DEI champion identified sites in the Southeast with high minority accrual in prior trials and completed directed informational visits. An external firm created culturally and linguistically appropriate patient education material, engaged sites with historically high accrual of Black and/or LatinX patients, leveraged advocacy partners to improve community awareness, and monitored enrollment by site. A monthly accrual report with demographic summaries (including age, sex, race, ethnicity) and site enrollment information is generated from SWOG Statistics and Data Management Center to monitor accrual rate and diversity. Results: From March through December 2023 (Table), the study accrued 37% of its goal and is enrolling above its target rate of 25 pts/mo averaging 36/mo over the last 5 months. Of enrolled pts, 58% are male, 13% are Black, and 3% are LatinX; from 59 academic, 67 community (13% rural), and 2 VA sites. Comparatively, LungMAP S1800A (the phase II precursor to S2302) accrued 7% Black and 1.5% LatinX pts with an average accrual of 9.2 pts/mo. Through November, the external firm contacted 24 site PIs (63% community-based), whose sites had collectively enrolled 16 pts, for a normalized pre-call rate of 0.1340 pts/mo. After contact and through November, these sites enrolled 23 pts, a rate of 0.3835 pts/mo – a 186% increase. Conclusions: The intentional, multi-pronged recruitment plan has exceeded historical overall, Black, and LatinX patient accrual rates. The data highlight novel approaches to trial design, recruitment strategies, and increased internal and external collaboration resulting in improved diversity of clinical trial enrollment and may be a potential toolkit for future trials. Support: NIH/NCI grants U10CA180888 and U10CA180819; and in part by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Eli Lilly and Company. Clinical trial information: NCT05633602 . [Table: see text]

TPS8657 Background: Most patients (pts) with advanced non-small cell lung cancer (NSCLC) will receive treatment with immunotherapy and develop tumor resistance. Several trials investigating combination therapy have not shown benefit over chemotherapy. Additional therapeutic options are needed. Complex clinical trials increase barriers to enrollment. Pragmatic trial designs may overcome challenges with accrual and representativeness in the appropriate setting. S1800A was a randomized phase II trial within Lung-MAP that showed a statistically significant improvement in overall survival (OS) with PR versus SOC for pts with advanced NSCLC who had tumor progression on prior chemotherapy and immunotherapy (JCO 2023). As a follow-on, we designed a pragmatic, randomized, registration intent trial to validate OS results and enhance representative accrual reflecting real-world practice. Methods: S2302 is a registration-intent randomized trial for pts who previously received PD-(L)1 inhibitor therapy for at least 84 days and platinum-based therapy, stratified by immediate prior line of therapy including PD-(L)1 inhibition (yes/no) and PS (0/1 v. 2). Pts are randomized to PR or investigator’s choice SOC (recommended to be based on NCCN guidelines). The primary objective is to compare OS between the arms. The only secondary objective is to summarize serious and unexpected high-grade (Grade 3-4) treatment-related adverse events and all Grade 5 adverse events. The accrual goal is 700 pts based on a design with 85% power to detect a hazard ratio of 0.77, using a 1-sided 2.5% level log-rank test. Estimated accrual duration is 24 months. As of January 2024, 286 pts were randomized, and enrollment is ongoing. S2302 Pragmatica-Lung presents a novel and potentially practice-changing paradigm to conduct a study with a combination of FDA approved drugs with well-known safety profiles and limited toxicity overlap. There are no onerous radiology or specimen requirements, and SOC treatment is provided as per FDA-approved package inserts and institutional policies. The goal is to empower practicing clinicians to enroll pts they see every day by reducing the study barriers and burden of clinical trial participation. The resulting pts enrolled will be more representative than other registration-intent trials. This approach allows the trial to reach more patients and holds the potential to better inform the field across a more representative set of pts with broader impact. Clinical trial information: NCT05633602 .

Importance Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain. Objective To evaluate the feasibility and safety of dental extractions immediately postradiation. Design, Setting, and ParticipantsA prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024. Exposure On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months. Main Outcomes and MeasuresThe primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients. Results Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis. Conclusions and Relevance This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Abstract INTRODUCTION American Indians (AI) have much higher incidence rates of lung cancer (LC) compared with non-Hispanic Whites (NHW) in the US. While low-dose computed tomography (LDCT) screening facilitates early detection of lung cancer, it is unknown how available LDCT screenings are to racially and geographically diverse populations in North Carolina (NC). To address this gap in knowledge, we conducted a descriptive study to characterize incident LC cases among AIs and NHWs, the distance from their location at diagnosis to the nearest LDCT screening facility and explored whether distance was associated with late-stage LC diagnoses. Methods Data were obtained from the Cancer Information and Population Health Resource (CIPHR), which comprise data from NC Central Cancer Registry (CCR) as well as public and private health insurance claims for the state. We identified ZIP codes and dates of rendered service for facilities providing LDCT by searching through claims from 2015-20. In addition, we identified incident LC cases among AIs and NHWs aged ≥18 years, from 2015-19. We assembled lists of LDCT facilities that existed in the year prior to each incident LC case. We calculated the minimum centroid to centroid distance to all facilities. Clinical attributes included age at diagnosis, sex, histology, stage at diagnosis, and rurality as measured by Rural Urban Commuting Area. Risk ratios were calculated for late-stage LC diagnoses across a range of thresholds for patient’s distance to nearest LDCT screening facility for AIs and NHWs. Results We identified 388 AI and 26,867 NHW incident LC cases in NC between 2015-20. Compared to NHWs, the median age at diagnosis for AIs was 5 years younger (AI: 65 vs. NHW: 69); more frequently male (AI: 54% vs NHW: 51%); and almost twice as likely to reside in rural areas (AI: 52% vs. NHW: 28%). There were no differences in late-stage LC diagnoses (AI: 54% vs. NHW: 52%). For distance (in miles) to the nearest LDCT screening facility, the median [Interquartile range] was twice as high for AIs (9.9 miles [0.8, 16.30]) compared to NHWs (5.3 miles [0, 12.1]). Among NHWs, there were statistically significant associations between distance and late-stage LC diagnosis at the shortest distance threshold of 5 miles (RR=1.04; 95%CL: 1.02, 1.07) through the threshold of 30 miles (RR=1.10 95%CL: 1.05, 1.15). There was no association across any distance threshold among AI lung cancer patients. Conclusions The large difference in accessibility of LDCT screening was not strongly associated with metastatic lung cancer diagnoses, possibly because so many patients were diagnosed late, reflecting poor early detection across all populations. We found that 80% of AIs with LC lived more than 10 miles away from LDCT screening facilities. This geographic distance may increase difficulty accessing cancer care geographically, and contribute to suboptimal LC screening rates. If efforts are to be made to increase early detection and improve survival, accessibility needs to be addressed on different dimensions. Citation Format: Bradford E. Jackson, Marc Emerson, Daniel Carrizosa, Chris Baggett, Lisa Spees, Joel Begay, Ana Salas, Yadurshirni Raveendran, Tomi Akinyemiju, Rachel Denlinger-Apte, Stephanie Wheeler, Ronny Bell. Missed Opportunities? Regional availability of Low Dose CT lung cancer screening facility locations in the year prior to diagnoses: A descriptive comparison of American Indian and Non-Hispanic White lung cancer patients in North Carolina [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 A132.

T-Cell Tumor Infiltration in Tissue-Matched Baseline (screening) and On-Treatment Metastatic Tumors (arm B parts 1 and 2)

Abstract BACKGROUND: Native Americans (NA) are an under-served population for healthcare, including lung cancer screening. Randomized trials have shown LDCT screening for lung cancer improves survival but with severe under-representation of NA due to financial and insurance constraints, geography and lack of access. They are over-represented in national statistics of presentation with advanced disease and lung cancer deaths. In our region, the Indian Health Service (IHS) has recorded less than 5% of eligible heavy smokers from the Catawba and other tribes have undergone LDCT lung screening. We previously reported that a free, mobile LDCT unit achieved a shift to earlier diagnosis in African Americans (AAs) and other under-served groups with improved 4 year survival and reduced costs of care (1).We adapted our initial trial to include a structured evaluation of efficacy and utility of mobile LDCT in heavy smokers in our NA population. We hypothesized that mobile LDCT would overcome key obstructions to lung cancer screening in NA. METHODS: We used a coach fitted with a portable 32 slice low-dose CT scanner; all films were reviewed by a central panel via the LUNGRADS protocol (1). Eligible subjects were invited to participate by IHS staff. Levine Cancer Institute committed to treat any identified cancers, irrespective of insurance status to avoid delay. Technical details of the unit have been reported (1). RESULTS: 91 heavy smokers have been screened, representing 60% participation rate, with the following characteristics: M:F=1:1; median age 61 years (44-77 years); 68% had some form of health insurance which did not cover lung cancer screening (termed "under-insured") and 32% were uninsured; 73% still smoking; median pack year history 48 (range 22-98). No lung cancers were identified but 10% had LUNGRADS 3-4 (moderate-high risk) lesions, 36% had LUNGRADS 2 lesions and 20% had scattered, non-diagnostic lung lesions; patients with LUNGRADS 4 lesions were offered biopsy to define whether cancer was present. All subjects have been recruited into ongoing follow up LDCT and smoking cessation programs. DISCUSSION: NA traditionally have had the highest level of advanced lung cancer at presentation with high mortality rate from lung cancer. We have increased participation in LDCT lung cancer screening from 5% to 60% of eligible heavy smokers, and have identified a unique sub-population of 10% with potentially premalignant disease that will require meticulous follow-up to achieve early diagnosis of lung cancer. Our previous studies in impoverished AAs and other under-served groups have identified a shift from 20% to 60% early stage cancer at diagnosis; similar benefits are expected in NAs. This is the first such study in NAs and suggests mobile LDCT should be considered by health services responsible for their care. Studies of the science of cancer in the under-served should also focus on pragmatic solutions with potential for early improvement in outcome. REFERENCES: 1. Raghavan D et al, The Oncologist, 2020, 25: e777-e781. Citation Format: Kia Dungan, Hollis Reed, Darcy Doege, Daniel Carrizosa, Melissa Wheeler, Derek Raghavan. Mobile low dose computerized tomographic (LDCT) scanning program identifies pre-malignant lung cancer lesions in a Native American population: A study of Indian Health Service and Levine Cancer Institute [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C110.

Objective: Small carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. Patients and methods: A retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. Results: From 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68-70.2 Gy in 33-35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (<= 2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1-28.8%). Conclusion: Small tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

Background: NRG1 fusions represent a rare and potentially actionable oncogenic alteration found in ~0.2% of solid tumors. Seribantumab is a fully human anti-HER3 IgG2 monoclonal antibody that blocks aberrant NRG1 fusion protein binding to HER3 thereby preventing ligand-dependent activation and dimerization resulting in complete inhibition of the PI3K/AKT and MAPK downstream signaling pathways. Seribantumab has shown significant anti-tumor activity in PDX models and in patients (pts) with solid tumors harboring NRG1 fusions. Methods: CRESTONE (NCT04383210) is a phase 2 study of seribantumab in adult pts with solid tumors harboring NRG1 fusions who received at least one prior therapy and were naïve to ERBB-targeted therapy (Cohort 1); pts previously treated with ERBB-targeted therapies (exploratory Cohort 2) and pts with tumors harboring additional molecular alterations (exploratory Cohort 3). Here, we present updated efficacy results for pts in Cohort 1 dosed at 3 g IV QW. Safety data are evaluated for pts enrolled in Cohort 1 and exploratory Cohorts 2 and 3. Results: As of Dec 2, 2022, 51 pts were enrolled across all cohorts with 30 pts in Cohort 1 dosed at 3 g IV QW. Median age was 62 years (range 19-84); median prior lines of therapy was 2 (range 1-7); tumor types included non-small cell lung cancer (NSCLC, n=30), pancreatic adenocarcinoma (PDAC, n=6), biliary tract/cholangiocarcinoma (CCA, n=6), breast (n=4), and others (n=5); 15 different NRG1 fusion partners were identified with CD74 (22%) and SLC3A2 (16%) as the most frequently reported. In the overall safety population, 41 pts (80%) reported at least one treatment-related adverse event (TRAE). The most common TRAEs (occurring in ≥20% of pts) were diarrhea (41%), fatigue (29%), rash (24%), and nausea (22%). Four pts (8%) experienced Gr 3/4 TRAEs; no Gr 5 TRAEs. The safety profile for Cohort 1 was similar to the overall safety population. Among the 30 pts in Cohort 1, 22 were evaluable for investigator assessed (INV) response per RECIST v1.1; 2 pts (9%) had confirmed complete response (CR), 6 pts (27%) had confirmed partial response (PR), and 13 pts (59%) had stable disease (SD) as their best overall response (BOR). The INV objective response rate (ORR, confirmed PR + CR) was 36% and disease control rate (DCR, confirmed PR+CR+SD) was 95%. The overall duration of response ranged from 1.4 to 17.2 months. In pts with NSCLC, the INV-ORR was 39% and DCR was 94%. Conclusions: Seribantumab has an acceptable safety and tolerability profile as a single agent in pts with solid tumors harboring NRG1 fusions. Updated efficacy data indicate seribantumab has robust and durable clinical activity, including CRs, across different tumor types harboring an NRG1 fusion and is a promising treatment option. Citation Format: Tejas Patil, Daniel R. Carrizosa, Mark E. Burkard, Karen L. Reckamp, Jayesh Desai, Young Kwang Chae, Stephen V. Liu, Kartik Konduri, Shirish M. Gadgeel, Jessica J. Lin, Parneet K. Cheema, David R. Spigel, Alison M. Schram, Valerie M. Jansen, Yasir Y. Elamin. CRESTONE: A Phase 2 study of seribantumab in adult patients with neuregulin-1 (NRG1) fusion positive locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT229.

Percentage lymphocyte subset Ki67+. All patient visits are binned by treatment cycle. Data at baseline and treatment cycle 3 were compared using the Wilcoxon signed rank test. All available data are illustrated; however, statistical comparisons were performed only for data available at both baseline and treatment cycle 3 (n=29).