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PROVIDER: PRJNA1283527 | ENA |
REPOSITORIES: ENA
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Project description:Newly-diagnosed IDHwt MGMT unmethylated glioblastoma patients treated with standard radiation, nivolumab, and BMS-986205 [scRNA-seq]
| PRJNA1212512 | ENA
Project description:Newly-diagnosed IDHwt MGMT unmethylated glioblastoma patients treated with standard radiation, nivolumab, and BMS-986205 [bulk RNA-seq]
| PRJNA1212513 | ENA
Project description:Improving immunotherapeutic efficacy for patients with glioblastoma (GBM) has been suggested to be limited by a number of factors including indoleamine 2,3 dioxygenease 1 (IDO; IDO1); an enzyme that converts L-tryptophan (Trp) into L-kynurenine (Kyn). Here, we report the results of a first-in-human phase 1 trial for 12 patients with newly-diagnosed IDHwt MGMT unmethylated GBM treated with standard radiation, nivolumab, and BMS-986205 – the latter being a potent IDO1 enzyme inhibitor. The treatment regimen was found to be safe and tolerable when administered at 50mg. Treated patients experienced decreased L-kynurenine levels without changes in L-tryptophan. No other kynurenine-pathway metabolites were altered while on treatment. The median overall survival (OS) was 11.5 months for all patients, with 4 individuals alive at ≥28 months, and 2 patients alive at 5 years post-diagnosis. Analysis of resected tumor at the time of first recurrence revealed intratumoral IDO1 expression to be primarily enriched in myeloid lineage cells. Higher systemic levels of naïve and early effector CD8+ T cells, higher systemic levels of microbial-derived aryl-lactates, lower systemic levels of microbial-derived aryl acetates, higher levels of fecal-derived Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, Phocaeicola plebeius, an age of <65 years old, and patients who underwent subtotal but not gross total tumor resection, were significantly more likely to live past 28 months while on treatment. This study provides a biological rationale for use of RT, PD-1 mAb, and IDO1 enzyme inhibitor treatment in temodar naïve GBM patients who survive well after 2 years while on treatment (ClinicalTrials.gov: NCT04047706).
2025-06-02 | GSE287371 | GEO
Project description:Improving immunotherapeutic efficacy for patients with glioblastoma (GBM) has been suggested to be limited by a number of factors including indoleamine 2,3 dioxygenease 1 (IDO; IDO1); an enzyme that converts L-tryptophan (Trp) into L-kynurenine (Kyn). Here, we report the results of a first-in-human phase 1 trial for 12 patients with newly-diagnosed IDHwt MGMT unmethylated GBM treated with standard radiation, nivolumab, and BMS-986205 – the latter being a potent IDO1 enzyme inhibitor. The treatment regimen was found to be safe and tolerable when administered at 50mg. Treated patients experienced decreased L-kynurenine levels without changes in L-tryptophan. No other kynurenine-pathway metabolites were altered while on treatment. The median overall survival (OS) was 11.5 months for all patients, with 4 individuals alive at ≥28 months, and 2 patients alive at 5 years post-diagnosis. Analysis of resected tumor at the time of first recurrence revealed intratumoral IDO1 expression to be primarily enriched in myeloid lineage cells. Higher systemic levels of naïve and early effector CD8+ T cells, higher systemic levels of microbial-derived aryl-lactates, lower systemic levels of microbial-derived aryl acetates, higher levels of fecal-derived Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, Phocaeicola plebeius, an age of <65 years old, and patients who underwent subtotal but not gross total tumor resection, were significantly more likely to live past 28 months while on treatment. This study provides a biological rationale for use of RT, PD-1 mAb, and IDO1 enzyme inhibitor treatment in temodar naïve GBM patients who survive well after 2 years while on treatment (ClinicalTrials.gov: NCT04047706).
2025-06-02 | GSE287372 | GEO
Project description:Improving immunotherapeutic efficacy for patients with glioblastoma (GBM) has been suggested to be limited by a number of factors including indoleamine 2,3 dioxygenease 1 (IDO; IDO1); an enzyme that converts L-tryptophan (Trp) into L-kynurenine (Kyn). Here, we report the results of a first-in-human phase 1 trial for 12 patients with newly-diagnosed IDHwt MGMT unmethylated GBM treated with standard radiation, nivolumab, and BMS-986205 – the latter being a potent IDO1 enzyme inhibitor. The treatment regimen was found to be safe and tolerable when administered at 50mg. Treated patients experienced decreased L-kynurenine levels without changes in L-tryptophan. No other kynurenine-pathway metabolites were altered while on treatment. The median overall survival (OS) was 11.5 months for all patients, with 4 individuals alive at ≥28 months, and 2 patients alive at 5 years post-diagnosis. Analysis of resected tumor at the time of first recurrence revealed intratumoral IDO1 expression to be primarily enriched in myeloid lineage cells. Higher systemic levels of naïve and early effector CD8+ T cells, higher systemic levels of microbial-derived aryl-lactates, lower systemic levels of microbial-derived aryl acetates, higher levels of fecal-derived Massilioclostridium coli, GGB3819-SGB5184, Dysosmobacter welbionis, Phocaeicola plebeius, an age of <65 years old, and patients who underwent subtotal but not gross total tumor resection, were significantly more likely to live past 28 months while on treatment. This study provides a biological rationale for use of RT, PD-1 mAb, and IDO1 enzyme inhibitor treatment in temodar naïve GBM patients who survive well after 2 years while on treatment (ClinicalTrials.gov: NCT04047706).
2026-05-06 | GSE300413 | GEO
Project description:Tumor core needle biopsies from kidney or metastatic sites obtained at trial enrollment i.e. Screen and/or at Cycle 2 Day 8 (i.e.Week 4) from metastatic clear cell RCC patients treated with 0.2mpk, 3mpk or 10mpk (as 2nd or further line of therapy; Arms A,B,C) or 10mpk (as first line therapy; Arm D) of nivolumab (BMS-936558,MDX-1106) on Bristol-Myers Squibb clinical trial protocol CA209-009.
2016-05-15 | E-MTAB-3218 | biostudies-arrayexpress
Project description:Blood samples obtained at Cycle 1 Day 1, Cycle 1 Day 2 or at Cycle 2 Day 8 (i.e. before treatment, 24 hours after treatment or Week 4) from metastatic clear cell RCC patients treated with 0.2mpk, 3mpk or 10mpk (as 2nd or further line of therapy; Arms A,B,C) or 10mpk (as first line therapy; Arm D) of nivolumab (BMS-936558,MDX-1106) on Bristol-Myers Squibb clinical trial protocol CA209-009.
2016-05-15 | E-MTAB-3219 | biostudies-arrayexpress
Project description:Glioblastoma multiforme (GBM), a WHO grade IV glioma is the most common and malignant primary cancer of the central nervous system with a grim median survival of 16 to 17 months upon diagnosis. Radiotherapy is the standard first line treatment for newly diagnosed patients with gliomas, but its effectiveness is limited given their intrinsic resistance and propensity for recurrence. Although possible mechanisms have been attributed to GBM resistance to radiation treatments, the molecular mechanisms regulating radiation resistance of GBM are still unclear.
2019-07-23 | GSE86213 | GEO
Project description:Background: Targeting tumor-associated macrophages through C-C chemokine receptor type 2 (CCRs) in pancreatic ductal adenocarcinoma (PDAC) improves the efficacy of chemotherapy and restores T cell immunity. Methods: We conducted a phase I/II single institution study (NCT03496662) combining chemotherapy gemcitabine and nab-paclitaxel (GnP), an oral CCR2/5 inhibitor BMS-813160 and nivolumab for four 28-day cycles as a neoadjuvant therapy for patients with borderline resectable (BR) or locally advanced (LA) PDAC. The recommended phase 2 dose (RP2D) of BMS-813160 was established in the standard 3+3 design. Primary end points were safety and objective response rate (ORR). Secondary end points included resection rate, progression-free survival (PFS) and overall survival (OS). Results: 8 patients were treated with GnP alone (control arm) and 31 patients (29 response evaluable) were treated at RP2D. No grade 3 or 4 toxicities attributed to nivolumab or BMS-813160 were identified. After all 4 cycles of study treatment (N=26), ORR was 35.7%, 16.7% among BR- and LA-PDAC patients, compared to 0% of control arm patients. 78.6% BR- and 16.7% of LA-PDAC patients who completed study treatment underwent surgical resection. For intent-to-treat analyses, BR-PDAC patients had a mPFS and mOS of 14.6 and 20.4 months respectively; and LA-PDAC patients had a mPFS and mOS of 14.7 and 17 months respectively. Single cell RNAseq analysis showed enhanced proliferating CD4 and CD8 T cells and gene signatures indicative of effector function. Conclusions: Neoadjuvant BMS-813160/nivolumab/GnP was well tolerated and appears to achieve higher ORR and resectability than historical data, warranting a larger randomized phase II study.
2025-03-11 | GSE288533 | GEO
Project description:Total RNA microarray data from Fresh-Frozen Glioblastoma tumor samples. Untreated, newly diagnosed patients.
2014-08-08 | E-GEOD-60184 | biostudies-arrayexpress