Latest news with #Avelumab
Iraqi News
3 days ago
- Health
- Iraqi News
Combination therapy extends survival in advanced skin cancer, trial finds
In patients with an advanced type of skin cancer called cutaneous squamous cell carcinoma (cSCC), those who received the combination of the immunotherapy drug avelumab and targeted agent cetuximab had almost four times longer median progression-free survival compared to patients who received avelumab alone, according to the results of a phase 2 trial presented today at the American Society of Clinical Oncology (ASCO) meeting and concurrently published in the Journal of Clinical Oncology. "It is both an honor and humbling to develop clinical trials that can be potential options for our patients," said lead author and study chair for the trial, Dan Zandberg, M.D., associate professor of medicine at the University of Pittsburgh and medical oncology co-leader of the head and neck cancer program at UPMC Hillman Cancer Center. "My hope is that the insights we made with this trial will lead to additional studies that can ultimately bring a new immunotherapy-based combination into standard of care for patients with advanced cSCC." cSCC is a common type of skin cancer with about 1.8 million cases diagnosed in the U.S. each year. About 95% of cSCCs are detected early and can be treated with minor surgery. But in rare cases, patients will go on to develop advanced cSCC, which includes locally advanced tumors that cannot be surgically removed and metastatic disease. At this point, the prognosis is poor and treatment is focused on extending survival, not cure. Zandberg developed the Alliance A091802 (NCT03944941) phase 2 trial in collaboration with the Alliance for Clinical Trials in Oncology through the National Cancer Institute's (NCI) National Clinical Trials Network. This trial, which was open nationwide, included 57 patients with advanced cSCC. UPMC Hillman was the leading site for patient recruitment, with some of those patients recruited and treated at its network of more than 70 community cancer centers. Twenty-nine patients received avelumab and cetuximab and 28 received avelumab alone. Because the trial had a crossover design, nine patients in the avelumab group whose cancer progressed switched to the combination group. Avelumab is an immune checkpoint inhibitor drug that targets a protein found on cancer cells called PD-L1. When PD-L1 binds to a receptor on T cells called PD-1, it acts like a brake, slowing down the cancer-killing activity of T cells. Avelumab and other anti-PD-1/PD-L1 therapies release those brakes. Cetuximab is a monoclonal antibody that targets EGFR (epidermal growth factor receptor), a protein that plays a critical role in tumor cell growth, proliferation and survival and which is often found in high levels on cSCC cells. It activates natural killer cells, which help fight tumors, and can also activate dendritic cells, which can then stimulate T cells. Previous research done at UPMC Hillman by Robert Ferris, M.D., Ph.D. and his lab helped reveal cetuximab's effect on the immune system. "The rationale for the combination is that avelumab and other anti-PD-1/PD-L1 therapies have been shown to take the foot off the brake of the immune system, while cetuximab is pressing on the gas pedal—trying to work together to make the immune system go faster and attack the tumor," said Zandberg. "What's exciting is that in this trial the efficacy of the combination suggests that the two drugs were synergistic, rather than just additive." The study showed that the primary endpoint of progression-free survival was significantly higher in patients who received avelumab plus cetuximab with a median of 11 months compared to just 3 months in patients who received avelumab alone. Even though avelumab and cetuximab led to an almost quadrupling of median progression-free survival compared to avelumab alone, the trial does not support this combination as a standard treatment for patients. That's because since the trial was launched, two other anti-PD-1/PD-L1 therapies—cemiplimab and pembrolizumab—have been approved and had higher efficacy than avelumab in trials in patients with cSCC. However, the trial represents the first completed prospective randomized comparison of cetuximab plus blockade of the PD-1/PD-L1 pathway versus blockade of that pathway alone in cSCC or head and neck cancer, where this combination has also shown promise. The trial provides valuable information for future trials. "These findings highlight the potential benefits of combining cetuximab with an anti-PD-1/PD-L1 therapy and points to the importance of additional clinical trials combining either standard of care pembrolizumab or cemiplimab with cetuximab as a potential way to improve patient outcomes in advanced cSCC," said Zandberg. Notably, patients in the crossover arm had a similar progression-free survival to those who received the combination from the start. Currently, if a patient fails immunotherapy with pembrolizumab or cemiplimab, they switch to cetuximab or chemotherapy. But this trial suggests that continuing immunotherapy and adding cetuximab could be more beneficial.
Yahoo
26-03-2025
- Business
- Yahoo
Vaximm AG, an OSR Company, Announces Results from Phase 2a Trial of VXM01 and Avelumab Combination Therapy in Glioblastoma
Results from Phase 2a Trial demonstrate a good safety and tolerability profile of VXM01 and Avelumab Combination Therapy in Glioblastoma, supporting further investigation of VXM01 BASEL, Switzerland, March 26, 2025 /PRNewswire/ -- Vaximm AG, a subsidiary of OSR Holdings, Inc. and a pioneering biotechnology company focused on developing innovative immunotherapies, today announced final data from the successful conclusion of its open-label Phase 2a clinical trial assessing the safety and tolerability of VXM01, an investigational oral anti-VEGFR-2 vaccine, in combination with avelumab (PD-L1 inhibitor) in patients with recurrent glioblastoma (GBM). The trial was part of a collaboration with Merck KGaA, Darmstadt, Germany. Key results and observations: The VXM01-avelumab combination therapy was generally well-tolerated, with the majority of safety events being mild to moderate in severity. These safety and tolerability data are in-line with previously reported data on avelumab alone with no additional safety signals for the combination of VXM01 and avelumab. No serious adverse events (SAEs) were attributed to VXM01, while 9 of 11 (81.8%) were related to the target disease, underscoring the well manageable safety profile of this combination therapy in a frail patient population. The non-resected patient cohort showed a 12.0% objective response rate (ORR). 12.0% of these patients showed a partial remission and 4.0% had stable disease. This suggests that, with further investigation, VXM01 in combination with PD-L1 inhibition (e.g. avelumab) could offer meaningful clinical benefit for this challenging patient population. In resected patients, the overall survival (OS) ranged from 2.2 to 46.5 months, highlighting the variability in response and the need for additional studies to determine optimal treatment regimens for specific subgroups of GBM patients. Despite the small size of this open-label trial (n=25), the observed median time to progression of 2.7 months (95% CI: 2.7 – 2.7, range 0.3 - 22.1 months), and median OS of 11.1 months (95% CI: 8.5 – 16.3, range 3.8- 38.2 months), are encouraging initial results in the context of prognosis for patients with recurrent glioblastoma, reported to have a median PFS of 1.5 to 6 months and median OS of 2 to 9 months.(Birzu et al. 2020) Decreased tumor size was observed in responding patients independent of tumor size at baseline, supporting the expectation that VXM01 vaccine treatment may be effective in patients with larger sized tumors as well as patients with early-stage cancer or very small tumors. Exploratory biomarker investigations identified potential predictive and pharmacodynamic biomarkers of a VXM01-mediated tumor response Moving Forward: The reported safety and tolerability data, together with early indications for the potential relevance of a VXM01dependent, VEGFR-2 specific immune response in GBM therapy warrant further study. "The completion of this Phase 2a study is a significant milestone for Vaximm AG, as it provides strong evidence that VXM01, in combination with avelumab is generally well-tolerated in patients with recurrent glioblastoma," said Dr. Constance Hoefer, CEO of Vaximm AG. "We are encouraged by these early results and the potential to improve outcomes for patients with this aggressive cancer. We remain committed to advancing VXM01 as a key therapeutic candidate for the treatment of glioblastoma, other cancers and other diseases where VXM01 may have positive impact on treatment outcomes" About VXM01: VXM01 is an oral T-cell immunotherapy that is designed to activate T-cells to attack the tumor vasculature and, in several tumor types, attack cancer cells directly. It is based on a live attenuated, safe, orally available bacterial vaccine strain, which is modified to carry vascular endothelial growth factor receptor-2 (VEGFR2) as the target gene. VXM01 stimulates the patient's immune system to activate VEGFR2-specific, cytotoxic T-cells (so-called killer cells). These immune killer cells then actively destroy cells in the tumor vasculature, leading to an increased infiltration of various immune cells into the tumor. In several tumor types, including brain cancer, VEGFR2 is highly over-expressed on the cancer cells themselves. In preclinical studies, a murine analog VXM01 vaccine showed broad anti-tumor activity in different tumor types. This activity was linked to a VEGFR2-specific T-cell response and was accompanied by the destruction of the tumor vasculature and increased immune cell infiltration. In a Phase I double-blind, randomized, placebo-controlled study in 71 patients with advanced pancreatic cancer, VXM01 appeared to be safe and well tolerated and led to the activation of VEGFR2-specific cytotoxic T-cells, which was associated with significantly improved patient survival. Clinical activity in terms of objective responses and survival has been observed in recurrent glioblastoma. About Vaximm AG: Vaximm AG is a pioneering biotechnology company focused on developing innovative immunotherapies. Through innovative approaches, Vaximm aims to unlock the potential of cancer vaccines and immune-oncology therapies to address the unmet needs of patients suffering from various types of cancer. For more information about Vaximm, please visit About OSR Holdings Inc: OSR Holdings, Inc. (NASDAQ: OSRH) is a global healthcare company dedicated to advancing healthcare outcomes and improving the quality of life for people and their families. OSR aims to build and develop a robust portfolio of innovative and potentially transformative therapies and healthcare solutions. Its current operating businesses (through three wholly-owned subsidiaries) include (i) developing oral immunotherapies for the treatment of cancer ("Vaximm"), (ii) developing design-augmented biologics for age-related and other degenerative diseases ("Darnatein") and (iii) neurovascular intervention medical device and systems distribution in Korea ("RMC"). OSR's vision is to acquire and operate a portfolio of innovative healthcare related companies globally. Contact: Vaximm AGEmail: ir@ Website: View original content to download multimedia: SOURCE OSR Holdings Inc. Sign in to access your portfolio
