TPS904 Background: Activating FGFR3 gene alterations have been identified in up to 20% of advanced/metastatic urothelial cancers (mUC). The pan-FGFR inhibitor erdafitinib (erda) is approved for the treatment of mUC with susceptible FGFR3 genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Since pan-FGFR inhibitors target all four isoforms of FGFR (1-4), their lack of FGFR isoform specificity can lead to off-target toxicity (e.g., hyperphosphatemia, stomatitis, ocular toxicity, skin and nail toxicity) and loss of activity due to development of on-target resistance mutations (e.g., V555M/L gatekeeper). TYRA-300 has been designed to be more selective for FGFR3 over FGFR1/2/4 to minimize off-target toxicity and to avoid interactions with known FGFR3 gatekeeper mutations. TYRA-300 is in development for the treatment of FGFR3 + mUC and other solid tumors (SURF301 - NCT05544552). Methods: SURF301 is a first-in-human, open-label, Phase 1/2 global study in several parts: dose escalation in participants with advanced malignancies, with/without FGFR3 alterations (Phase 1, Part A); dose expansion in participants with FGFR3 -activating mutations or fusions (Phase 1, Part B); and select tumor expansion cohorts with FGFR3 activating mutations or fusions (Phase 2). The purpose of Phase 1 is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity of TYRA-300, and identify the recommended Phase 2 dose (RP2D). Phase 2 will enroll participants in FGFR3 + mUC and other tumor types to further explore the anti-tumor activity and safety of TYRA-300. SURF301 study began enrolling patients in November 2022 and is ongoing in Australia, the United States, France, and Spain. Clinical trial information: NCT05544552 .

BackgroundNearly one-third of patients with newly diagnosed pancreatic cancer present with locally advanced disease (LAPC), with 25% eligible for surgical resection, lending to a poor 5-year overall survival of 16.2%. Given the significant morbidity and mortality associated with LAPC, timely integration of palliative and supportive care (SC) into the treatment care plan is vital. The purpose of this study was to investigate the utilization of SC in patients with LAPC and identify the demographic and socioeconomic factors that influence its application.Patients and methodsA retrospective database analysis of the National Cancer Database (NCDB) was carried out. Data regarding patients diagnosed with stage II-III LAPC between 2004 and 2018 were used. Analyses included tumor characteristics, demographics, socioeconomic parameters, and trends in utilization of SC.ResultsA total of 111 964 patients were included [stage II (72.3%); stage III (27.6%)]. Only 7.72% received SC despite 67% of patients receiving cancer-directed treatment at an academic or integrated network cancer program, 84% living in or near a metro area, and 60% living ≤20 miles of their primary treatment center. Rates of SC utilization remained <8% and <12% in stage II and III disease, respectively, throughout the two decades.ConclusionsSC has been underutilized in the LAPC population over the past two decades, despite the increase in data supporting early integration of palliative care and the potential sociodemographic areas of unmet need. Future work should focus on evaluating practice patterns across cancer centers and the potential positive impact of early SC integration on both survival and quality-of-life outcomes for patients with LAPC.

Alterations in glutamine metabolism have been proposed to play critical roles in cancer cell growth and survival. Mitochondrial glutaminase is a key enzyme in the conversion of glutamine to glutamate and is highly expressed in colorectal cancer (CRC). CB-839 is a potent and selective inhibitor of glutaminase, and synergistic activity in vitro and in vivo have been seen with CB-839 in combination with chemotherapy. We also demonstrated synergy between CB-839 and anti-EGFR monoclonal antibody therapy in multiple human CRC cell lines and that the combination could overcome anti-EGFR resistance. Given this preclinical data, we conducted a phase I/II study evaluating CB-839 with panitumumab. Our phase I results were presented earlier; here we present phase II. Study enrolled adult patients with metastatic, RAS wildtype CRC who achieved at least stable disease from prior anti-EGFR therapy. Patients were treated at the recommended phase II dose from phase I: 6 mg/kg panitumumab biweekly and 800 mg/kg daily CB-839 800 mg/kg in 28-day cycles. Imaging was assessed every eight weeks and the primary endpoint was response rate (RR). Enrollment followed a Simon’s two-stage design that required at least one response in the first 10 patients to continue. A sample size of 29 patients would provide 80% power to reject the null hypothesis of low efficacy (RR£5%) with a true RR of 20%. Correlative studies included two research PET scans (baseline and after one cycle) using 18F-FSPG, which provides a measurement of glutamine metabolism, and baseline tumor biopsies for RNA-seq. Seventeen patients were enrolled [median age, 52; male (71%); white (77%)]. All had received at least three prior lines of therapy for metastatic disease. Two responses were observed at the interim analysis and the study continued. Unfortunately, the development of CB-839 was discontinued and the study closed. Of the 17 patients enrolled, 15 were evaluable for efficacy. The RR was 13.3% (2/15) and the disease control rate was 46.7% (7/15). The median progression-free survival (PFS) and overall survival (OS) was 2.23 months and 8.87 months, respectively. At six months, the PFS and OS rates were 20.1% and 50.1%, respectively, while the OS rate at 12 months was 28.7%. The most frequently reported toxicities were: rash (70.6%); hypomagnesemia and nausea (35.3%); elevated alanine aminotransferase (29.4%); fatigue, paronychia, and vomiting (23.5%). Most were Grade 1 or 2. Eight patients had two research PET scans; preliminary analysis demonstrated a positive correlation (R2=0.37) with change in 18F-FSPG uptake and lesion diameter, suggesting lesions that are responding to treatment have less tracer accumulation. RNA-seq analysis is ongoing and will be presented. Panitumumab and CB-389 was very tolerable with some efficacy in heavily pre-treated patients. Early analysis of PET imaging data suggests a potential relationship between 18F-FSPG uptake and response, but additional studies are needed. It is anticipated that RNA-seq will identify genes that are related to glutamine avidity and represent a key determinate of response to inhibitors of glutamine metabolism.

This article summarises expert discussion on the management of patients with hepatocellular carcinoma (HCC), which took place during the 24th World Gastrointestinal Cancer Congress (WGICC) in Barcelona, July 2022. A multidisciplinary approach is mandatory to ensure an optimal diagnosis and staging of HCC, planning of curative and therapeutic options, including surgical, embolisation, ablative strategies, or systemic therapy. Furthermore, in many patients with HCC, underlying liver cirrhosis represents a challenge and influences the therapeutic options.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Neurotrophic tyrosine receptor kinase ( NTRK ) gene fusions are oncogenic drivers in various tumour types. Larotrectinib is a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor approved for use in adult and paediatric patients with TRK fusion cancer, demonstrating an objective response rate (ORR) of 41% across 18 patients with gastrointestinal (GI) cancer (Boni et al, WCGI 2021). We report an updated analysis from an expanded dataset of patients with TRK fusion GI cancer with longer follow-up. Patients with TRK fusion GI cancer treated with larotrectinib in the phase II clinical trial NAVIGATE (NCT02576431) were included in this analysis. Responses were investigator-assessed using RECIST v1.1. Data cut-off was 20 July 2021. As of data cut-off, 34 patients with metastatic TRK fusion GI cancer were enrolled. Median age was 63.5 years (range 32–90). The tumour types included were colorectal (CRC; n=19), pancreatic (n=6), cholangiocarcinoma (n=4), appendiceal (n=1), duodenal (n=1), gastric (n=1), hepatocellular carcinoma (n=1) and oesophageal (n=1). Among the patients with CRC, 10 were microsatellite instability high (MSI-H), seven were MSI-H not detected (including stable) and two were unknown. Overall, 32%, 35% and 18% of patients had received 1, 2, or ≥3 prior lines of systemic therapy, respectively. ORR in the 33 evaluable patients was 33% (95% confidence interval [CI] 18–52): one complete response (CR; 3%), 10 partial responses (PR; three pending confirmation [30%]), 15 stable disease (SD; 45%), four progressive disease (PD; 12%) and three not determined (ND; 9%). Median time to response was 1.9 months (range 1.7–5.0). Median duration of response (DoR) was 7.3 months (95% CI 3.5–27.3); median follow-up was 26.4 months. Median progression-free survival (PFS) was 5.4 months (95% CI 2.7–9.0); median follow-up was 5.4 months. Median overall survival (OS) was 12.5 months (95% CI 6.1–33.4); median follow-up was 7.7 months. In the 19 patients with CRC, ORR was 47% (95% CI 24–71): one CR (5%), eight PR (three pending confirmation [42%]), eight SD (42%), one PD (5%) and one ND (5%). Of the nine responders, six were MSI-H. The median DoR was not reliably estimable, but the 12-month rate was 67% (95% CI 29–100); median follow-up was 17.8 months. Median PFS was 5.5 months (95% CI 2.7–not estimable); median follow-up was 5.6 months. Median OS was 12.5 months (95% CI 6.1–36.5); median follow-up was 7.8 months. Treatment duration for all GI patients ranged from 0.2+ to 32.2+ months. At data cut-off, 14 patients had progressed; four continued treatment post-progression for ≥4 weeks. Treatment-related adverse events (TRAEs) occurred in 65% of patients (27% were Grade [G]1, 21% G2, 12% G3 and 6% G4). No patients discontinued treatment due to TRAEs. In this expanded dataset with longer follow-up, larotrectinib continues to demonstrate rapid, durable responses, extended survival and a favourable safety profile in patients with TRK fusion GI cancer, particularly in those with CRC. These results highlight the importance of identifying NTRK gene fusions in patients with GI cancer, particularly in those with MSI-H CRC.

The APACT trial evaluated the safety and efficacy of adjuvant nab -P + Gem vs Gem alone in patients with resected PC. Between April 2014 and April 2016, 866 patients were randomized. As previously reported, APACT did not meet the primary endpoint of independently assessed disease-free survival (DFS); however, the prespecified sensitivity analysis for median investigator-assessed DFS was 16.6 months with nab -P + Gem and 13.7 months with Gem (HR, 0.82; 95% CI, 0.694–0.965; nominal P=0.0168). The overall survival (OS; secondary endpoint) at the time of the primary analysis trended in favor of nab -P + Gem: median 40.5 vs 36.2 months (427 events; 68% mature; HR, 0.82; 95% CI, 0.680–0.996; nominal P=0.045).

NUC-3373 is a novel phosphoramidate nucleotide analogue that generates high intracellular levels of the anti-cancer metabolite fluorodeoxyuridine-monophosphate (FUDR-MP). Fluoropyrimidines, such as 5-FU and capecitabine, exert their main anti-cancer activity via FUDR-MP, which binds and inhibits thymidylate synthase (TS), disrupting DNA synthesis and repair. Fluoropyrimidines also result in the generation of the toxic metabolites FBAL and FUTP. NUC-3373, a targeted TS inhibitor, is designed to bypass the 5-FU and capecitabine resistance mechanisms associated with transport, activation and breakdown and to reduce the generation of toxic metabolites such as FBAL and FUTP.

Larotrectinib is a first-in-class, highly selective, central nervous system (CNS)-active tropomyosin receptor kinase (TRK) inhibitor approved in over 40 countries, and by the European Medicines Agency, for the treatment of adult and paediatric patients with TRK fusion cancer. In a previous analysis, larotrectinib demonstrated clinical benefit across varying degrees of pre-treatment or performance status in 159 patients with TRK fusion cancer. Here, we report updated data on larotrectinib outcomes stratified by prior lines of systemic therapy and baseline performance status.

3108 Background: Neurotrophic tyrosine receptor kinase ( NTRK) gene fusions encode tropomyosin receptor kinase (TRK) fusion proteins, which are oncogenic drivers in various tumor types. Larotrectinib is a first-in-class, highly selective, CNS-active TRK inhibitor approved to treat adult and pediatric patients with TRK fusion cancer. Larotrectinib demonstrated an objective response rate (ORR) of 78% and a median progression-free survival (PFS) of 36.8 months in an integrated analysis of 175 patients with non-primary CNS TRK fusion cancer (McDermott et al, ESMO 2020). We report updated efficacy and safety data with longer follow-up in an expanded dataset. Methods: Data were pooled from three clinical trials of patients with non-primary CNS TRK fusion cancer treated with larotrectinib. Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Response was assessed by investigators using RECIST v1.1. Data cutoff: July 20, 2020. Results: As of data cutoff, 218 patients were treated with larotrectinib, of which 206 were evaluable for efficacy. There were 21 different tumor types, the most common being soft tissue sarcoma (STS [46%], including infantile fibrosarcoma [20%] and other STS [26%]), thyroid (13%), salivary gland (11%), lung (9%), and colorectal (5%). The median age was 38.0 years (range 0.1–84.0). Patients were heavily pretreated with 45% having received 2 or more prior lines of systemic therapy; 27% had 0 prior lines of systemic therapy. The ORR was 75% (95% CI 68–81): 45 (22%) complete response, 109 (53%) partial response (PR), 33 (16%) stable disease (SD), and 13 (6%) progressive disease (PD). Nineteen patients had brain metastases at baseline, with 15 evaluable for efficacy. The ORR for patients with brain metastases was 73% (95% CI 45–92): 11 PR, 2 SD, and 2 PD. Among all evaluable patients, the median time to response was 1.8 months (range 0.9–9.1). With a median follow up of 22.3 months, the median duration of response was 49.3 months (95% CI 27.3–not estimable). Treatment duration ranged from 0.03+ to 60.4+ months. Median PFS was 35.4 months (95% CI 23.4–55.7) with a median follow up of 20.3 months. At a median follow-up of 22.3 months, median overall survival (OS) was not reached and 36-month OS was 77% (95% CI 69–84). Treatment-related adverse events (TRAEs) were mainly Grade 1–2, with 18% having Grade 3–4 TRAEs. Only 2% of patients discontinued due to TRAEs. Conclusions: These results highlight the importance of testing for NTRK gene fusions in patients with cancer because the majority of patients with TRK fusion cancer treated with larotrectinib had long-term clinical benefit. The safety profile continued to be favorable and no new safety signals were identified. Clinical trial information: NCT02576431, NCT02122913, NCT02637687.

Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in a range of adult and pediatric malignancies but are generally rare in patients with gastrointestinal (GI) cancer, with a prevalence of around 0.3% in colorectal cancer (CRC; Forsythe et al, Ther Adv Med Oncol 2021). Larotrectinib is a first-in-class, central nervous system (CNS)-active, highly selective tyrosine receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion-positive cancer, demonstrating an objective response rate (ORR) of 78% across 175 adult and pediatric patients with various non-CNS cancers (McDermott et al, ESMO 2020). We report data on an expanded dataset of patients with TRK fusion-positive GI tumors. Patients with TRK fusion-positive GI cancer treated with larotrectinib in the phase II clinical trial NAVIGATE (NCT02576431) were included in this analysis. Response was investigator-assessed using RECIST v1.1. As of July 20, 2020, 18 patients with metastatic TRK fusion-positive GI cancer were enrolled. Median age was 67.0 years (range 32.0 to 84.0 years). Of the 10 patients with CRC, 7 were microsatellite instability-high (MSI-H), 2 were microsatellite stable (MSS) and phenotype was unknown in 1 patient. The other tumor types were cholangiocarcinoma (n=3), pancreatic (n=2), appendiceal (n=1), esophageal (n=1), and hepatocellular carcinoma (n=1). Overall, 13 patients (72%) had received ≥2 prior lines of therapy, 3 (17%) of whom had received immunotherapy. The best response to last prior therapy was 2 partial responses (PR), 6 stable disease (SD), 3 progressive disease (PD), and 7 unknown, unevaluable or not applicable. ORR in the 17 evaluable patients was 41% (95% CI 18–67): 1 complete response (CR), 6 PR (1 pending confirmation), 7 SD, 2 PD and 1 not determined. Median time to response in the 6 confirmed responders was 1.9 months (range 1.7 to 5.0 months). Median duration of response (DoR) was 5.5 months (95% CI 3.5–27.3). Median progression-free survival (PFS) was 5.4 months (95% CI 2.2–11.6) at a median follow-up of 20.3 months. Median overall survival (OS) was 14.1 months (95% CI 2.8–33.4) at a median follow-up of 7.8 months. In the 10 patients with CRC, ORR was 50% (95% CI 19–81): 1 CR, 4 PR (1 pending confirmation), and 5 SD. For these patients, median DoR was 15.5 months (95% CI 3.7–27.3), median PFS was 5.5 months (95%CI 2.2–29.4) and median OS was 29.4 months (95% CI 2.8–36.5). Duration of treatment for all GI patients ranged from 0.26+ to 29.3 months. At data cut-off, 10 patients had progressed, with 3 continuing treatment post-progression. Adverse events were mostly Grade 1–2. Treatment-related adverse events (TRAEs) occurred in 11 patients. Grade 3/4 TRAEs occurred in 2 patients (increased alanine aminotransferase, increased aspartate aminotransferase, and nausea). There were no treatment discontinuations due to TRAEs. In patients with TRK fusion-positive GI cancer, larotrectinib demonstrated rapid responses with high survival rates and a favorable safety profile. These results support testing for NTRK gene fusions in patients with GI cancer, particularly in patients with MSI-H CRC.

5-FU is a key anti-cancer agent used across a broad range of tumours. The anti-cancer metabolite of 5-FU, fluorodeoxyuridine-monophosphate (FUDR-MP), binds and inhibits thymidylate synthase (TS), disrupting DNA synthesis and repair. 5-FU is often dosed with leucovorin (LV) to enhance binding of FUDR-MP to TS. NUC-3373 is a phosphoramidate transformation of FUDR-MP designed to bypass 5-FU resistance mechanisms associated with transport, activation and breakdown. NuTide:302 is a three-part study in patients (pts) with advanced colorectal cancer (CRC) who have relapsed after ≥2 prior lines of 5-FU-containing regimens, investigating NUC-3373 in combination with agents commonly used to treat CRC. Pts received 1500 mg/m2 NUC-3373 +/- 400 mg/m2 LV on Days 1 and 15 of a 28-day cycle. Plasma and PBMC samples were collected during first 2 cycles. Safety was assessed throughout. PK profiles from 17 matched pairs from Q2W dosed pts were available (n = 21 pts). PK parameters for NUC-3373 were similar +/- LV and interpatient variability was low. Increasing intracellular FUDR-MP concentrations were associated with an increase in intracellular dUMP concentrations. NUC-3373 was well tolerated +/- LV. Highest grade treatment-related adverse events (TRAEs) were grade 3 hyponatremia (1 pt) and grade 4 bilirubin increased (1 pt). No pts discontinued NUC-3373 due to TRAEs.Table: 464PNUC-3373 + LV Mean (%CV)NUC-3373 Mean (%CV)Cmax(ug/ml)42.1 (32)39.6 (37)AUC (0-t)(ug·h/ml)149.0 (68)135.0 (77)Elimination half-life (hours)5.1 (25)5.0 (26)Volume of distribution (L)174 (45)193 (41)Clearance (L/hour)27.0 (49)30.9 (49) Open table in a new tab NUC-3373 demonstrated a favourable PK profile with a long plasma half-life and high volume of distribution. The association between increasing FUDR-MP with increasing dUMP concentrations indicates NUC-3373's ability to inhibit TS, preventing conversion of dUMP to dTMP. PK parameters for NUC-3373 +/- LV were similar indicating LV has no PK interaction with NUC-3373. NUC-3373 was well tolerated +/- LV. These findings suggest that LV is an appropriate combination partner for NUC-3373.

Stimulation of the immune system to generate antitumor response represents a compelling therapeutic strategy, especially in settings where only some patients (pts) achieve response. ABBV-368 is a novel, immunoglobulin G1 anti-OX40 monoclonal antibody agonist that elicits tumor responses by stimulating effector T cells and inhibiting regulatory T cells (Le Tourneau et al. SITC. 2019;432). Tilsotolimod is a synthetic TLR9 agonist with immunostimulatory activity (Babiker et al. AACR. 2020;134). Budigalimab (ABBV-181) is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting PD-1 modified to reduce Fc receptor interactions and limit effector function. This phase Ib, multicenter, open-label study (NCT04196283) is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ABBV-368 in combination with tilsotolimod and other agents (± nab-paclitaxel and budigalimab) in pts with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (SCC). Pts ≥18 years with histologically confirmed SCC (of the oral cavity, oropharynx, larynx, or hypopharynx) with ≥1 lesion accessible for intratumoral (IT) injection, are eligible. Pts must have an ECOG performance status of 0 or 1, a life expectancy of ≥3 months, received 1 prior immunotherapy regimen (including a PD-(L)1 inhibitor), and have ≤3 prior treatments in the R/M setting. Pts with uncontrolled CNS metastases and those who have received prior OX40 or TLR agonist treatment (excluding topical agents) are ineligible. Pts in Arm 1 will receive intravenous (IV) ABBV-368 plus tilsotolimod (IT); pts in Arm 2, ABBV-368 + tilsotolimod + IV nab-paclitaxel; and pts in Arm 3, ABBV-368 + tilsotolimod + nab-paclitaxel and IV budigalimab. Primary objectives are to assess safety, tolerability, and pharmacokinetics of these combinations. Secondary objectives are to assess objective response rate, clinical benefit rate, time to response, progression-free survival, and duration of response. Paired biopsy samples will be taken for exploratory analysis. Planned enrollment is 69 pts. NCT04196283. Medical writing support was provided by Devon Roll, PhD, of Bio Connections, LLC. AbbVie, Inc. AbbVie, Inc. funded this study.

Larotrectinib is a first-in-class, CNS-active, EMA- and FDA-approved selective tropomyosin receptor kinase (TRK) inhibitor. TRK proteins are encoded by the NTRK genes; gene fusions involving NTRK are rare oncogenic drivers seen in a range of paediatric and adult tumour types. Pooled analysis of three clinical trials showed that larotrectinib induced an investigator-assessed overall response rate (ORR) of 79%, median progression-free survival (PFS) of 28.3 months (95% CI 22.1–NE) and median overall survival (OS) of 44.4 months (95% 36.5–NE) in 159 patients (pts) with TRK fusion cancer (Hong et al, Lancet Oncol. 2020). Here we report updated survival data with longer follow-up in an integrated dataset of 175 pts with TRK fusion cancer treated with larotrectinib. Data were pooled from three clinical trials of pts with non-primary CNS TRK fusion cancer treated with larotrectinib. Disease status was assessed by investigators using RECIST v1.1. Primary endpoint was ORR and secondary endpoints included PFS, OS, duration of response (DoR) and safety outcomes. Data cut-off: 15 July 2019. A total of 175 pts were included in the integrated dataset. The median age was 43 y (range 0.1–84.0). The ORR was 78% (95% CI 71–84): 19% complete response, 59% partial response, 13% stable disease and 7% progressive disease. Median DoR was not estimable (NE) at a median follow-up of 13.5 months, with a 12-month DoR rate of 81% (95% CI 73–89). At a median follow-up of 13.8 months, median PFS was 36.8 months (95% CI 25.7–NE), showing extended benefit compared to previous analysis. Although median OS had not been reached with a median follow-up of 15.3 months, the 12-month OS rate was 90% (95% CI 85–95). Larotrectinib-related adverse events (AEs) were mainly Grade 1/2 with no new safety signals identified; two pts discontinued due to larotrectinib-related AEs. These data confirm that treatment with larotrectinib offers extended survival benefit in pts with TRK fusion cancer. Larotrectinib continued to demonstrate a favourable long-term safety profile. Screening pts for NTRK gene fusions should be actively considered.

Introduction: Patients with pancreatic cancer (PC) have a poor prognosis. Even with resectable PC, the 5-year postsurgical survival rate is only ≈ 20%. Furthermore, surgical resection is associated with postoperative morbidity and diminished quality of life (QoL). In metastatic PC, nab-paclitaxel plus gemcitabine (nab-P/Gem) demonstrated significantly longer overall survival (OS) than gemcitabine (Gem) alone. The phase III APACT trial aimed to assess the efficacy and safety of nab-P/Gem vs Gem monotherapy in patients with surgically resected PC.

Introduction: Pancreatic cancer (PC) is associated with a poor prognosis and has the lowest survival rates among all cancers. The 5-year survival rate is < 10% for all stages of PC combined, which reflects the frequently advanced disease stage at diagnosis. In fact, < 20% of patients are candidates for resection at diagnosis. The phase III, international, open-label, APACT trial assessed the efficacy and safety of nab-paclitaxel plus gemcitabine vs gemcitabine alone in treatment-naive patients with surgically resected PC. Given the low prevalence of resectable cases at diagnosis among patients with PC, we report the process for patient identification and reasons for exclusion in APACT. Methods: Patients aged ≥ 18 years with histologically confirmed pancreatic adenocarcinoma with macroscopic complete resection (R0 and R1) were eligible. Key inclusion criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1, acceptable blood chemistry levels (absolute neutrophil count ≥1500/mm3, platelet count ≥ 100,000/mm 3, hemoglobin ≥ 9 g/dL, total bilirubin ≤ upper limit of normal), PC surgical staging (T1-3, N0-1, M0), and a CA19-9 level < 100 U/mL within 14 days of randomization. Patients with presence of or a history of metastatic or locally recurrent PC or those who previously received systemic treatment (including neoadjuvant) for PC were excluded. During the screening period, patients were assessed by computed tomography scan performed within 14 days before randomization. Treatment was to be started within 12 weeks following surgery. Results: Overall, 1226 patients were screened for eligibility; of these, 360 (29%) were excluded during screening. Patients may have had ≥ 1 reason for exclusion. The most common reasons for exclusion were CA19-9 > 100 U/mL (10%), metastatic disease (7%), unacceptable blood chemistry levels (4%), PC surgical staging of > T3 or M1 (3%), and unwillingness or inability to comply with study protocol (2%). In addition, some patients (≈ 1% in each of the following scenarios) were excluded due to inability to adhere to study schedule and requirements, ineligible histology, significant medical condition, unacceptable hematology parameters, another malignancy within 5 years of randomization, serious medical risk factors, or inability to start treatment within 12 weeks after surgery. Conclusion: Among patients with surgically resected PC, 29% of those screened were deemed ineligible for inclusion in the APACT trial. The screening process may have helped to identify patients who were most likely to be able to complete 6 cycles of adjuvant chemotherapy. NCT01964430.