- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, emilumenib succinate (DS-1594) / Daiichi Sankyo
Trial completion date, Trial primary completion date, Combination therapy: DS-1594b With or Without Azacitidine, Venetoclax, or Mini-HCVD for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia (clinicaltrials.gov) - Mar 16, 2023
P1/2, N=20, Active, not recruiting,
The in vitro studies showed that the leucovorin was the most active inhibitor of the S1-glycoprotein/NRP-1 complex formation, with an IC value of 185.95 Trial completion date: Nov 2022 --> Nov 2024 | Trial primary completion date: Nov 2022 --> Nov 2024
- |||||||||| Teysuno (gimeracil/oteracil/tegafur) / Nordic Group, Otsuka, Tomudex (raltitrexed) / Pfizer, AstraZeneca, Elunate (fruquintinib) / Takeda
Clinical, Journal, Metastases: Using a combination of fruquintinib, raltitrexed, and S-1 as a third-line treatment for metastatic colorectal cancer with co-existence of Hodgkin lymphoma: a case report. (Pubmed Central) - Mar 15, 2023
Fruquintinib, regorafenib, trifluridine/tipiracil (TAS-102), panitumumab and cetuximab combined with single-agent chemotherapy regimens are currently recommended as third-line therapies for patients exhibiting disease progression...The mFOLFOX6 regimen was administered...Liver metastases (intestinal-type adenocarcinoma) were detected in November 2018, and second-line therapy with the FOLFIRI regimen was initiated in January 2019...Third-line therapy with fruquintinib, raltitrexed, and S-1 achieved a PR that permitted surgical resection and enabled a relatively long progression-free survival. The findings suggest that the three agents regimen might be clinically effective as late-line therapy for mCRC.
- |||||||||| 5-fluorouracil / Generic mfg.
Journal: Tailored chemotherapy for colorectal cancer peritoneal metastases based on a drug-screening platform in patient-derived organoids: a case report. (Pubmed Central) - Mar 15, 2023
The patient was treated with systemic chemotherapy (FOLFOXIRI plus Bevacizumab) and was subjected to mitomycin-based PIPAC...Our results suggest that the peritoneal implant shows chemoresistance to oxaliplatin, while it might still be sensitive to irinotecan and 5-FU, which supports a potential benefit of these two drugs in the local and/or systemic treatment of our patient. This study shows the strength of the utility of the establishment of organoids for drug response assays and thus, for the personalized treatment of colorectal carcinomatosis patients.
- |||||||||| 5-fluorouracil / Generic mfg.
The effects of cytotoxic chemotherapy on colorectal cancer immunogenicity (Section 24; Poster Board #15) - Mar 14, 2023 - Abstract #AACR2023AACR_8501;
CSC expression (CD44, CD133, CD117, and EpCAM) was found to be enriched under therapeutic challenge with gem and nab-pac containing chemotherapy. Chemotherapy agents included the commonly used cytotoxic drugs 5-fluorouracil (5FU), oxaliplatin, SN38 (the active metabolite of irinotecan), cisplatin, and temozolomide, used as single drugs or combinations, in a pulsatile schedule using weekly
- |||||||||| 5-fluorouracil / Generic mfg.
A novel second-generation nano-fluoropyrimidine to treat metastatic colorectal cancer and overcome 5-fluorouracil resistance (Section 17; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_8330;
While using 5-FU-based regimens such as FOLFOX and FOLFIRI in combination with biologics confer a survival benefit, their ineffectiveness at promoting long-term survival in a substantial fraction of mCRC patients and associated toxicities limits their use...Our findings suggest the significance of elevated TS in CRC metastatic progression and 5-FU resistance and demonstrate that CF10 may be effective at inhibiting CRC metastatic progression. CF10 may be a successful candidate for early-phase clinical trials to treat mCRC.
- |||||||||| IGM-8444 / IGM Biosciences
Characterization of the synergistic tumor cytotoxicity of agonistic DR5 IgM antibody IGM-8444 with chemotherapeutic agents (Section 15; Poster Board #3) - Mar 14, 2023 - Abstract #AACR2023AACR_8281;
P1a/1b
In summary, IGM-8444 shows in vitro cytotoxicity and in vivo PD and anti-tumor efficacy responses in preclinical models, with enhanced activity in combination with several classes of chemotherapies reported to upregulate DR5 expression. IGM-8444 combination with FOLFIRI standard of care is currently under evaluation in a Phase 1 study in patients with metastatic colorectal cancer (NCT04553692).
- |||||||||| Avastin (bevacizumab) / Roche
Cell-free DNA fragmentation profiling for monitoring therapeutic response in metastatic colorectal cancer (Valencia D - Convention Center) - Mar 14, 2023 - Abstract #AACR2023AACR_7863;
P3
Changes in DELFI-TF scores during first-line FOLFOX/FOLFIRI and bevacizumab therapy were assessed to predict disease response... DELFI-TF demonstrates the ability to use cfDNA fragmentomes to estimate cfDNA tumor burden with a performance comparable to standard approaches for treatment response monitoring and clinical outcome prediction.
- |||||||||| Saltikva (attenuated Salmonella typhimurium expressing IL-2) / MD Biosciences, Salspera
Addition of Salmonella-IL2 to FOLFIRINOX for metastatic stage 4 pancreatic cancer nearly doubles median survival (Chapin Theater - Convention Center) - Mar 14, 2023 - Abstract #AACR2023AACR_7817;
Addition of Salmonella-IL2 to FOLFIRINOX for stage 4 metastatic pancreatic cancer results in the near doubling of median survival when compared to historical and site-specific controls receiving FOLFIRNOX only. These findings strongly indicate that a larger pivotal phase 3 multicenter trial is warranted.
- |||||||||| Potentiating immunogenicity of PD1 blockage with metronomic Oral CAPOX for local and liver metastasized colorectal cancer (Section 21; Poster Board #25) - Mar 14, 2023 - Abstract #AACR2023AACR_7431;
And after the advent of capecitabine, an oral prodrug of 5-FU, both FOLFOX and CAPOX remain the first-line treatment for local and advanced CRC...Because Oral CAPOX therapy converts macrophage more immunogenic, Oral CAPOX therapy could reverse immunosuppressive tumor microenvironment of liver metastasized colorectal cancer. Oral CAPOX and anti-PD1 combination is treated liver metastasized CRC model and showed standing out antitumor efficacy, and T cell activation.
- |||||||||| 5-fluorouracil / Generic mfg., oxaliplatin / Generic mfg., irinotecan / Generic mfg.
Targeting MEK activity in pancreatic tumors resistant to the combination of 5FU, irinotecan, and oxaliplatin promotes response to immunotherapy (Section 34; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_6727;
FOLFIRINOX, a chemotherapy regimen consisting of 5FU, Leucovorin, Irinotecan, and Oxaliplatin, has been a first-line standard of care for patients with pancreatic adenocarcinoma (PDAC) for the last decade...Importantly, Trametinib sensitizes FIO-resistant tumors to anti-PD-1 therapy, with the combination treatment significantly enhancing the cytolytic activity of the infiltrating CD8+ T cells and increasing tumor cell death. Taken together, our findings identify enhanced MEK/ERK signaling as a therapeutic target in FOLFIRINOX-resistant PDAC tumors, and suggest evaluating the combination of Trametinib and anti-PD-1 therapy in patients who progress on FOLFIRINOX.
- |||||||||| 5-fluorouracil / Generic mfg., oxaliplatin / Generic mfg., leucovorin calcium / Generic mfg.
Tumor evolution and immune microenvironment dynamics define response to neoadjuvant treatment of esophageal adenocarcinoma (Section 44; Poster Board #18) - Mar 14, 2023 - Abstract #AACR2023AACR_5984;
This study identifies profound transcriptional changes during treatment with limited evidence that clonal replacement is the cause, suggesting phenotypic plasticity as a mechanism for therapy resistance. The presence of immune escape, a less activated T-cell phenotype and a lack of clonal T-cell expansions in patients with poor clinical treatment response has high pharmacological relevance and could be exploited via combined immune-chemotherapy treatments.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Opdivo (nivolumab) / Ono Pharma, BMS
The Efficacy of Immune Checkpoint Inhibitors in Advanced Biliary Tract Cancer with KRAS Mutation (Section 39; Poster Board #16) - Mar 14, 2023 - Abstract #AACR2023AACR_5958;
All patients received gemcitabine plus cisplatin as the frontline therapy, and 53.2% had fluoropyrimidine plus oxaliplatin (FOLFOX) before ICIs...In subgroup analysis, patients with both KRAS mutation and PD-L1 positivity had longer PFS as compared to patients with KRAS mutation and PD-L1 negativity (6.5 vs 2.6 months, p=0.047). This finding was not shown in patients with a wild type of KRAS.ConclusionThis analysis showed that PD-L1 expression might be a novel biomarker for ICIs in BTC patients with KRAS mutation but not the wild type of KRAS.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., irinotecan / Generic mfg.
IL-1 blockade prevents cardiac toxicity and improves immunotherapy efficacy (Section 40; Poster Board #2) - Mar 14, 2023 - Abstract #AACR2023AACR_5855;
In addition, we found that IL-1? blockers, which are already used in the clinic for cardiology indications, both reduce adverse events and simultaneously enhance the antitumor effects triggered by immunotherapy.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
Treatment of gastric cancer cells with tumor treating fields (TTFields) and concomitant FOLFOX (Section 15; Poster Board #26) - Mar 14, 2023 - Abstract #AACR2023AACR_4970;
TTFields show potential as an effective gastric cancer treatment, with a mechanism of action involving an anti-mitotic effect and DNA damage repair impairment. TTFields may be applied to enhance the efficacy of gastric cancer standard-of-care.
- |||||||||| 5-fluorouracil / Generic mfg.
Changes in HER3 expression associated with chemotherapy for pancreatic cancer (Section 44; Poster Board #15) - Mar 14, 2023 - Abstract #AACR2023AACR_4730;
HER3 expression with 3+/2+ is observed in 63% of pancreatic cancer patients, and HER3-expressing pancreatic cancer is of great interest as a therapeutic target. HER3 expression status may change before and after cytotoxic combination therapy in some cases of pancreatic cancer.
- |||||||||| Clinical impact of FGFR inhibitors on FGFR2 positive pancreatic cancer (Section 44; Poster Board #5) - Mar 14, 2023 - Abstract #AACR2023AACR_4720;
Patient 2 harbored an FGFR2-INA fusion with 12 months of stable disease to pazopanib after experiencing progression from chemotherapy... This retrospective analysis provides clinical evidence that there is a subpopulation of KRAS wild-type FGFR2 fusion positive pancreatic patients who can have beneficial and lasting responses to FGFR inhibitors further suggesting a need to investigate and expand the availability of FGFR inhibitors to more cancer types.
- |||||||||| 5-fluorouracil / Generic mfg.
Classical chemotherapy modulates cytokine secretion in the MSS CRC immune microenvironment and enhances T cell killing (Section 40; Poster Board #7) - Mar 14, 2023 - Abstract #AACR2023AACR_4665;
Most patients receive chemotherapies 5-FU and folinic acid combined with oxaliplatin, irinotecan, or both...5-FU + folinic acid + oxaliplatin -/+ pembrolizumab enhances TALL-104-mediated killing of SW480 and HT29 cells...Chemotherapy pre-treatment may enhance TALL-104 cell infiltration in MSI tumors. Future directions include evaluation of concurrent vs. sequential chemotherapy + immunotherapy regimens using murine models of MSS colorectal cancer and isolation of circulating tumor cells from patients before and after chemotherapy treatment to measure effects on cytokine secretion and immune cell killing.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., irinotecan / Generic mfg.
Novel expression biomarkers via prediction of response to FOLFIRINOX (FFX) treatment for PDAC (Section 9; Poster Board #9) - Mar 14, 2023 - Abstract #AACR2023AACR_4152;
All genes in the final model were among the top-7 most frequently selected genes across folds (selected between 23 and 48 times out of the 100 folds). hENT1, a previous biomarker of GA effectiveness, also shows separation of the survival curves on this data set, but less so than several of the identified genes.While additional biological validation and additional computational variations of the study design are required to confirm the genes and predictor, this analysis resulted in a robust candidate set of 5 genes from a large PDAC, FFX-treated cohort that individually are statistically significantly associated with response, and that together are more predictive of response to FFX in this data than all-gene models.
- |||||||||| MAPK and NF-kappaB signaling converge on the epigenome to transcriptionally activate genes involved in pancreatic cancer metastasis (Section 12; Poster Board #8) - Mar 14, 2023 - Abstract #AACR2023AACR_4112;
Current treatment methods (gemcitabine and nab-paclitaxel, FOLFIRINOX) are not sufficient for patients with late-stage disease and only modestly improve survival...Based on these observations, we aim to delineate the molecular mechanism involved in the synergism, investigate the role of the TME, and decipher the signaling interactions between PDAC tumor cells and cells of the TME. This study is the first comprehensive analysis of the synergism between MAPK and NF-?B signaling and will provide novel insights into the development of mechanism-based therapeutic approaches.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
Discovery of a novel PP2A activator as a potential therapeutic for FOLFOX resistant colon cancer (Section 18; Poster Board #12) - Mar 14, 2023 - Abstract #AACR2023AACR_3898;
And PP2A, being known as a regulator for many cellular processes, can be activated to assist in the degradation and inactivation of many signaling proteins such as c-myc, GSK3?, and ERK, which was observed in CRC cells treated with PPA24. Together, these results signify the potential of PPA24 to act as a novel PP2A activator in the treatment of CRC and FOLFOX-resistant CRC.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg., irinotecan / Generic mfg.
Development of a methylation-based classifier to identify pancreatic adenocarcinoma subtype (Section 39; Poster Board #30) - Mar 14, 2023 - Abstract #AACR2023AACR_2201;
We continue to develop a qPCR assay for PDAC subtype that so far has 80% accuracy using 14/20 probes. We are completing validation of the remaining 6 primers and correlating methylation levels at each site with those obtained from EPIC array methylation analysis.
- |||||||||| 5-fluorouracil / Generic mfg., leucovorin calcium / Generic mfg.
Trial completion date, Trial primary completion date, Metastases: Neoadjuvant FOLFOX Chemotherapy for Patients With Locally Advanced Colon Cancer (clinicaltrials.gov) - Mar 14, 2023
P3, N=560, Recruiting,
We are completing validation of the remaining 6 primers and correlating methylation levels at each site with those obtained from EPIC array methylation analysis. Trial completion date: Feb 2026 --> Dec 2029 | Trial primary completion date: Feb 2023 --> Dec 2026
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