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5374 citation(s) found for "St Louis, E K".

A phase 2 trial of androgen deprivation therapy interruption in patients responding exceptionally to androgen receptor pathway inhibitor in metastatic hormone-sensitive prostate cancer (A-DREAM / Alliance A032101).
Choudhury, Atish D. , Ballman, Karla V., Reimers, Melissa A., Laccetti, Andrew Leonard , Ravi, Praful, Xiao, Han, Dooley, Katharine, Hillman, DW, Gartrell, Benjamin, Steen, Preston D. , Smith, Thomas J., Beltran, H, Chen, Ronald C., Berg, S., McKay, Rana R., Galsky, Matthew D., Rosenberg, Jonathan E., Morris, M J, Choudhury, Atish D , Ballman, K., Reimers, Melissa A. , Smieliauskas, Fabrice , Ravi, Praful , Xiao, Han , Dooley, Katharine , Hillman, David W. , Mazza, Gina L , Gartrell, Benjamin A. , Smith, Thomas J. , McKay, Rana R. , Galsky, Matthew D. , Rosenberg, Jonathan E , Morris, Michael J.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 5004-5004

10.1200/jco.2026.44.16_suppl.5004 Get It

5004 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated continuously with testosterone suppression (TS) plus an androgen receptor pathway inhibitor (ARPI) can experience cumulative toxicity. We conducted this single-arm phase 2 trial (NCT05241860) to test the hypothesis that pts who achieve favorable response to TS + ARPI can have prolonged treatment-free interval with testosterone recovery after treatment interruption (TI). Here we report on the primary endpoint. Methods: Eligible pts had mHSPC by conventional imaging with prostate-specific antigen (PSA) ≥ 5 ng/ml and testosterone ≥ 150 ng/dl prior to starting TS+ARPI, with PSA < 0.2 ng/ml and testosterone < 50 ng/dl at the time of enrollment after having received TS for 540-750 days and ARPI for ≥ 360 days. Prior local therapy, radiation to metastases and docetaxel were permitted. After enrollment, pts discontinued TS and ARPI and were followed with PSA and testosterone levels every 3 months (mo), CT/MRI and bone scan at least every 6 mo, and FACT-P questionnaire for patient-reported outcomes (PROs) every 6 mo. Treatment was resumed for PSA ≥ 5 ng/ml, radiographic change (progressive disease [PD] per RECIST 1.1 on CT/MRI or unconfirmed PD per PCWG3 on bone scan), or prostate cancer-related symptoms. The primary endpoint was proportion of men remaining treatment-free 18 mo after TI with eugonadal testosterone ( > 150 ng/dl). Target enrollment was 75 pts to differentiate 18-mo treatment-free rates of 0.30 (H 0 ) and 0.45 (H a ). Results: Of 79 pts enrolled between 07/2022 and 03/2024, 78 were eligible and underwent TI. Among these 78, median PSA prior to starting TS+ARPI was 19 (range 5-6759), 27 (35%) had high volume disease, 31 (40%) never received local therapy, and 55 (71%) did not receive radiation to metastases. By 18 mo after TI, 67% (52/78) recovered testosterone and 58% (45/78) remained treatment-free; 41% (32/78) remained treatment-free with testosterone recovery (80% CI 33.5-48.9%, one-sided p 0.0249). At median follow-up of 21.2 mo, 35% (27/78) resumed initial TS+ARPI after meeting re-initiation criteria (of whom 1 required treatment switch for PD 9 mo later); 5% (4/78) resumed prior to meeting criteria; 9% (7/78) pursued alternative therapy instead of resuming TS+ARPI per protocol; 5% (4/78) withdrew; 1 died of myocardial infarction prior to resuming treatment. 4 pts died, 1 of prostate cancer. Conclusions: The primary objective was achieved with 41% of favorable responders to TS+ARPI remaining treatment-free with testosterone recovery at 18 mo after TI. Analyses of biomarkers and PROs are in progress, and pts will be followed for long-term outcomes. Support: U10CA180821, U10CA180882, UG1CA189823, https://acknowledgments.alliancefound.org, Veracyte Inc. Clinical trial information: NCT05241860 .
MAIN-CAV: Phase III randomized trial of maintenance cabozantinib and avelumab versus avelumab after first-line platinum-based chemotherapy (PBC) in patients (pts) with locally advanced/metastatic urothelial cancer (la/mUC; Alliance A032001).
Gupta, S, Sridhar, Srikala S., Chen, Ronald C., Chan, Timothy An-thy, Wen, Yujia , Berg, S., Yen, Aihua Edward, Baghaie, Shiva, Singh, Parminder, Reimers, Melissa A., Morris, M J, Galsky, Matthew D., Rosenberg, Jonathan E., Gupta, Shilpa , Ballman, Karla V. , Apolo, Andrea B , Sridhar, Srikala S , Chan, Timothy An-thy, Singh, Parminder Pal , Reimers, Melissa A. , Morris, Michael J. , Rosenberg, Jonathan E

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4514-4514

10.1200/jco.2026.44.16_suppl.4514 Get It

4514 Background: Maintenance avelumab is a standard of care in patients (pts) with la/mUC who do not progress after first-line PBC. Cabozantinib (CABO) is an oral inhibitor of MET, VEGFR and TAM, active in multiple solid tumors. We hypothesized that an avelumab (Av)-CABO combination would improve outcomes in pts with mUC with an acceptable safety profile compared to avelumab maintenance alone. Methods: MAIN-CAV (NCT05092958) is a phase III randomized, multicenter, international trial for la/mUC pts who did not progress after 4-6 cycles of any PBC (gemcitabine-cisplatin, gemcitabine-carboplatin, MVAC, ddMVAC). Pts were randomized 1:1 to Av 800 mg IV every 2 weeks alone or with CABO 40 mg daily for ≤2 years. Stratification factors were response to first-line PBC (complete response [CR] vs partial response [PR] vs stable disease [SD]) and visceral metastases. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), safety and quality of life. The target accrual was 654 pts; the trial closed early after enrollment of 68 pts following adoption of enfortumab vedotin plus pembrolizumab as the new preferred first-line standard in the US. Results: From 3/2022 to 3/2024, 68 pts were randomized (Av n = 33; CABO-Av n = 35). Median OS was 24.8 months (mo) with Av and 23.0 mo with Avb-CABO (Hazard ratio 1.41; 95% CI 0.66–3.01; p = 0.186). Median PFS was 4.6 mo with Av vs 6.0 mo with Av-CABO (p = 0.343). Objective response rate among pts with PR or SD after first-line PBC was 20.8% with Av vs 11.5% with Av-CABO (p = 0.424). Grade ≥3 treatment-related adverse events occurred in 24.2% pts on the Av arm vs 39.4% of pts on the Av-CABO arm and CABO dose reductions occurred in 63% of pts. Conclusions: Addition of CABO to Av did not improve OS or PFS compared with Av alone in this underpowered, prematurely closed phase III trial; safety was consistent with known profiles. U10CA180821,U10CA180882; U24CA196171, U10CA180863. (CCTG);U10CA180888 (SWOG); https://acknowledgments.alliancefound.org. Clinical trial information: NCT05092958 .
Effect of on-treatment dose adjustments on the efficacy of enfortumab vedotin and pembrolizumab (EVP) in advanced urothelial carcinoma (aUC): A UNITE analysis.
Zhong, Jeffrey Yinhong, Thomas, Zachariah, Bakaloudi, Dimitra, Jaime-Casas, Salvador, Tripathi, Abhishek, Grivas, Petros, Campbell, M, Reimers, Melissa A., P, Fu, Koshkin, Vadim S. , Zhong, Jeffrey Yinhong , Jang, Albert, Jindal, Tanya , Jiang, Cindy Y. , Thomas, Zachariah, Oh, Eugene, Nguyen, Charles B. , Jaime‐Casas, Salvador , Tripathi, Abhishek , Grivas, Petros , Tsung, Irene , Campbell, Matthew T. , Alhalabi, Omar , Reimers, Melissa A. , Khaki, Ali Raza , Chen, Zhengyi , Brown, Jason R.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4565-4565

10.1200/jco.2026.44.16_suppl.4565 Get It

4565 Background: EVP is the preferred 1 st -line regimen for patients (pts) with aUC. EV-related toxicities are often managed with dose adjustments, such as reductions and holds. Analysis of EV monotherapy trials showed consistent survival outcomes despite dose adjustments. We hypothesized that on-treatment EV dose adjustments would not impact survival in these pts. Methods: Pts with aUC treated with EVP in the multisite UNITE study were analyzed. Early dose reductions (DR) and holds were defined as occurring < 9 weeks from EVP start, with the remainder classified as late. Pts with DR at treatment start were excluded. Survival endpoints were progression-free survival (PFS) and overall survival (OS) from EVP start, assessed by Kaplan-Meier analysis and Cox models. Multivariable Cox analysis (MVA) included age (≥ 75 vs < 75), ECOG performance status (0-1 vs 2-3), Hgb level (< 10 vs ≥ 10) and liver metastases (present vs not). A time-dependent covariate was used to reduce immortal time bias. Complementary MVA landmark analyses were performed, aligned to the total number of treatment cycles received, with six analyses from cycles 2 to 7. Results: 360 pts from 17 sites were included (median age 70; 78% Caucasian; 76% male; 27% upper tract primary; 35% histology subtype component; 17% with liver metastasis; 78% frontline); median follow-up was 11.7 months (95% CI [10.79, 13.08]). Median number of cycles was 6 in pts with DR and 3 with no DR. Early DRs (100 pts [28%]) and holds (18 pts [5%]) were most commonly due to rash (28% of all early DRs and holds). Late DR (75 pts [21%]) and holds (50 pts [14%]) were most commonly due to neuropathy (52% of all late DRs and holds). Pts with early or late DR had longer PFS and OS vs those who did not (Table); however, there was no significant PFS or OS difference with dose hold vs no hold (PFS HR 0.65, 95%CI (0.40, 1.05), p = 0.08; OS HR 0.70, 95%CI (0.39, 1.27), p=0.24). In landmark analyses, about 50% of pts had DR; no significant difference in PFS or OS was observed at most landmarks, except for longer OS in the DR cohort at cycle 4 (HR 0.53, 95% CI (0.29, 0.98), p = 0.042) and cycle 5 (HR 0.43, 95% CI (0.19, 0.99), p = 0.048). Conclusions: In this real-world retrospective analysis, EVP efficacy was maintained despite DR and dose holds. Survival difference noted in the time-dependent analyses were not consistently reproduced in landmark analyses, suggesting exposure-related selection bias rather than causal effect. Prospective studies are warranted to validate these hypothesis-generating findings. Association of EV DR with PFS/OS (time-dependent analyses). Early DR Late DR DR vs no DR outcomes UVAHR (95% CI), p MVAHR (95% CI), p UVAHR (95% CI), p MVAHR (95% CI), p PFS 0.50 (0.35, 0.72), <.001 0.56 (0.38, 0.84), 0.005 0.32 (0.21, 0.49), <.001 0.36 (0.23, 0.57), <.001 OS 0.51 (0.32, 0.79), 0.003 0.57 (0.35, 0.92), 0.022 0.26 (0.15, 0.45), <.001 0.31 (0.17, 0.55), <.001
Cabozantinib in high-grade neuroendocrine neoplasms.
Trikalinos, Nikolaos, Firwana, Belal, Reimers, Melissa A., Mehan, Paul, Rohatgi, Anjali , Pressey, Olive, Waldron, Nicholas, Wu, Shuang , Tan, Benjamin , Suresh, Rama , Pedersen, Katrina S. , Firwana, Belal , Reimers, Melissa A. , Liu, Jingxia

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4183-4183

10.1200/jco.2026.44.16_suppl.4183 Get It

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 .
Efficacy and safety of cabozantinib (CABO) in advanced neuroendocrine tumors (NET) according to hormone functional status: Subgroup analysis of phase 3 CABINET trial (Alliance A021602).
Trikalinos, Nikolaos, Geyer, Susan Michelle, Zemla, Tyler, Strosberg, Jonathan R., Wolin, Edward M., Halfdanarson, Thorvardur Ragnar, Knopp, M.V., Behr, MD Spencer, Shergill, Ardaman , Raj, Nitya , Shaheen, Shagufta, Vijayvergia, Namrata , Dasari, Arvind, O'Reilly, Eileen M., Meyerhardt, Jeffrey A., Chan, Jennifer A., Shaheen, Shagufta , Zemla, Tyler , Strosberg, Jonathan , Wolin, Edward M. , Hálfdánarson, Þorvarður R. , Konda, Bhavana , Ou, Fang‐Shu , Acoba, Jared David , Tawfik, Bernard , Dasari, Arvind , O’Reilly, Eileen M. , Meyerhardt, Jeffrey A. , Chan, Jennifer A.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4178-4178

10.1200/jco.2026.44.16_suppl.4178 Get It

4178 Background: In the CABINET trial, CABO significantly prolonged progression-free survival (PFS) compared to placebo (PB) in patients (pts) with advanced, previously treated extrapancreatic NET (epNET) or pancreatic NET (pNET) (Chan et al., NEJM, 2025). Here we report outcomes according to functional status based on NET hormone secretion. Methods: Pts with locally advanced or metastatic epNET or pNET were randomized 2:1 in separate cohorts to receive CABO 60 mg daily vs PB. Eligibility included progression by RECIST within 12 months (mo) before registration, ≥ 1 prior systemic therapy not including somatostatin analogs (SSA). Pts with functional NET due to hormone secretion and non-functional NET were included. In this post hoc subgroup analysis, we analyzed PFS by blinded independent central review and adverse events for pts receiving CABO vs PB based on functional status. Cox regression models were used with stratification on primary tumor site (epNET vs pNET). Subset analyses to evaluate treatment arm differences were conducted in pts with functional and non-functional tumors. Due to small numbers, separate results for those with unknown functional status are not included. Results: Of the total 298 pts enrolled in both cohorts, 74 had a functional NET (CABO, n = 47; PB, n = 27); 179 had a non-functional NET (CABO, n = 123; PB, n = 56); 45 had unknown functional status (CABO, n = 28; PB, n = 17). For functional NET, primary tumor sites were GI tract (n = 50; 68%), pancreas (n = 15; 20%), unknown (n = 4; 5%), lung (n = 3; 4%), and thymus (n = 2; 3%). Secreted hormones that were reported included serotonin (55%), somatostatin (18%), gastrin (16%), glucagon (4%), insulin (4%), ACTH (1%), and vasoactive intestinal peptide (1%). For non-functional NET, primary tumor sites were pancreas (n = 75; 42%), GI tract (n = 42; 23%), lung (n = 30; 17%), unknown (n = 17; 9%), thymus (n = 8; 4%), and other (n = 7; 4%). Concurrent SSA was received by 91% and 53% of pts with functional and non-functional NET, respectively. In both subgroups, CABO was associated with improved PFS compared to PB (for functional NET: stratified hazard ratio [sHR], 0.40; 95% confidence interval [CI]: 0.20-0.82, P = 0.012; for non-functional NET: sHR, 0.26; 95% CI: 0.17-0.41, P < 0.001). The most frequent grade 3/4 adverse events (AEs) attributed to CABO vs PB in pts with functional NET included hypertension (21% vs 11%), diarrhea (9% vs 11%), and fatigue (2% vs 15%); in pts with non-functional NET, grade 3/4 AEs included hypertension (21% vs 4%) and fatigue (18% vs 4%). Conclusions: Subset analyses of the CABINET trial suggest that CABO is an effective treatment option for pts with functional and non-functional epNET or pNET. Efficacy and safety results for pts with functional or non-functional NET treated with CABO are consistent with results for the entire trial. Clinical trial information: NCT03375320 .
Cohort-level safety and efficacy results for [ 212 Pb]VMT-α-NET in advanced somatostatin receptor subtype 2 (SSTR2+)–expressing neuroendocrine tumors (NETs): Cohorts 1–3.
Halfdanarson, Thorvardur Ragnar, Sukrithan, Vineeth, Mancini, Brandon Robert, Mosallaie, Seyed Ali, Balaraman, Savitha, Sibley, Gregory, Starr, Jason S., Anthony, Lowell , Liao, Chih-Yi, Mehr, Samuel, Weiss, J., Ramirez, Robert A., Iravani, Amir Iravani, Baratto, Lucia, Yang, Wenjing, Hanna, Alaa , Keefe, Stephen Michael, Puhlmann, Markus , Prasad, Vikas, Hálfdánarson, Þorvarður R. , Wahl, Richard L. , Sukrithan, Vineeth , Sibley, Gregory S., Starr, Jason S. , Liao, Chih‐Yi , Mehr, Samuel H., Weiss, Jared, Ramirez, Robert A., Keefe, MD Stephen, Prasad, Vikas

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4173-4173

10.1200/jco.2026.44.16_suppl.4173 Get It

4173 Background: [ 212 Pb]VMT-α-NET is an alpha-particle radiation-delivering agent targeted to somatostatin receptor type 2 (SSTR2)-expressing tumors. Here, we present safety and efficacy results from the dose-finding phase 1/2a clinical trial (NCT05636618). Methods: This phase 1/2a dose-escalation study uses a Bayesian algorithm to identify an optimal dose of [ 212 Pb]VMT-α-NET for participants with advanced, well-differentiated NETs expressing SSTR2. Eligible participants must have unresectable or metastatic disease, documented radiologic progression following at least one prior systemic treatment, and evidence of SSTR2 expression (Krenning Score ³2) in ≥1 lesion confirmed on an FDA-approved somatostatin receptor PET scan. Patients previously treated with systemic peptide receptor radionuclide therapy (PRRT) are excluded from enrollment. During the dose-finding phase, participants may receive up to four administrations of [ 212 Pb]VMT-α-NET at their assigned dose level, and they are monitored for dose-limiting toxicities (DLTs) for 42 days and safety throughout the study. Efficacy is evaluated by investigators according to RECIST criteria v1.1. Dosimetry is included as a supportive analysis. Results: As of the 10-Dec-2025 data cut-off (DCO), 56 participants had been enrolled across Cohorts 1, 2, and 3 and received at least one dose of [ 212 Pb]VMT-α-NET: 2 participants in Cohort 1 (2.5 mCi), 46 in Cohort 2 (5 mCi), and 8 in Cohort 3 (6 mCi). No dose-limiting toxicities, grade 5 adverse events, treatment-related discontinuations, serious renal events, dysphagia, or clinically meaningful treatment-related myelosuppression were observed. The median follow-up for all treated participants was 40 weeks (range 6–97). Efficacy has been summarized in this abstract for 25 participants (2 in Cohort 1 and 23 in Cohort 2). Nineteen of these 25 participants remained progression-free at the time of the DCO, with a median efficacy follow-up of 49 weeks (range 6–97). In Cohort 2, investigators observed RECIST v1.1 objective responses in 9 of 23 participants (39%), including 8 confirmed responses. Both participants in Cohort 1 continued to exhibit stable disease after two years of follow-up. Updated safety for all participants and updated efficacy for participants with sufficient maturity beyond the 25 summarized here will be presented at the congress. Conclusions: Treatment with [ 212 Pb]VMT-α-NET continues to demonstrate a favorable safety profile across all treated participants (n = 56) and shows signs of sustained efficacy at the 2.5 mCi and 5 mCi dose levels. The therapy has been well-tolerated with no observed dose-limiting toxicities or serious treatment-related adverse outcomes. Based on these encouraging safety and efficacy findings, the study is ongoing, and enrollment into Cohort 3 (6 mCi) remains active. Clinical trial information: NCT05636618 .
Final results of a phase II study of fluorouracil (FU), leucovorin (LV), and nanoliposomal irinotecan (nal-IRI) in previously treated biliary tract cancer (NAPOLI-2).
Tan, Benjamin R., Turk, Anita, Sung, Max W. , Aranha, Olivia, Mukherji, Reetu , Noel, Marcus Smith , Lim, Kian-Huat, Khushman, M., Trikalinos, Nikolaos, Marshall, John, Wang, Hongkun, Weinberg, Benjamin A. , Tan, Benjamin , He, Aiwu Ruth , Aranha, Olivia , Ratner, Lee , Suresh, Rama , Lim, Kian-Huat, Marshall, John L , Pedersen, Katrina S.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 4122-4122

10.1200/jco.2026.44.16_suppl.4122 Get It

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 .
Phase 3 study (APROMISS) of catequentinib hydrochloride (AL3818) monotherapy in patients with advanced alveolar soft part sarcoma (ASPS).
Trent, Jonathan C., Somaiah, Neeta , Chugh, Rashmi, Fan, Zhengfu, Jones, Robin Lewis, Tine, Brian Andrew Van, Bui, Nam, Chawla, Sant P. , Shen, Zan, Vincenzi, Bruno, Keedy, Vicki L. , Bui, Nam Q. , Bui, Nam , Stacchiotti, Silvia , Trent, Jonathan C. , Chmielowski, Bartosz , Chugh, Rashmi , Jones, Robin Lewis, Burgess, Melissa , Vincenzi, Bruno , Pollack, Seth M. , Siontis, Brittany L.

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 11502-11502

10.1200/jco.2026.44.16_suppl.11502 Get It

11502 Background: To report results from the open-label alveolar soft part sarcoma (ASPS) cohort of the phase III APROMISS trial (NCT03016819) evaluating Catequentinib hydrochloride (AL3818), an oral multitargeted receptor tyrosine kinase inhibitor, in adults with advanced or metastatic ASPS. Methods: Adult patients with pathologic and molecularly confirmed advanced ASPS, either treatment-naive or previously treated (excluding cediranib), were enrolled in the open-label, non-randomized ASPS cohort of the phase III APROMISS trial conducted across the United States, Asia, and Europe. Catequentinib hydrochloride was administered orally at 12 mg once daily in 21-day cycles (14 days on/7 days off) until disease progression, toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per RECIST by Blinded Independent Central Review (BICR) (predefined threshold: 31%). Secondary endpoints included duration of response (DOR) with a predefined target of =/>6 months, progression free survival (PFS) and overall survival (OS). Results: From July 2017 to August 2022, a total of 56 patients entered the trial; 56 patients were evaluable for the primary endpoint. Median (m-) age was 29.5 years (range: 18 – 66), with 24 female and 32 male. Best overall response included 1/56 complete response (1.8%), 14/56 partial responses (25.0%), 36/56 stable disease (64.3%), and 3/56 (5.4%) progressive disease. RECIST ORR by BICR was 26.8% (95% CI, 15.8–40.3); m-DOR was 22.57 months (95%CI: 10.38-NE). The study data was collected close to 8 years for all patients. mPFS was 18.33 months (95% CI, 14.19–23.13), with 6- and 12-month progression-free rates of 88.77% (95% CI, 76.68–94.79) and 65.54% (95% CI, 50.42–77.06), respectively. mOS was 59.27 months (95% CI, 44.09–NE), with 6- and 12-month overall survival rates of 94.64% (95% CI, 84.30–98.24) and 90.81% (95% CI, 79.30–96.08), respectively. Overall, 27/56 (48.2%) patients experienced grade ≥3 treatment-related adverse events, most commonly diarrhea (50.0%), hypertension (44.6%), fatigue (37.5%), nausea (35.7%), and palmar-plantar erythrodysesthesia syndrome (30.4%); one patient (1.8%) had a grade 5 event (respiratory failure). Conclusions: Catequentinib hydrochloride demonstrated meaningful antitumor activity and durable responses in adults with advanced ASPS. Despite the ORR of 26.8% slightly below the predefined 31% threshold, disease control was prolonged, with a m-DOR exceeding 22 months. Favorable PFS and OS outcomes, together with a manageable safety profile, support its clinical benefit in this ultra-rare sarcoma. Clinical trial information: NCT03016819 .
Enhanced financial assistance intervention for unmet essential needs: A prospective pilot study to improve timely cancer treatment completion.
Jiang, Shannon Jinxia, Johnson, Kimberly J., Yang, Joanna C. , Barnes, Justin M. , Johnson, Kimberly J., Chino, Fumiko

Journal of Clinical Oncology | May 27, 2026 | Volume: 44 | Issue: 16_suppl | Pages: 11078-11078

10.1200/jco.2026.44.16_suppl.11078 Get It

11078 Background: Unmet essential needs, such as food, transportation, and housing insecurity, can create barriers to timely cancer treatment. Delayed or prolonged courses of definitive radiotherapy (RT) can compromise cancer outcomes like recurrence and survival. There are limited prospective data testing interventions to improve timely cancer treatment completion by meeting essential needs. Methods: We conducted a pragmatic single-arm pilot study testing an enhanced financial assistance intervention for unmet needs during RT. Eligibility criteria included adults with a cancer diagnosis and unmet social needs (via social risk screening and/or social worker evaluation) who were prescribed or undergoing a course of RT with > 10 fractions remaining. Participants received standard institutional assistance (e.g., limited support for travel/lodging with strict eligibility criteria) plus the enhanced assistance intervention, including needs assessments prior to and during RT and up to $2000/patient of tailored unconditional monetary transfer via gift cards for all essential needs identified. The primary outcome was delay-free completion of RT (DFC: completing all prescribed RT fractions and delaying < 5 fractions). The study was powered (power = 80%, 1-sided alpha = 0.2 for this pilot study) to detect a 10-percentage point increase in % DFC relative to a historic benchmark of 83% (based on similar patients from our institution), with required sample size of N = 33. Due to delays in gift card administration (on average ~2 weeks after consent), we also present per protocol analysis, limited to patients who had > 10 fractions remaining after first receiving financial assistance. Post-hoc analyses using generalized linear mixed models evaluated percentages of delayed fractions prior to and after an individual’s receipt of financial assistance. Results: 35 met inclusion criteria and were approached, 33/35 enrolled. Participants received median assistance of $1800 ($700-2000) and had a median of 27 RT fractions after consent (range: 12-35) and 17 (3-34) after receiving assistance. In the overall cohort, 1 patient did not complete RT and 2 patients had ≥5 delayed fractions, leading to 30/33 achieving DFC (90.9%, 80% CI = 83.9 – 100), significantly higher than the 83% benchmark. In the per protocol analysis, 27/28 achieved DFC (96.4%, 80% CI = 89.7–100, P = .037). Among the 27 patients who started RT prior to receiving assistance, mixed model analysis showed more delayed fractions prior to (7.1%) vs. after (3.0%) receiving assistance (OR 2.84, 95% CI = 1.43-5.80, P = .003). Conclusions: In this prospective pilot study, a tailored enhanced financial assistance intervention for unmet essential needs led to improved delay-free completion of RT over a historic benchmark. Further analysis on patient-reported quality of life and financial toxicity will be reported in the future. Clinical trial information: NCT06582849 .
Decompression with or without Duraplasty for Chiari I and Syringomyelia
Limbrick, David D. , Shannon, Chevis N., Bayman, Emine O., Meehan, Thanda, Kallem, Marisa, Ackerman, Laurie L. , Adelson, P. David , Albert, Gregory, Aldana, Philipp R. , Alden, Tord D. , Anderson, Richard C. E. , Baird, Lissa C., Bauer, David, Bethel-Anderson, Tammy, Bierbrauer, Karin, Brockmeyer, Douglas L. , Chern, Joshua J. , Couture, Daniel, Daniels, David J., Dauser, Robert C., Durham, Susan, Ellenbogen, Richard G., Eskandari, Ramin, Gannon, Stephen R., Grant, Gerald A., Greene, Stephanie, Gross, Naina L. , Guillaume, Daniel J. (Daniel James), Hankinson, T., Heuer, Gregory, Iantosca, Mark, Iskandar, Bermans J. , Jackson, Eric M., Keating, Robert F., Kelly, Michael P., Kennedy, Elaine, Krieger, Mark D., Kulkarni, Abhaya V., Labuda, Rick, Leonard, Jeffrey R., Maher, Cormac O. , Mangano, Francesco T. , McComb, J. Gordon, McEvoy, Sean D., Niazi, Toba N., Oakes, Jerry, Olavarria, Greg, O’Neill, Brent R., Poppe, Dorothy, Ragheb, John, Reynolds, Lisa, Selden, Nathan R., Shah, Manish N., Smyth, Matthew D., Spears, Sandy, Stone, Scellig , Strahle, Jennifer M., Tamber, M, Tramelli, Gina, Tuite, Gerald F. , Vance, Haley, Wait, Scott D. , Wellons, John C. , Whitehead, WE, Yahanda, Alexander T., Yan, Yan, Dacey, Ralph G. , Park, Tae Sung, Torner, James C., Kelly, Michael P. , Torner, James C. , Dlouhy, Brian J , Iskandar, Bermans J , Yahanda, Alexander T , Kelly, Michael P , Limbrick, David D. , Bayman, Emine O. , Ahmed, Raheel , Albert, Gregory W. , Bierbrauer, Karin S. , Daniels, David J. , Ellenbogen, Richard G., Graupman, Patrick C. , Greenberg, Jacob K , Greenfield, Jeffrey P. , Guillaume, Daniel, Iantosca, Mark, Jackson, Eric M., Jallo, George I. , Johnston, James M. , Keating, Robert F., Kennedy, Elaine, Kulkarni, Abhaya V. , McComb, J. Gordon , McKinstry, Robert C. , Menezes, Arnold H. , Poppe, Dorothy , Ragheb, John , Reeves, Samuel, Reynolds, Lisa, Selden, Nathan R. W. , Shah, Manish N. , Shimony, Joshua S. , Strahle, Jennifer M. , Tamber, Mandeep S. , Tyler‐Kabara, Elizabeth C. , Vance, E. Haley, Yahanda, Alexander T. , Park, Tae Sung

New England Journal of Medicine | May 27, 2026 | Volume: 394 | Issue: 20 | Pages: 2015-2025

10.1056/nejmoa2402821 | PMID 42202320 Get It