Publications by authors named "Andrew Coveler"
Article Synopsis
- Denileukin diftitox (ONTAK) is a fusion protein that can deplete regulatory T cells, which are linked to poor outcomes in ovarian cancer, and this study aimed to assess its safety and effects when given directly into the abdomen of patients with advanced ovarian cancer.
- A phase I trial included 10 patients who received ONTAK at escalating doses, revealing a maximum tolerated dose of 15 μg/kg with mostly mild side effects, though one patient experienced a severe reaction at the highest dose.
- While some patients showed a decrease in CA-125 levels (a marker for ovarian cancer), there were no significant changes in the overall cancer response, although ONTAK successfully reduced regulatory T cells in both blood and
Article Synopsis
- The study explores the use of a CD73 inhibitor (oleclumab) combined with durvalumab and chemotherapy in treating pancreatic ductal adenocarcinoma (PDAC), targeting immune surveillance evasion.
- Conducted across multiple centers, the trial included patients with metastatic PDAC in two cohorts, assessing safety and response rates with various treatment combinations for the chemotherapy regimens.
- While safety results were acceptable, the trial did not achieve its main goal of demonstrating significant treatment efficacy, although some patients with high CD73 levels showed improved outcomes.
Article Synopsis
- AbGn-107 is an antibody-drug conjugate targeting the AG-7 antigen, found in various gastrointestinal cancers, which showed promising results in preclinical studies and led to a Phase I trial for GI cancers.
- The trial used a 3+3 dose escalation design, enrolling 39 patients with advanced, recurrent GI cancers, focusing on safety, maximum tolerated dose, and efficacy with doses ranging from 0.1 to 1.0 mg/kg.
- Findings indicated that AbGn-107 was generally well-tolerated with some serious side effects; one patient showed a partial response, and nearly half had stable disease, suggesting modest clinical activity and the need for further research on AG-7 as a therapeutic target.
Article Synopsis
- - Recent trials indicate that PD-1-directed immunotherapy, specifically pembrolizumab, may help some patients with anal squamous cell carcinoma, but there is a need for reliable biomarkers to predict who will respond to the treatment.
- - In a phase II clinical trial involving 32 patients, the objective response rate (ORR) to pembrolizumab was low at 9.4%, with a median progression-free survival of only 2.2 months, and most patients showed low levels of beneficial immune cells.
- - Some patients had long-term responses to pembrolizumab, with one patient lasting over 5 years, particularly those with HPV-positive tumors and no liver metastases, but challenges remain due to ongoing HPV infection
Article Synopsis
- Assessing clinical tumor response after total neoadjuvant therapy (TNT) is crucial for determining if patients with advanced rectal cancer can undergo watch-and-wait treatment instead of surgery.
- The study analyzed outcomes related to organ preservation and survival rates based on a new three-tier grading system for tumor response (complete, near-complete, and incomplete) in a diverse group of patients.
- Results included data from 304 patients, showing that age and sex were consistent across response grades, helping inform eligibility for organ preservation strategies based on clinical outcomes.
Phase I Study of Elraglusib (9-ING-41), a Glycogen Synthase Kinase-3β Inhibitor, as Monotherapy or Combined with Chemotherapy in Patients with Advanced Malignancies.
Benedito A Carneiro Ludimila Cavalcante Devalingam Mahalingam Anwaar Saeed Howard Safran Andrew L Coveler
Clin Cancer Res
February 2024
Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied.
Patients And Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy.
Results: Patients received monotherapy (n = 67) or combination therapy (n = 171) elraglusib doses 1 to 15 mg/kg twice weekly.
Article Synopsis
- - The OPRA trial studied the long-term outcomes of different treatment sequences for stage II/III rectal cancer, comparing induction chemotherapy followed by chemoradiation (INCT-CRT) with chemoradiation followed by consolidation chemotherapy (CRT-CNCT) to evaluate organ preservation and oncologic results.
- - After a median follow-up of 5.1 years with 324 patients, the 5-year disease-free survival (DFS) rates were similar for both treatment groups, while TME-free survival was significantly higher in the CRT-CNCT group (54% vs. 39%).
- - The study found that most tumor regrowth occurred within the first 2 years for patients who opted for the watch-and-w
Article Synopsis
- Pancreatic ductal adenocarcinoma (PDA) is a highly deadly cancer, with standard treatment leading to a median survival of only 24 months; this study aimed to explore a multiagent perioperative therapy to enhance survival rates.
- In a phase 2 trial, patients received a combination of chemotherapy and radiation before and after surgery; results showed a median overall survival of 31.6 months, increasing to 58.1 months for those who completed the surgery.
- The study suggests that the examined perioperative therapy could offer a promising new treatment strategy for patients with potentially resectable PDA, potentially improving outcomes significantly.
Background: SEA-CD40 is an investigational, non-fucosylated, humanized monoclonal IgG antibody that activates CD40, an immune-activating tumor necrosis factor receptor superfamily member. SEA-CD40 exhibits enhanced binding to activating FcγRIIIa, possibly enabling greater immune stimulation than other CD40 agonists. A first-in-human phase 1 trial was conducted to examine safety, pharmacokinetics, and pharmacodynamics of SEA-CD40 monotherapy in patients with advanced solid tumors and lymphoma.
View Article and Find Full Text PDFUse of acupuncture with acupressure in addition to standard-of-care cryotherapy to decrease chemotherapy-associated neuropathy in patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy: Study protocol for a randomized, controlled pilot and feasibility study.
Contemp Clin Trials
August 2023
Article Synopsis
- - Oxaliplatin is a chemotherapy drug used to treat gastrointestinal cancers, but it can cause chemotherapy-induced peripheral neuropathy (CIPN), limiting treatment effectiveness.
- - A pilot study is being conducted with 56 patients to investigate if acupuncture and acupressure can reduce CIPN and other chemotherapy-related side effects during treatment with 5-fluorouracil (5-FU) and oxaliplatin.
- - Participants are randomly assigned to receive either acupuncture with self-acupressure or standard treatment, and various symptoms and side effects will be assessed over three months to evaluate the effectiveness and feasibility of this approach.
Article Synopsis
- HER2 is a critical target for treatment in metastatic colorectal cancer, leading to a study evaluating the combined effects of tucatinib and trastuzumab on patients who have not responded to chemotherapy.
- The MOUNTAINEER study analyzed patients aged 18 and older with HER2-positive, RAS wild-type colorectal cancer across various sites in five countries, first as a single-cohort and later expanding participation based on interim results.
- A total of 117 patients were enrolled, with most receiving treatment in different cohorts to assess the drug's effectiveness and safety, highlighting the ongoing nature of the research and its registration on ClinicalTrials.gov.
Article Synopsis
- High levels of type I T cells are essential for effectively targeting tumors, and this study explored the expansion of HER2-specific T cells from vaccinated patients for potential therapeutic use.
- In a Phase I/II trial, 19 patients received ex vivo-expanded HER2-specific T cells after being primed with a peptide-based vaccine, with results indicating good tolerability and significant boosts in targeted T cell levels.
- While there were no complete responses, some patients experienced disease stabilization and improved overall survival, highlighting the approach's feasibility and low toxicity.
Article Synopsis
- - The study investigated the effects of sotorasib, a KRAS G12C inhibitor, on patients with p.G12C-mutated pancreatic cancer who had previously undergone treatment, focusing on safety and efficacy.
- - A total of 38 patients participated, with 21% experiencing a confirmed objective response to the treatment, while median progression-free survival and overall survival were recorded at 4.0 months and 6.9 months, respectively.
- - The treatment was generally well-tolerated, with 42% of patients reporting adverse events; however, none were fatal or led to stopping the treatment.
Article Synopsis
- A study investigated a plasmid-based vaccine targeting the ERBB2 protein in patients with advanced-stage ERBB2-positive breast cancer to enhance immune response post-trastuzumab therapy.
- The trial included 66 participants and assessed safety and immune response to three different doses (10, 100, and 500 μg) of the vaccine, with most side effects being mild.
- Results showed that the 100 μg and 500 μg doses seemed to generate stronger immune responses, while DNA persistence at the injection site was also monitored over time.
Article Synopsis
- KRAS variant alleles can influence the biological behavior of pancreatic ductal adenocarcinomas (PDA), affecting patient prognosis and treatment options.
- A study at the University of Washington analyzed advanced PDA patients, revealing that specific KRAS mutations, particularly G12R, were linked to better overall and progression-free survival compared to other variants.
- However, having PI3K pathway mutations alongside KRAS G12R diminished this survival advantage, suggesting that the KRAS/PI3K genomic profile can help predict treatment responses in PDA patients.
Purpose: To evaluate the significance of CT perfusion parameters predicting response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC).
Materials And Methods: Seventy patients with PDAC prospectively had CT perfusion acquisition incorporated into baseline multiphase staging CT. Twenty-eight who were naïve to therapy were retained for further investigation.
Article Synopsis
- A clinical trial was conducted to evaluate the effectiveness of a watch-and-wait strategy in preserving organs for patients with locally advanced rectal cancer after total neoadjuvant therapy, involving 324 patients.
- Both groups receiving different treatment sequences (induction chemotherapy followed by chemoradiotherapy vs. chemoradiotherapy followed by consolidation chemotherapy) showed a similar 3-year disease-free survival (DFS) rate of about 76%.
- Results indicated that approximately half of the patients could avoid total mesorectal excision (TME) while maintaining survival rates comparable to historical data, suggesting organ preservation is a viable option.
Article Synopsis
- The study evaluated the combination of pembrolizumab (an immune checkpoint inhibitor) and carboplatin (a chemotherapy) in patients with recurrent platinum-resistant ovarian cancer, showing generally low response rates but some signs of stability in disease.
- Among 29 treated patients, only 10.3% achieved a partial response, but 51.7% had stable disease, indicating that while the treatment had limited effectiveness, some patients experienced no further progression.
- The treatment was relatively well tolerated, with common side effects being mild lymphopenia and anemia, and notable immune responses were observed, particularly in PD-L1-positive patients who fared better overall.
Article Synopsis
- Researchers investigated if overexpressed proteins linked to colorectal cancer could be used as effective vaccine targets to prevent tumor development in certain mouse models.
- They identified several antigens (CDC25B, COX2, RCAS1, FASCIN1) that showed higher immune responses in colorectal cancer patients, indicating their potential as vaccine candidates.
- Experiments showed that vaccination with CDC25B or COX2 peptides significantly reduced tumor growth in mice, while RCAS1 did not demonstrate any anti-tumor effect, highlighting the potential of these antigens in cancer immunotherapy.
Article Synopsis
- The study investigated a T-helper 1 selective vaccine targeting IGFBP-2 in advanced ovarian cancer patients to elicit strong immune responses and minimize regulatory T cell activity.
- In a phase I trial involving 25 patients, the vaccine was well tolerated and yielded high levels of IFNγ secreting T cells in 50% of participants, with significant increases in certain T cell subsets.
- The findings suggest that the IGFBP-2 vaccine effectively promotes desired type I T cell responses while avoiding regulatory T cell generation, indicating its potential for cancer immunotherapy.
Background: The Pancreatic Cancer Action Network (PanCAN) Patient Registry is an online, pancreatic cancer-specific, global registry enabling patients to self-report sociodemographics, disease/management characteristics, and patient-reported outcomes (PROs). We sought to describe the creation, user experience, and research potential of the PanCAN Registry.
Methods: We obtained data to describe (1) the creation of the Registry (questionnaire development, marketing efforts, and regulatory considerations); (2) the user experience (user characteristics and interactions with the registry following inception); and (3) the research potential of the registry (comparing PROs and treatment patterns by age [±65 years] and treatment site [community or academic] for users with de novo metastatic disease).
Article Synopsis
- Glycogen synthase kinase-3 beta (GSK-3β) plays an important role as a protooncogene in solid tumors, particularly pancreatic cancer, influencing processes like cell proliferation, survival, invasion, and metastasis.
- Its abnormal expression levels in the nucleus are linked to poorer tumor differentiation and survival outcomes in pancreatic cancer models.
- Promising results from small molecule inhibitors of GSK-3β in pre-clinical trials are leading to early clinical evaluations, with potential for combining these inhibitors with chemotherapy and immunotherapy in future treatments.
Article Synopsis
- - Pain is a common issue for patients with pancreatic cancer, stemming from factors like enzyme insufficiency, nerve obstruction, and tumor pressure, ultimately impacting their overall health.
- - Effective pain management is crucial for enhancing both the quality and length of life for these patients, although there's a lack of specific data addressing their unique pain management needs.
- - A comprehensive review of available treatment options suggests that implementing best practices for supportive care can significantly help in managing pain and improving patients' life experiences.
Article Synopsis
- The study aimed to compare the effectiveness and safety of algenpantucel-L immunotherapy combined with standard chemotherapy and chemoradiation against standard treatment alone in patients with advanced pancreatic cancer.
- Results showed no significant difference in overall survival between the two groups, with median survival times being similar (14.9 months for standard vs. 14.3 months for experimental).
- Adverse events were common in both groups, indicating that adding algenpantucel-L did not provide additional benefits in terms of survival or safety compared to standard treatment alone.