Tan, Benjamin

4183 Background: High grade neuroendocrine neoplasms (HG-NENs) are treated with platinum doublets mirroring guidelines for small cell lung cancer (SCLC) but recurrences are common and salvage options are limited in efficacy. Cabozantinib (CABO), an inhibitor of VEGFR, MET, and TAM kinases (TYRO3, AXL, and MER) was approved by the FDA for treatment of well differentiated (WD) NENs of both pancreatic and extrapancreatic origins based on the CABINET study (Chan, NEJM 2025). However, its efficacy in the whole spectrum of HG-NEN patients including poorly differentiated disease (PDD) has not been prospectively explored. Methods: This was a single institution, Phase II study of CABO in patients with HG-NENs who had progressed on at least one prior treatment. Key inclusion/exclusion criteria were NENs of any origin except SCLC, high grade by Ki-67 of > 20% or histology consensus, ECOG of < = 1, appropriate hematological parameters and no history of bleeding or active cardiac disease. CABO was given orally starting at 60 mg po daily in 3-week cycles. The primary endpoint of this study was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). A Simon optimal 2-stage design tested the null hypothesis that the true ORR is < = 1% at the type I error rate of 5%, resulting in projected enrollment of up to 32 total patients. Toxicities were graded according to CTCAE v5.0 and response was evaluated according to RECIST v1. Results: All patients have been accrued, with 4/32 patients still on treatment. Median age at diagnosis was 62 years and male to female ratio was 1.46. Origin of tumor was GI in 68.8% of the cases, the rest being thoracic (6.3%), prostate (6.3%) cervical (6.3%) head/neck (3.1%) and unknown (9.4%). Median Ki-67 was 55%, 11 patients had Ki-67 > 70%. Histology was WD-HG in 40% of patients and PDD in 60%. Two patients had mixed PDD/other components (MiNEN). Median PFS in evaluable patients was 4.01 months [95% CI 1.61 to 9.30] and mOS was 9.89 mo [95% CI 6.73 to 18.96]. Three patients so far (9.3%) have had partial response as best response (PDD-colon, WD-pancreas and PDD-cervical) while 19/32 (59.4%) patients have had stable disease as best response so far (disease control rate 68.8%). Five (15.6%) patients have received more than 10 treatment cycles. The three longest treated patients had WD-pancreas (23 and 17 cycles) and PDD-unknown (12 cycles). One patient had eventual resection of a metastatic site and is currently without evidence of disease. Three patients withdrew from the trial because of toxicities (shortness of breath, GI bleeding, thromboembolism). Twenty-six patients have expired. Conclusions: CABO monotherapy showed efficacy in some HG-NEN patients with not just WD but also the very aggressive PDD histology. No new side effects to the ones previously described for this agent were noted. Supported by Exelixis and a Siteman investment program grant. Clinical trial information: NCT04412629 .

4122 Background: BTCs are rare and aggressive malignancies. The first-line standard of care regimen for advanced BTC (aBTC) is gemcitabine (GEM), cisplatin, and an immune checkpoint inhibitor. Although FOLFOX is a preferred second-line treatment, it is limited by neuropathy. Nal-IRI contains IRI free base in liposome nanoparticles, which shelter IRI from conversion to its active metabolite (SN-38) and increase intratumoral SN-38 compared with IRI alone. The NAPOLI-1 trial of FU/LV/nal-IRI vs. FU/LV in second-line advanced pancreatic adenocarcinoma showed an overall survival (OS) benefit. The NIFTY trial (South Korea) demonstrated median OS (mOS) benefit of FU/LV/nal-IRI over FU/LV in a second-line aBTC population (8.6 vs. 5.3 months [mo], HR 0.68, 95% CI 0.48-0.95); however, the NALIRICC trial (Germany) did not (6.9 vs. 8.2 mo, HR 1.08, 95% CI 0.68-1.72). We sought to characterize second-line FU/LV/nal-IRI efficacy in US patients (pts) with second-line aBTC. Methods: This was a single-arm, open-label, multicenter phase II study of pts with aBTC previously treated with GEM/platinum chemotherapy. Pts received nal-IRI 70 mg/m 2 IV over 90 minutes, LV 400 mg/m 2 IV over 30 minutes every 14 days, and FU 2400 mg/m 2 IV over 46 hours every 14 days. The primary objective was to determine progression-free survival rate at 4 mo (PFS 4mo ) using RECIST v. 1.1 criteria. Median PFS reported for pts receiving second-line 5-FU doublet chemotherapy was 3 mo with a PFS of 30%. FU/LV/nal-IRI was of interest if it could increase the PFS 4mo to 50% or higher. Using a one-sided α of 0.05 and 80% power, 17 of 39 evaluable pts had to be progression-free at 4 mo to detect a difference in PFS 4mo between 30% and 50%. Results: Forty-eight pts were enrolled: median age 64.5 years; 69% women; 27% gallbladder primary; 54% intra- and 19% extrahepatic. Ten pts came off study due to toxicity without disease progression before 4 mo on study and were replaced to evaluate the PFS 4mo endpoint. Of 38 evaluable pts, 18 pts (PFS 4mo 47%) were alive and progression-free at 4 mo, meeting the primary endpoint. With a median follow-up of 7.1 mo, median time to disease progression or study discontinuation due to toxicity for all pts was 2.3 mo (95% CI 1.8-4.6, PFS 4mo 38%), and for pts evaluable for the primary endpoint, median PFS was 3.5 mo (95% CI 1.8-5.5). Five pts (10%) had PFS beyond 12 mo. mOS for all pts was 7.9 mo (95% CI 5.7-11.7). Of 41 evaluable pts, the response rate was 2% (1 PR), and the disease control rate was 54%. Adverse events (AEs) were consistent with known toxicities from the FU/LV/nal-IRI regimen. Conclusions: FU/LV/nal-IRI is an effective second-line regimen for aBTC in US pts. There was significant early toxicity as 21% of pts came off study due to AEs before 4 mo. Correlative studies, including longitudinal analyses of circulating tumor DNA using banked blood specimens, are planned (NCT04005339). Clinical trial information: NCT04005339 .

LBA3509 Background: Systemic inflammation has been implicated in colon cancer progression. We examined whether intake of a proinflammatory diet is associated with survival among patients (pts) with stage III colon cancer. Methods: This prospective cohort study was nested within a randomized phase III trial of adjuvant therapy in pts with stage III colon cancer who had undergone curative-intent resection. EDIP score – a validated tool to classify the inflammatory nature of diets – was derived as a cumulative exposure using data from food-frequency questionnaires completed within 6 weeks of randomization and 14-16 months (mo) after randomization. Cox proportional hazards regression was used to assess the associations of EDIP with disease-free survival (DFS) and overall survival (OS). Results: Of 1625 included pts, the mean (SD) age was 60.9 (10.5) years (yrs). Compared to pts in the lowest EDIP quintile, pts in the highest quintile (a more inflammatory diet) were younger (58.7 ± 10.8 vs 61.3 ± 9.5 yrs old) and more likely to be female (64.0% vs 48.9%) and have worse performance status (ECOG 1-2: 35.7% vs 19.4%). Pts in the highest quintile were less likely to be White (76.6% vs 92.0 %) and more likely to be Black (15.4% vs 3.7%). Baseline aspirin use, assigned chemotherapy (3 mo vs 6 mo), and assigned pharmacotherapy (celecoxib vs placebo) were not significantly different across EDIP quintiles. Compared with pts in the lowest EDIP quintile, pts in the highest quintile had significantly worse OS (multivariable hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.26-2.77, P trend =0.01), but not DFS (HR 1.36, 95% CI 0.99-1.86, P trend =0.22). Diet and physical activity jointly influenced OS. Those with lower EDIP scores (quintiles 1-4, 80% of the study population) and higher physical activity (≥9 MET-h/wk) had the best OS (HR 0.37, 95% CI 0.25-0.53) compared with pts in the highest EDIP quintile (20% of the study population) and lower physical activity (<9 MET-h/wk) ( P interaction <0.001). The association between higher EDIP and OS was consistent when analyzed by celecoxib and placebo treatment arms ( P interaction 0.54). The relationship between EDIP and OS did not differ significantly according to aspirin use, with HR 1.60 (95% CI 0.71-3.60) among aspirin users and HR 2.01 (95% CI 1.27-3.16) among aspirin non-users ( P interaction 0.06). Conclusions: Our findings suggest that greater intake of a proinflammatory dietary pattern is associated with worse OS in pts with stage III colon cancer. Regular physical activity may attenuate the association, and further investigation of diet and physical activity intervention is warranted. Support: U10CA180821, U10CA180882, U24CA196171, U10CA180863, CCS 707213, UG1CA233234, U10CA180820, U10CA180868, U10CA180888; https://acknowledgments.alliancefound.org. Pfizer; ClinicalTrials.gov Identifier: NCT01150045.

TPS3648 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes tryptophan along the kynurenine pathway and is recognized as a potent suppressor of tumor reactive immunity. Epacadostat is an orally active, potent and selective inhibitor of IDO1. In preclinical studies, IDO1 was found to promote resistance to radiation in rectal cancer, irrespective of microsatellite instability (MSI) status. IDO1 inhibition with epacadostat improved tumor radiosensitivity by relieving immune suppression and augmenting radiation-induced apoptosis while protecting the normal intestine from radiation damage. In a phase 1 trial, 17 patients were enrolled from 4/2019 to 8/2023. Epacadostat in combination with short-course radiation therapy (SCRT) and CAPOX was well-tolerated and the recommended phase 2 dose (RP2D) of epacadostat was determined to be 400 mg BID. An NCI supported Phase 2 trial is ongoing to further evaluate the promising disease responses reported in the dose escalation phase. Methods: This phase 2 multicenter, open-label trial includes treatment and biomarker cohorts. In the treatment cohort, epacadostat at 400 mg BID will be administered concurrently with SCRT followed by epacadostat monotherapy until 1 day prior to neoadjuvant chemotherapy, followed by standard-of-care (SOC) neoadjuvant chemotherapy and, ultimately, surgical resection or non-operative management (NOM). Biomarker cohort enrollment will commence at completion of treatment cohort accrual. Enrolled patients will be treated with SOC SCRT followed by SOC neoadjuvant chemotherapy and surgical resection or NOM. Eligible patients must be a treatment-naïve, newly diagnosed, pathologically confirmed, locally advanced rectal cancer (defined by 8 th edition AJCC stage 2 or 3, or stage 1 not eligible for sphincter-sparing surgery) with plans to proceed with neoadjuvant SCRT and chemotherapy. The primary endpoint is the neoadjuvant rectal (NAR) score. Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate and progression-free survival (PFS). Exploratory endpoints are pharmacodynamics, PDX and organoid generation, identification of molecular predictors of response and resistance, correlation of radiographic and pathologic response and effect of treatment on patient quality of life. We aim to enroll 27 patients in the treatment cohort and 10 in the biomarker cohort. Clinical Trial Registration: NCT03516708 .

3624 Background: Increasing chemotherapy completion and reducing chemotherapy adverse events (AE) are critical to improve survival after colon cancer diagnosis. Sex, as a biological variable, may impact chemotherapy treatment differently, and thus further investigation is needed to examine sex differences in chemotherapy completion and adverse events among patients with colon cancer. Methods: Among an NCI-sponsored trial conducted among patients with stage III colon cancer (CALGB/SWOG 80702), all patients received standard adjuvant chemotherapy FOLFOX (fluorouracil, leucovorin, and oxaliplatin). To signal chemotherapy completion, we utilized relative dose intensity (RDI) calculated as the ratio of the delivered dose intensity to planned dose intensity; and reduced RDI (RDI <85%) was considered as a clinically significant deviation from standard FOLFOX. From clinicians’ records of NCI’s Common Terminology Criteria for Adverse Events (CTCAE), we primarily focused on clinically significant AE such as neutrophils decrease, nausea, platelets decrease, hypertension, peripheral neuropathy, diarrhea, fatigue, gastritis, creatinine increase, gastric ulcer, myocardial ischemia, and cerebral ischemia; and severe AE was defined as the occurrence of any above AE with CTCAE grade ≥3. Using multivariable logistic regression that adjusted for body surface area (BSA) and other clinicopathological confounders, we estimated adjusted odds ratios (OR) for the associations of sex with reduced RDI and severe AE. Results: Of 2201 patients, mean (standard deviation [SD]) age was 60.9 (10.9) years, 1019 (46.3%) were female, 1750 (79.5%) were White, 172 (7.8%) were Hispanic, 964 (43.8%) experienced reduced RDI, and 1156 (52.5%) had severe adverse events. Compared to males, females were at significantly higher risks of experiencing reduced RDI (OR [95% CI]: 1.57 [1.27-1.93], P <0.001) and severe AE (OR [95% CI]: 1.73 [1.41-2.12], P <0.001). Conclusions: Our findings suggested females are more likely than men to experience reduced RDI and severe AE during colon cancer chemotherapy. Clinical Impact: In the era of precision medicine, sex (as a biological variable) should be considered in optimizing colon cancer chemotherapy to improve completion and reduce toxicities. Clinical trial information: NCT01150045 .

LBA14 Background: CALGB/SWOG 80702 previously showed that the addition of celecoxib to standard adjuvant chemotherapy with FOLFOX did not significantly improve disease-free survival (DFS) in patients with stage III colon cancer. Here, we evaluated the prognostic and predictive value of ctDNA in identifying a subpopulation of patients who may benefit from celecoxib. Methods: In the subset of patients with adequate biospecimens who participated in CALGB/SWOG 80702, a randomized phase III trial of 3 versus 6 months of adjuvant 5-FU, leucovorin, oxaliplatin (FOLFOX) +/- celecoxib, ctDNA assessment was performed using a clinically validated, tumor-informed 16-plex mPCR-NGS assay (Signatera(TM), Natera, Inc.) after surgery and before the start of adjuvant therapy (baseline). The Kaplan-Meier method was used to describe the distribution of survival time based on ctDNA positivity and log-rank testing was performed. Cox proportional hazards models were used to examine unadjusted associations between ctDNA positivity and disease-free (DFS) and overall survival (OS). Two-sided P values equal to or less than 0.05 were considered statistically significant, except for interaction P values (tested with a likelihood ratio). Results: In total, 1,011 of the 2,526 patients who participated in 80702 had ctDNA testing results from baseline; 189 were ctDNA positive (18.7%). ctDNA positivity associated with male sex, higher T stage, and N2 (versus N1) stage. ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR] 6.52 [95% confident interval (CI) 5.09-8.34; p<0.0001] and OS (HR 6.28 [95% CI 4.63-8.51; p<0.0001]). Three-year DFS was 86.6% in ctDNA-negative cases and 36.8% in ctDNA-positive cases. Among patients who were ctDNA negative, celecoxib use was not significantly associated with worse DFS as compared to placebo (HR 0.75 [95% CI 0.54-1.05; p=0.095]) with a three-year DFS of 87.7% versus 85.5%, respectively. Among ctDNA-positive patients, celecoxib significantly improved DFS compared to placebo (HR 0.59 [95% CI 0.42-0.85; p=0.004]) with a three-year DFS of 44.1% versus 26.6% (P interaction = 0.25). Similar results were seen for overall survival with a hazard ratio of 0.86 (95% CI 0.56-1.33; p=0.49) for ctDNA negative cases and 0.63 (95% CI 0.41-0.96; p=0.028) for ctDNA-positive cases for celecoxib versus placebo (P interaction = 0.28). Conclusion: In a randomized phase III adjuvant therapy trial for stage III colon cancer, ctDNA was highly prognostic of DFS and OS. ctDNA positivity also appeared predictive of the benefit of adjuvant celecoxib for DFS and OS. These results suggest a potential role for ctDNA in determining which patients should consider celecoxib in addition to standard FOLFOX adjuvant therapy. Clinical trial information: NCT01150045 .

PURPOSE SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs). METHODS Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m 2 , cisplatin 25 mg/m 2 , and nab-paclitaxel 100 mg/m 2 intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m 2 and cisplatin 25 mg/m 2 intravenously once per day on days 1 and 8 of a 21-day cycle). RESULTS Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC. There was no significant difference in overall survival (OS) between GAP versus GC. Median OS with GAP was 14.0 months (95% CI, 12.4 to 16.1) and 13.6 months with GC (95% CI, 9.7 to 16.6); hazard ratio (HR), 0.91 (95% CI, 0.72 to 1.14); P = .41. Median progression-free survival (PFS) was similar between groups with median PFS for GAP being 7.5 months (95% CI, 6.4 to 8.5) versus 6.3 months for GC (95% CI, 4.4 to 8.2); HR, 0.89 (95% CI, 0.71 to 1.12); P = .32. In exploratory subset analyses, the OS and PFS benefits of GAP versus GC treatment were greater in locally advanced disease compared with metastatic disease, although not statistically significant (interaction P = .14 for OS and P = .17 for PFS). Moreover, GAP versus GC showed greater improvement in PFS among participants with GBC than those with ICC or ECC (interaction P = .01), but not OS (interaction P = .28). CONCLUSION The addition of a taxane in the GAP regimen to the standard gemcitabine-cisplatin regimen did not improve OS in newly diagnosed BTC. More toxicity was encountered with GAP versus GC.

Abstract Background Inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods This cohort study was nested within the Cancer and Leukemia Group B (now part of the Alliance for Clinical Trials in Oncology) and Southwest Oncology Group randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results The 3-year disease-free survival rate was 88.4% among patients with low inflammation and sufficient physical activity (referent group for all comparisons), 84.9% with low inflammation and insufficient physical activity (absolute risk difference = −3.5 percentage points, 95% confidence interval [CI] = −11.3 to 4.3; P = .38), 78.0% with intermediate inflammation and insufficient physical activity (absolute risk difference = −10.4 percentage points, 95% CI = −17.4 to −3.3; P = .007), and 79.7% with high inflammation and insufficient physical activity (absolute risk difference = −8.7 percentage points, 95% CI = −15.7 to −1.6; P = .022). In contrast, the 3-year disease-free survival rate was 87.3% among patients with intermediate inflammation and sufficient physical activity (absolute risk difference = −1.1 percentage points, 95% CI = −7.5 to 5.3; P = .74) and 84.4% with high inflammation and sufficient physical activity (absolute risk difference = −4.0 percentage points, 95% CI = −12.3 to 4.3; P = .34). Conclusion In this observational study of stage III colon cancer patients, physical activity was associated with improved disease-free survival despite high inflammation. Patients with intermediate or high inflammation who were physically active had disease-free survival rates that were not statistically significantly different from those with low inflammation.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Observational studies have associated aspirin or cyclooxygenase 2 (COX-2) inhibitor usage either before or after colorectal cancer diagnosis with lower risk of recurrence and suggest that PIK3CA mutational status is predictive of better response to COX-2 inhibition. To prospectively test whether adding the COX-2 inhibitor celecoxib to standard adjuvant chemotherapy reduces the risk of recurrence and improves survival, the National Cancer Institute sponsored the CALGB/SWOG 80702 trial (ClinicalTrials.gov identifier: NCT01150045 ) for patients with stage III resected colon cancer. Although the primary hypothesis for all patients did not show a statistically significant improvement in disease-free survival (DFS) with celecoxib, subgroup analysis by PIK3CA mutational status was a preplanned study. PIK3CA gain-of-function mutations were detected in 259 of 1,197 tumors with available whole-exome sequencing data. When stratified by PIK3CA status, patients with PIK3CA gain-of-function mutations treated with celecoxib exhibited improved DFS (adjusted hazard ratio [HR], 0.56 [95% CI, 0.33 to 0.96]) compared with PIK3CA wildtype patients (adjusted HR, 0.89 [95% CI, 0.70 to 1.14]), although the interaction test was nonsignificant ( Pinteraction = .13). Overall survival was similarly improved for patients with PIK3CA gain-of-function mutations (adjusted HR, 0.44 [95% CI, 0.22 to 0.85]) compared with PIK3CA wildtype patients (adjusted HR, 0.94 [95% CI, 0.68 to 1.30]; Pinteraction = .04). Although the test for heterogeneity in DFS did not reach statistical significance, the results suggest potential utility of PIK3CA to consider selective usage of COX-2 inhibitors in addition to standard treatment for stage III colon cancer.

LBA490 Background: Biliary tract cancers (BTCs) are a heterogeneous group of malignancies with a dismal prognosis. Gemcitabine-based regimens are the standard of care in advanced disease, but median overall survival (OS) is roughly 12 months. The addition of albumin-bound paclitaxel to gemcitabine and cisplatin (GAP) demonstrated promising efficacy in a 60 patient, single-arm phase II study (Shroff et al, JAMA Oncol 2019), with observed median OS of 19.2 months. Methods: SWOG 1815 is a randomized, open-label, phase III trial comparing GAP to gemcitabine/cisplatin (GC). The study included newly diagnosed advanced BTC patients (pts), randomized 2:1 to GAP vs. GC. GAP included gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2 and albumin-bound paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. GC included standard dosing of gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8 of a 21-day cycle. Pts were treated until progression. The primary endpoint was overall survival (OS) with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025; randomization was stratified by disease site (intrahepatic cholangiocarcinoma [CCA] vs gallbladder adenocarcinoma [GBC] vs extrahepatic CCA), disease stage (locally advanced vs metastatic), and Zubrod PS 0 vs 1. Results: Of 441 eligible pts randomized, 55% were female. 67% of patients had intrahepatic CCA, 16% had GBC and 17% had extrahepatic CCA. Most pts had metastases (73%). Median OS with GAP vs. GC was 14 vs. 12.7 mo respectively (HR 0.93, 95% CI 0.74-1.19, p=0.58), ORR (confirmed and unconfirmed) 34% vs 25% (p=0.11) and median PFS 8.2 vs 6.4 mo (HR 0.92, 95% CI 0.72-1.16, p=0.47), respectively. Grade 3 and 4 treatment related adverse events (TRAEs) in ≥10% of pts for GAP and GC were anemia, neutropenia, and thrombocytopenia. GAP had more ≥ grade 3 hematologic AEs compared to the GC arm (60% vs. 45%, p=0.003). Discontinuation due to toxicity was at 24% vs 19% (p=0.26) with GAP vs GC. In exploratory subset analyses, GAP vs GC improved OS in pts with locally advanced disease (medians 19.2 vs 13.7 mo; HR 0.67, 95% CI 0.42-1.06, p=0.09) and in GBC pts (medians 17.0 vs 9.3 mo; HR 0.74, 95% CI 0.41-1.35, p=0.33). ORR for GAP vs GC in GBC was 50% vs 24% (p=0.09) and for locally advanced disease 28 vs 21% p=0.74. Conclusions: SWOG 1815 did not result in a statistically significant improvement in median OS with GAP vs. GC. The GAP regimen had higher rates of TRAEs without a statistically significant difference in discontinuation rates. Pts with locally advanced disease and GBC may benefit from the use of GAP. Further analyses are ongoing to understand potential benefit of GAP in subsets of BTC pts. Funding: NIH/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, and CA180868; and in part by Celgene Corporation, Summit, NJ (subsidiary of Bristol Myer Squibb). Clinical trial information: NCT#03768414 .