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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2021
    In:  Critical Reviews in Oncology/Hematology Vol. 168 ( 2021-12), p. 103535-
    In: Critical Reviews in Oncology/Hematology, Elsevier BV, Vol. 168 ( 2021-12), p. 103535-
    Type of Medium: Online Resource
    ISSN: 1040-8428
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 605680-5
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  • 2
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2024
    In:  Journal of Clinical Oncology Vol. 42, No. 3_suppl ( 2024-01-20), p. TPS429-TPS429
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 3_suppl ( 2024-01-20), p. TPS429-TPS429
    Abstract: TPS429 Background: Claudin 18 isoform 2 (CLDN18.2) belongs to a family of tight junction proteins with broad expression in gastric and gastroesophageal junction (GEJ), pancreatic, esophageal, and other solid tumors. Expression of CLDN18.2 in normal tissue is limited to the gastric mucosa, making it a promising antibody-drug conjugate (ADC) therapeutic target. Currently, there are no approved therapies targeting CLDN18.2. EO-3021 (also known as SYSA1801) is an ADC comprised of a fully human CLDN18.2 monoclonal antibody (mAb) specifically conjugated at glutamine 295 with a cleavable linker and MMAE with a homogenous drug-to-antibody ratio (DAR) of 2. In preclinical models, EO-3021 selectively delivers a potent cytotoxic MMAE payload directly to cancer cells expressing CLDN18.2, retains antibody-dependent cellular toxicity (ADCC) and complement-dependent cytotoxicity (CDC) activity, and exhibits a bystander effect. 1 In an ongoing Phase 1 study in China (NCT05009966), EO-3021 exhibited signs of anti-tumor activity in patients with gastric cancer and had an acceptable safety profile. 2 Outside of Greater China, EO-3021 is being evaluated by Elevation Oncology for the treatment of patients with advanced or metastatic solid tumors likely to express CLDN18.2, particularly gastric and GEJ adenocarcinomas. Methods: This is a Phase I, open-label, multi-center, dose escalation and expansion study to investigate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of EO-3021 in patients with solid tumors likely to express CLDN18.2 (NCT05980416). Patients whose tumors have progressed on or after standard therapy, or who are intolerable for available standard therapy are eligible for participation. Approximately 120 patients will be enrolled in this study. There are 4 planned dose levels in the dose finding portion of the study. Patients will receive EO-3021 intravenously (IV) once every three weeks until disease progression or unacceptable toxicity. The expansion cohort will evaluate EO-3021 in patients with gastric/GEJ adenocarcinoma. Provision of tumor samples (archived and fresh biopsy) is required for study enrollment. CLDN18.2 expression in tumor tissue via will be assessed by retrospective evaluation via central immunohistochemistry assay; results will be explored for possible correlation with tumor response. Enrollment in the dose escalation portion of the study began in August 2023. 1. Dan M, et al. Cancer Res. 83, 2023. 2. Wang Y, et al. J Clin Oncol. 41, 2023. Clinical trial information: NCT05980416 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 668-668
    Abstract: 668 Background: We investigated the impact of distance traveled to a tertiary care center for treatment in the management and outcomes of patients with pancreatic adenocarcinoma (PDAC). Methods: Patients treated for operable PDAC at a single institution from 2010-2019 were retrospectively reviewed. Data was collected on demographics, tumor characteristics, social determinants of health, diagnostic/staging work-up, surgical details, and outcomes. Patients were divided into three groups based on distance from our institution: Group A, 〈 10 miles, Group B, 〉 11-50 miles, or Group C, 〉 50 miles. The primary outcome was two-year survival. Results: There were 314 patients included. The mean age was 67.6+10.5 years. Patients farther from the hospital were less likely to undergo CT with contrast (Group B 97.1% versus Group C 89.0%, p = 0.02) and more likely to get MRCP (Group A 17.0% versus Group C 36.3%, p = 0.01) for staging. Distance was also associated with increased time to first encounter with medical or surgical oncology (Group A 6 days versus Group C 9 days, p = 0.02) and treatment initiation (Group A 22 days versus Group C 28 days, p 〈 0.001). There were no differences in postoperative complications, length of stay, discharge disposition, or follow-up. Two-year survival was better in Group A than Group B (54.1% versus 35.5%, p = 0.04). There was no difference in five-year survival. In the multivariable model for two-year survival, no patient or tumor characteristics were significant. Conclusions: In this PDAC population, patients living farther from a tertiary cancer center had worse two-year postoperative survival. Prospective studies in this area are needed.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. 5-5
    Abstract: 5 Background: A growing body of evidence supports the utility of circulating tumor DNA (ctDNA) as a useful biomarker for detecting molecular residual disease (MRD) in colorectal cancer (CRC). Immediately after surgery or during adjuvant therapy, high levels of cell-free DNA (cfDNA) from normal tissue may limit the detection of tumor-derived ctDNA. The optimal timing of blood collection for reliable MRD detection after surgery or adjuvant therapy remains unclear. Methods: In this retrospective, U.S.-based, multi-institutional study, data from commercial ctDNA testing in 16,347 patients with stage I-III CRC were analyzed. Complete clinical data were available for 417 patients with 2,538 plasma samples collected between 6/2019 and 4/2022. The median follow-up for relapsed and non-relapsed patients was 730 and 615 days, respectively. A personalized, tumor-informed multiplex PCR-based next-generation sequencing assay (Signatera) was used to quantify ctDNA prior to surgery and postoperatively in a longitudinal manner. We analyzed the kinetics of total cfDNA and compared it with the ctDNA MRD positivity rates at various time points after surgery. Results: Among all patients, cfDNA levels were higher immediately after surgery (0-2 weeks) and gradually declined during the subsequent 2-8 weeks (p 〈 0.0001). Despite the higher cfDNA levels, among patients with immediate post-operative draws (0-2 weeks) 30.6% (113/369) of patients were ctDNA positive. Similar ctDNA detection rates were observed with conventional MRD windows after resection, whether the window was defined as 2-6 weeks (20.8%; 957/4605) or 2-8 weeks (20.9%; 1155/5534). In the clinically annotated cohort, ctDNA-positivity during the MRD time window of 2-8 weeks and during surveillance ( 〉 6 months post-operatively and subsequent to any adjuvant therapy) was significantly associated with worse recurrence-free survival as compared to ctDNA negative patients (MRD: HR 14.1, 95% CI: 5.8-34; p 〈 0.0001; and surveillance HR 20.6, 95% CI: 10.6-37.6; p 〈 0.0001), respectively. On analyzing cfDNA dynamics during adjuvant therapy, cfDNA levels gradually increased between 8 weeks and 8 months after surgery (p=0.0001), suggesting a potential impact of treatment on cell death and cfDNA shed. Conclusions: This is one of the first, large-scale in-depth studies evaluating treatment-based fluctuations in post-operative cfDNA and its correlation with ctDNA-positivity. Our analyses demonstrated no significant impact of plasma cfDNA levels on ctDNA detection rates across different MRD windows using a tumor-informed approach. This may affect real-world application of personalized ctDNA testing by allowing earlier testing windows, as well as guide clinical trial designs using ctDNA as an integral biomarker.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 4_suppl ( 2023-02-01), p. LBA661-LBA661
    Abstract: LBA661 Background: Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA and Europe for mPDAC following progression with gemcitabine-based therapy. A phase 1/2 study (Wainberg et al. Eur J Cancer 2021;151:14–24; NCT02551991) demonstrated promising anti-tumor activity in patients with mPDAC who received first-line liposomal irinotecan 50 mg/m 2 + 5-FU 2400 mg/m 2 + LV 400 mg/m 2 + oxaliplatin 60 mg/m 2 (NALIRIFOX). Herein, we present results from NAPOLI-3 (NCT04083235), a randomized, open-label, phase 3 study investigating the efficacy and safety of NALIRIFOX compared with nab-paclitaxel + gemcitabine as first-line therapy in patients with mPDAC. Methods: Eligible patients with histopathologically/cytologically confirmed untreated metastatic PDAC were randomized (1:1) to receive NALIRIFOX on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m 2 + gemcitabine 1000 mg/m 2 (Gem+NabP) on days 1, 8 and 15 of a 28-day cycle. Randomization was stratified by ECOG performance status, geographic region and presence or absence of liver metastases. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate (ORR) and safety. OS was evaluated when ≥ 543 events were observed using a stratified log-rank test with an overall 1-sided significance level of 0.025. Results: Overall, 770 patients (NALIRIFOX, n = 383; Gem+NabP, n = 387) were included. Baseline characteristics were well balanced between arms. At a median follow-up of 16.1 months, 544 events had occurred. The median OS was 11.1 months in the NALIFIROX arm as compared with 9.2 months in the Gem+NabP arm (HR 0.84 [95% CI 0.71–0.99]; p = 0.04); PFS was also significantly improved (7.4 months vs 5.6 months; HR 0.70 [0.59–0.84] ; p = 0.0001). Grade 3/4 treatment-emergent adverse events (TEAEs) with ≥ 10% frequency in patients receiving NALIRIFOX versus Gem+NabP included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (14.1% vs 24.5%). Conclusions: First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in treatment-naïve patients with mPDAC. The safety profile of NALIRIFOX was manageable and consistent with the profiles of the treatment components. Funding: Funded by Ipsen. Clinical trial information: NCT04083235 .[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 438-438
    Abstract: 438 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy and treatment beyond first-line platinum doublet remains largely investigational. The immunomodulatory properties of conventional cytotoxic therapy, particularly in regard to the upregulation of PD-L1 expression rendering tumor cells less sensitive to T cell-mediated lysis, rapid emergence of chemotherapy resistance, and known modest efficacy of single agent anti-PD-1 antibody in BTC provide a rationale for combination chemoimmunotherapy. We conducted a multi-center, phase Ib/II, single-arm study to investigate the role of liposomal-irinotecan, 5FU and LV in combination with nivolumab as second-line therapy in pts with advanced BTC. Methods: Key eligibility criteria include histologically confirmed unresectable or metastatic BTC after progression or intolerance of first-line systemic therapy, measurable disease per RECISTv1.1, ECOG PS 0-1, and absence of autoimmune disease or chronic steroid use. The limited phase Ib portion evaluated 10 pts to determine the recommended phase 2 dose (RP2D) based on the probability of dose-limiting toxicity (DLT) rate 〈 30% during days 1-29. Study treatment included 5FU 2400 mg/m 2 over 46 hrs, LV 400 mg/m 2 , liposomal-irinotecan 70 mg/m 2 at dose level 0 along with nivolumab 240 mg every 2 wks for up to 2 yrs in absence of disease progression or unacceptable toxicity. The primary endpoint was median progression-free survival (PFS) rate with an alternative and null hypothesis of 5.0 mo and 2.9 mo (two-sided alpha 0.05, power 80%), respectively. Secondary endpoints included best overall response rate (ORR) per immune related (ir)RECIST, median overall survival (OS), 75 th percentile estimates of PFS and OS, and safety. Exploratory objectives include biomarker analysis using include targeted panel exome/transcriptome and immune cell subsets in tissue. Results: 30 eligible pts (60% men, 83% Caucasian) including 10 pts in phase Ib and 20 pts in phase II with a median age of 63.5 yrs (range 36-75) were enrolled across 4 US sites between June 2019 and July 2021. In phase Ib, one pt experienced DLT (grade 3 enterocolitis); RP2D was confirmed at dose level 0. All 30 pts were included in study reported outcomes with a median follow-up time of 10.7 mo. Median PFS was 4.2 mo (95% CI, 1.9-10.2) and failed to reject the null hypothesis. Median OS was 7.5 mo (95% CI, 5.8-21.4). The 75 th percentile estimates for PFS and OS are 10.2 mo (95% CI, 5.4-NE) and 21.4 mo (95% CI, 7.8-21.4). ORR estimates and toxicity data are pending and will be presented at the meeting. Conclusions: The observed median PFS is insufficient to reject the null hypothesis. The 75 th percentile estimates for PFS and OS are suggestive of prolonged benefit with chemoimmunotherapy in a small fraction of patients with BTC. Clinical trial information: NCT03785873.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 7010-7010
    Abstract: 7010 Background: Despite evidence that rising cancer care costs are contributing to “financial toxicity” in cancer pts, no studies, to our knowledge, have prospectively assessed the financial impact of cancer diagnosis (dx) using both self-reported and objective financial measures. S1417CD, led by the SWOG Cancer Research Network and conducted in the NCI Community Oncology Research Program (NCORP), was the first national prospective cohort study to evaluate time-to-first evidence of major financial hardship (MFH) in pts with newly diagnosed mCRC. We present results of the primary endpoint analysis. Methods: Pts age ≥ 18 within 120 days of mCRC dx receiving systemic treatment completed surveys every 3 months (mo) for 12 mo. MFH was defined as ≥ 1 occurrence of self-reported increase in debt, new loans, selling home, refinancing home, or ≥ 20% income decline during the 12 mo study period. Cumulative incidence (CI) of MFH was estimated to account for competing risk of death. Additional endpoints, not reported here, included quality of life, caregiver strain, and changes in credit status over 12 mo. Results: In total, 380 pts (median age 59.9) across 126 clinic sites were enrolled, with 377 eligible and evaluable for the primary endpoint (reached 12 mo assessment, death, or MFH endpoint); complete data were available for 92% of pts as of Jan 23, 2020. Most pts were white (78%), male (61%), and insured (98%), with annual income ≤ $50,000 (56%). Cumulative incidence of MFH at 12 mo was 71.5% (95% CI: 65.9%-76.3%), with 24.6%, 52.4%, and 61.8% at 3, 6, and 9 mo. The dominant components of MFH were new debt (12-mo CI, 56.7%) and 〉 20% decline in income (26.7%); 104 (41%) pts reported ≥ 2 elements of MFH. In a secondary analysis excluding new debt, 12 mo cumulative incidence of MFH was 42.9% (95% CI: 37.2%-48.5%), with 10.3%, 24.4%, and 31.9% at 3, 6, and 9 mo. Conclusions: In a national sample of mCRC pts on systemic tx, financial hardship, most commonly in the form of increased debt, accumulates progressively over time. Nearly 3 out of 4 pts experiencing MFH at 12 mo despite access to health insurance coverage. These findings underscore the need for clinic and policy solutions such as early financial navigation and elimination of cost sharing to protect pts from financial devastation as they continue with tx. Clinical trial information: NCI-2015-01885 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 4_suppl ( 2022-02-01), p. 517-517
    Abstract: 517 Background: Pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death, with a recurrence rate of 85% after curative surgery and a 5-year survival rate of 10%. Serum biomarkers like CA 19-9 lack sensitivity and specificity (10% of patients fail to produce CA 19-9), and are poor indicators of molecular residual disease (MRD). Circulating tumor DNA (ctDNA) detection allows for MRD identification months ahead of radiological findings, and may assess molecular response and patient outcomes. Methods: A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection and quantification of ctDNA in a prospective clinical cohort of patients. Serial time points were collected for unresectable, borderline resectable, and resectable subsets of patients to monitor ctDNA levels in response to treatment (see Table). Results: 93 patients were included, with a median age of 67.3 yrs and 45% female. 285 timepoints were analyzed for ctDNA presence, with each patient having between 1 and 7 timepoints (median 3 timepoints per patient). 46 patients had one or more samples positive for ctDNA, resulting in an anytime ctDNA positivity rate of 49.5%. Anytime positivity correlated with the stage of disease (p 〈 0.001). Within ctDNA-positive samples, observed levels were 0.04-1227 mean tumor molecules per mL of plasma (mean 35.1, median 1.02 MTM/mL). During the follow-up period (median 13.5 months, range 1-80 months), 36 patients had recurrence or disease progression events. Recurrence-free survival (RFS) strongly correlated with post-operative anytime ctDNA positivity: Hazards Ratio 8.0 (95% CI 3.4-18.7), p =1.6e-6. For 49 patients, CA 19-9 measurements were available. Elevated CA 19-9 was not correlated with RFS (p=0.35). Conclusions: Our study demonstrates the feasibility of tumor-informed ctDNA-based MRD testing in PDAC, in 93 patients of all stages. ctDNA positivity correlated with patient survival outcomes more strongly than CA19-9. Our data suggests patients can benefit from personalized and tumor-informed MRD testing.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 3_suppl ( 2024-01-20), p. 687-687
    Abstract: 687 Background: The NAPOLI 3 study (NCT04083235, N = 770) reported that NALIRIFOX improved overall survival (OS) vs Gem+NabP with manageable toxicity in 1L treatment of metastatic pancreatic adenocarcinoma. We explored changes in CA19-9 levels and their potential associations with efficacy as an important tumor marker in pancreatic adenocarcinoma. Methods: In NAPOLI 3, CA19-9 was evaluated at baseline and every 8 weeks until patients discontinued study treatment. The detection limit of CA19-9 was 8000 kU/L in this study. The Cox proportional hazards regression and logistic regression were employed to investigate the relationship between CA19-9 decrease and OS, progression-free survival (PFS), and overall response rate (ORR). Results: Patients with evaluable CA19-9 (levels = 〈 8000) at baseline and additional measurements at weeks 8 and 16 were included in the analysis (NALIRIFOX, n = 179; Gem+NabP, n = 194). The median baseline CA19-9 level was 378.0 and 409.7 kU/L for the NALIRIFOX and Gem+NabP arms, respectively. Overall, patients with (vs without) any CA 19-9 decrease by week 16 had a higher ORR (59.9% vs 35.2%; p = 0.002), a longer median PFS (9.2 vs 6.2 months; p 〈 0.001) and a longer median OS (14.2 vs 8.7 months; p = 0.005), respectively in a pooled analysis of the treatments. In the NALIRIFOX arm, patients with any CA19-9 decrease by week 16 had a higher confirmed ORR of 65.1% compared with those without at 42.4% ( p 〈 0.001), a median PFS of 9.5 vs 7.1 months ( p 〈 0.001) and a median OS of 15.4 versus 8.4 months ( p = 0.004), respectively. In the Gem+NabP arm, patients with CA19-9 decrease by week 16 had a higher ORR of 55.5% compared with those without at 23.8% ( p = 0.012), a median PFS of 7.6 versus 5.8 months ( p 〈 0.001) and a median OS of 13.7 versus 11.9 months ( p = 0.235), respectively. Conclusions: CA19-9 decrease by week 16 has the potential to be an early prognostic factor for OS, PFS and ORR. The results should be interpreted with caution as a considerable percentage of patients were excluded due to non-evaluable CA19-9 that exceeded the lab detection limit of 8000 kU/L. Clinical trial information: NCT04083235 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 42, No. 16_suppl ( 2024-06-01), p. TPS11587-TPS11587
    Abstract: TPS11587 Background: Advanced cancers driven by mutations at or downstream of receptor tyrosine kinases (RTKs), including KIT- and PDGFRA-mutant gastrointestinal stromal tumor (GIST), activate autophagy as an escape mechanism in response to RTK pathway inhibitors. ULK1/2 kinases are key regulators that initiate autophagy in response to stress, such as KIT/PDGFRA inhibition in KIT- and PDGFRA-mutant GIST. Therefore, ULK1/2 inhibition represents a potential targeted approach to selectively inhibit autophagy and is an attractive strategy for combination with RTK pathway inhibitors, including ripretinib. Ripretinib is a switch-control KIT/PDGFRA tyrosine kinase inhibitor approved as a ≥fourth-line therapy for advanced GIST. In the INTRIGUE trial, ripretinib demonstrated comparable efficacy and more favorable safety compared with sunitinib in second-line advanced GIST. DCC-3116 is an investigational, selective, potent, switch-control kinase inhibitor of ULK1/2 in development for combination with targeted therapies that activate autophagy, such as ripretinib. In a GIST xenograft model, animals treated with ripretinib demonstrated stable tumor burden while treatment with ripretinib + DCC-3116 resulted in complete regressions. Here, we describe the design of a phase 1/2, multicenter, open-label study evaluating the safety, recommended phase 2 dose (RP2D), and preliminary efficacy of DCC-3116 in combination with ripretinib in advanced GIST (NCT05957367). Methods: This phase 1/2 study includes safety/dose-finding (part 1) and expansion (part 2). In part 1, patients (pts) ≥18 years must have pathologically confirmed GIST with a KIT or PDGFRA mutation and disease progression on or intolerance to ≥1 systemic regimen. Escalating doses of DCC-3116 will be assessed with ripretinib 150 mg once daily. Part 1 will use safety, pharmacokinetics, pharmacodynamics, preliminary efficacy, and a Bayesian optimal interval design to identify the RP2D for part 2 and the maximum tolerated dose. In part 2, second-line pts with confirmed GIST with a KIT exon 11 mutation and disease progression on or intolerance to first-line imatinib will be enrolled. Part 2 will use a two-stage design with non-binding futility and efficacy analyses after stage 1 to explore efficacy of the combination dose selected in part 1. Exclusion criteria for both parts include use of other anticancer treatments, such as ripretinib, and any investigational therapies within 14 days, use of moderate or strong inhibitors or inducers of cytochrome P450 3A4 or P-glycoprotein, symptomatic central nervous system metastases or leptomeningeal disease, and active infections. Primary objectives in part 1 are to identify adverse events and the RP2D. The primary objective of part 2 is to determine the objective response rate per modified Response Evaluation Criteria in Solid Tumors version 1.1. The study is currently enrolling. Clinical trial information: NCT05957367 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2024
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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