Latest news with #PD1
Medscape
4 days ago
- Health
- Medscape
Real-World Data: Adjuvant Therapy for BRAF-Mutated Melanoma
This transcript has been edited for clarity. Hello, everybody. My name is Teresa Amaral. Welcome back to this Medscape Oncology series on melanoma. Today, we'll finalize a discussion about real-world data on adjuvant therapy in patients with BRAF -mutated melanoma. We discussed the visual comparison between immunotherapy and targeted therapy using real-world data. We also discussed the benefit in terms of relapse-free survival and distant metastasis-free survival in this adjuvant setting when we compared the two therapies, showing that visual comparison seems to show a better benefit for patients receiving targeted therapy compared to immunotherapy. We looked into the differences in terms of quality of life and the toxicity profile for both therapies. Now, we will look into the last aspect that we need to discuss with our patients, which is what we do when the patients have a relapse. Obviously, it is different whether the patients have a relapse under adjuvant therapy or off adjuvant therapy. Patients who have a recurrence under adjuvant targeted therapy seem to benefit from programmed cell death protein 1 (PD-1) therapy afterward in a similar way as patients who had PD-1 monotherapy in stage IV and were treatment naive. Patients with recurrence under adjuvant PD-1 therapy do not seem to benefit from continuing PD-1 therapy, but they might benefit from other immunotherapies, such as ipilimumab or the combination of ipilimumab plus PD-1. We have other real-world data, which we've discussed in the episodes before, on where to go in terms of immunotherapy judgment setting. Even if we have a prolongation in terms of relapse-free survival or metastasis-free survival, when we look into overall survival data from real-world studies, we don't see a benefit in either of the two cohorts, one before introducing adjuvant therapy and another after introducing adjuvant therapy. This is also something that we need to discuss with our patients when we propose adjuvant therapy. The paper I mentioned before is an indirect comparison, and of course, it needs to be read as so. There are real-world data that have been analyzed, but obviously, we cannot change the data and how they were analyzed. When we look into the relapse-free survival events, we need to consider that these events are dependent on the timing when the imaging evaluation was performed. If you have an imaging evaluation that was performed a little bit earlier, you might detect relapse-free survival earlier as compared to an imaging evaluation that was performed later. The criteria for including these studies in this analysis was the same, but inclusion criteria may vary in the different trials, which might lead to a bias. Another aspect that is important to retain from this analysis is that we included both patients with BRAF wild-type and BRAF -mutated melanoma, because we could not separate these as we didn't have access to raw data. We also included all patients despite the BRAF mutation subtype. We didn't know if the patients were BRAF V600E or K, although the majority were reported as having BRAF V600E. We also were not able to analyze the data based on the substage — so stage IIIA to IIID. We included all the patients as stage III, but not the substage. Although the median follow-up time is long, it might not be long enough to capture all the events in the adjuvant setting. We probably need an update of this work in the near future. We were unable to exclude a couple of patients that were stage IV with no evidence of disease that were included in the different publications because we didn't have access to the raw data. We didn't perform any statistical comparison because of the differences in terms of the publications that we selected. The comparison was visually performed based on the formula that I mentioned in the first episode of this series. We have some advantages from this analysis. One is the number of patients, where more than 3600 patients were included. We included analyses that started around 2018, which means that, for the majority of the patients, they would have had access to PD-1 therapies or PD-1-based therapies as in the modern era if they had progressive disease or a recurrence. We don't know if this is the case for all the patients included in the analysis. Finally, grouping all the analyses and doing this digitalization using this visual comparison is obviously, I would say, an advantage. Another advantage is the fact that we used weighted average calculations to produce these Kaplan-Meier curves, showing that there is a concordance among the different works that we selected for this analysis. In conclusion, I would say that, based on this real-world analysis, targeted therapy seems to have a better outcome when we look into relapse-free survival and distant metastasis-free survival in stage III. Targeted therapy has a different profile from immunotherapy, and this needs to be discussed with the patients, especially when we look into long-term toxicity. Also, the impact in terms of quality of life between these two therapies seems to be different, and this needs to be taken into consideration when we discuss this with our patients. With that, I'll finish this three-episode series. I look forward to your comments and to our next series together. Enjoy your day.
Medscape
26-05-2025
- Health
- Medscape
SCD Impairs T-Cell Function in Cancer
Sickle cell disease (SCD) altered CD8+ T-cell chromatin architecture, triggering ferroptosis and weakening antitumor immunity. Hydrogen sulfide (H2S) treatment restored chromatin interactions and enhanced immune responses, improving immunotherapy effectiveness in renal medullary carcinoma. METHODOLOGY: Researchers analyzed CD8+ T cells from peripheral blood mononuclear cells of healthy donors and patients with SCD, examining chromatin architecture changes through Hi-C technology and DNA fluorescence in situ hybridization (FISH). Analysis included CD34+ hematopoietic stem cell–engrafted humanized mice with high human leukocyte engraftment showing over 75% human CD45+ leukocytes for RMC2C1 cell implantation studies. Treatment protocols involved administration of 10 mg/kg GYY4137 intraperitoneally twice weekly for 3 weeks, followed by anti–programmed cell death 1 (PD-1) antibody treatment at 200 μg per mouse twice weekly. TAKEAWAY: CD8+ T cells from patients with SCD exhibited reduced SLC7A11 expression and increased lipid peroxidation compared with healthy control individuals, with a significantly decreased H2S concentration in serum samples ( P < .0001). < .0001). GYY4137 treatment restored SLC7A11 chromatin interactions and enhanced immune function, with combination therapy showing improved antitumor efficacy ( P < .0001). < .0001). Analysis revealed reduced long-range chromatin interactions in SCD CD8+ T cells, particularly affecting genes involved in H2S biosynthesis including CBS and CTH . and . Treatment with GYY4137 and anti–PD-1 increased tumor-resident CD8+ T-cell infiltration ( P < .0001) and boosted cytotoxic activity through higher percentages of granzyme B+ CD8+ T cells. IN PRACTICE: 'Our study revealed that SCD altered CD8+ T cell 3D genome architecture, triggering ferroptosis and weakening antitumor immunity, thereby promoting tumor growth. Using murine and humanized SCD models, we found that disrupted chromosomal interactions in CD8+ T cells reduced the expression of antiferroptotic genes, including SLC7A11 and hydrogen sulfide (H2S) biogenesis genes, thereby increasing susceptibility to ferroptosis. Therapeutic restoration of H2S concentration in SCD mice rescued SLC7A11 expression, mitigated ferroptosis, and enhanced immune and antitumor responses,' the authors of the study wrote. SOURCE: This study was led by Zilong Zhao, The University of Texas MD Anderson Cancer Center in Houston. It was published online on May 12 in Immunity . LIMITATIONS: According to the authors, while Hi-C and DNA FISH analyses revealed chromatin interaction changes in CD8+ T cells under SCD conditions, altered T-cell subtypes and states may contribute to these findings. The researchers noted that while this study highlights SCD's impact on ferroptosis and chromatin architecture, other tumor microenvironment–related factors remain to be examined. Additionally, the use of peripheral blood mononuclear cell–derived humanized mice may limit insights into early immune development and influence the robustness of tumor growth differences. DISCLOSURES: This study was supported by grants from National Institutes of Health, Cancer Prevention and Research Institute of Texas, and Department of Defense. Pavlos Msaouel received funding from Gateway for Cancer Research, the Kidney Cancer Association, the V Foundation, and the MDACC Physician-Scientist Award. Additional disclosures are noted in the original article.
Business Upturn
22-05-2025
- Business
- Business Upturn
Boehringer Ingelheim to present early clinical evidence of innate immune modulation and anti-tumor activity via SIRPα blockade in two ongoing trials at ASCO 2025
· BI 765063 in combination with programmed cell death-1 (PD1) inhibitor antibody ezabenlimab + cetuximab demonstrated a well-tolerated safety profile and potentially promising efficacy signals as second-line treatment in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). · Next generation SIRP α inhibitor BI 770371 was shown to be well tolerated alone and in combination with PD1 inhibitor ezabenlimab in a dose escalation trial in patients with advanced solid tumors. BI 770371 is currently being further investigated in a Phase 1b study in first-line patients with R/M HNSCC. Ingelheim, Germany, 22 May 2025 – Boehringer Ingelheim today announced that new clinical data from two early-stage trials targeting the signal regulatory protein α (SIRPα) innate immune checkpoint will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 – June 3, 2025, in Chicago, IL, USA. Advertisement In a Phase 1b study conducted by Boehringer, its potential, first-in-class SIRPα monoclonal antibody, BI 765063, demonstrated a manageable safety profile as well as preliminary signs of immune activation and additive antitumor activity when combined with PD-1 inhibitor ezabenlimab and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).[1] Additionally, in an open-label, Phase I trial conducted by Boehringer, its next-generation SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab, was shown to be well tolerated in patients with advanced solid tumors. There were no dose-limiting toxicities in either treatment arm, and the maximum tolerated dose was not reached in either group.[2] 'The preliminary results from these early-stage programs are encouraging and further strengthen Boehringer's robust immuno-oncology pipeline aimed at accelerating next-generation cancer therapies to address high unmet patient needs,' said Mike Akimov, Head of Medicine, Therapy Area Oncology at Boehringer Ingelheim. 'Boehringer is developing various complementary approaches to activate the immune system against cancer cells and SIRPα blockade paired with a PD-1 inhibitor is a promising strategy. We look forward to seeing if this dual activation may lead to a broader and more sustained anti-tumor response as the programs progress.' BI 765063 and BI 770371 are designed to block the 'don't eat me' signal that cancer cells use to hide from the immune system. By targeting SIRPα, these antibodies help immune cells like macrophages recognize and destroy tumor cells, bolstering the body's natural defenses.[3] Both antibodies have been developed in partnership with OSE, with Boehringer solely responsible for future clinical development and commercialization. Boehringer will move forward with the improved next generation SIRPα inhibitor antibody BI 770371, which will now be tested in a Phase 1b study. Presentation Details: Title: An Open-Label, Phase Ib Trial of the SIRPα Inhibitor BI 765063 in Combination with the PD-1 Inhibitor Ezabenlimab and Cetuximab in Patients (pts) with Head and Neck Squamous Cell Carcinoma Abstract Number: 6019 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:30am – 1:30pm CDT Title: An Open-label, Phase I Trial of the SIRPα Monoclonal Antibody, BI 770371, Alone and in Combination with the PD-1 Inhibitor Ezabenlimab in Patients with Advanced Solid Tumors Abstract Number: 2515 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:15am – 12:45pm CDT Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer Ingelheim takes a long-term perspective, embedding sustainability along the entire value chain. More than 54,500 employees serve over 130 markets to build a healthier, more sustainable and equitable tomorrow. Learn more at (Global). OSE Immunotherapeutics OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology (IO) and immuno-inflammation (I&I) that address the unmet patient needs of today and tomorrow. We partner with leading academic institutions and biopharmaceutical companies in our efforts to develop and bring to the market transformative medicines for people with serious diseases. OSE Immunotherapeutics is based between Nantes and Paris and is quoted on Euronext. Additional information about OSE Immunotherapeutics assets is available on the Company's website: Click and follow us on LinkedIn. Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. Forward-looking statements This press release contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics. They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE Immunotherapeutics' management considering its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other factors they believe to be appropriate. These forward-looking statements include statements typically using conditional and containing verbs such as 'expect', 'anticipate', 'believe', 'target', 'plan', or 'estimate', their declensions and conjugations and words of similar import. Although the OSE Immunotherapeutics management believes that the forward-looking statements and information are reasonable, the OSE Immunotherapeutics' shareholders and other investors are cautioned that the completion of such expectations is by nature subject to various risks, known or not, and uncertainties which are difficult to predict and generally beyond the control of OSE Immunotherapeutics. These risks could cause actual results and developments to differ materially from those expressed in or implied or projected by the forward-looking statements. These risks include those discussed or identified in the public filings made by OSE Immunotherapeutics with the AMF. Such forward-looking statements are not guarantees of future performance. This press release includes only summary information and should be read with the OSE Immunotherapeutics Universal Registration Document filed with the AMF on April 30, 2024, including the annual financial report for the fiscal year 2023, available on the OSE Immunotherapeutics' website. Other than as required by applicable law, OSE Immunotherapeutics issues this press release at the date hereof and does not undertake any obligation to update or revise the forward-looking information or statements. Contacts Boehringer Ingelheim OSE Immunotherapeutics Disclaimer: The above press release comes to you under an arrangement with GlobeNewswire. Business Upturn takes no editorial responsibility for the same.
Yahoo
22-05-2025
- Business
- Yahoo
Boehringer Ingelheim to present early clinical evidence of innate immune modulation and anti-tumor activity via SIRPα blockade in two ongoing trials at ASCO 2025
· BI 765063 in combination with programmed cell death-1 (PD1) inhibitor antibody ezabenlimab + cetuximab demonstrated a well-tolerated safety profile and potentially promising efficacy signals as second-line treatment in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). · Next generation SIRPα inhibitor BI 770371 was shown to be well tolerated alone and in combination with PD1 inhibitor ezabenlimab in a dose escalation trial in patients with advanced solid tumors. BI 770371 is currently being further investigated in a Phase 1b study in first-line patients with R/M HNSCC. Ingelheim, Germany, 22 May 2025 – Boehringer Ingelheim today announced that new clinical data from two early-stage trials targeting the signal regulatory protein α (SIRPα) innate immune checkpoint will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 - June 3, 2025, in Chicago, IL, USA. In a Phase 1b study conducted by Boehringer, its potential, first-in-class SIRPα monoclonal antibody, BI 765063, demonstrated a manageable safety profile as well as preliminary signs of immune activation and additive antitumor activity when combined with PD-1 inhibitor ezabenlimab and cetuximab in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).[1] Additionally, in an open-label, Phase I trial conducted by Boehringer, its next-generation SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab, was shown to be well tolerated in patients with advanced solid tumors. There were no dose-limiting toxicities in either treatment arm, and the maximum tolerated dose was not reached in either group.[2] 'The preliminary results from these early-stage programs are encouraging and further strengthen Boehringer's robust immuno-oncology pipeline aimed at accelerating next-generation cancer therapies to address high unmet patient needs,' said Mike Akimov, Head of Medicine, Therapy Area Oncology at Boehringer Ingelheim. 'Boehringer is developing various complementary approaches to activate the immune system against cancer cells and SIRPα blockade paired with a PD-1 inhibitor is a promising strategy. We look forward to seeing if this dual activation may lead to a broader and more sustained anti-tumor response as the programs progress.' BI 765063 and BI 770371 are designed to block the 'don't eat me' signal that cancer cells use to hide from the immune system. By targeting SIRPα, these antibodies help immune cells like macrophages recognize and destroy tumor cells, bolstering the body's natural defenses.[3] Both antibodies have been developed in partnership with OSE, with Boehringer solely responsible for future clinical development and commercialization. Boehringer will move forward with the improved next generation SIRPα inhibitor antibody BI 770371, which will now be tested in a Phase 1b study. Presentation Details: Title: An Open-Label, Phase Ib Trial of the SIRPα Inhibitor BI 765063 in Combination with the PD-1 Inhibitor Ezabenlimab and Cetuximab in Patients (pts) with Head and Neck Squamous Cell Carcinoma Abstract Number: 6019 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:30am – 1:30pm CDT Title: An Open-label, Phase I Trial of the SIRPα Monoclonal Antibody, BI 770371, Alone and in Combination with the PD-1 Inhibitor Ezabenlimab in Patients with Advanced Solid Tumors Abstract Number: 2515 Session Type/Title: Rapid Oral Abstract – Developmental Therapeutics – Immunotherapy Date/Time: 01 June 2025 – 11:15am – 12:45pm CDT Boehringer Ingelheim Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer Ingelheim takes a long-term perspective, embedding sustainability along the entire value chain. More than 54,500 employees serve over 130 markets to build a healthier, more sustainable and equitable tomorrow. Learn more at (Global). OSE Immunotherapeutics OSE Immunotherapeutics is a biotech company dedicated to developing first-in-class assets in immuno-oncology (IO) and immuno-inflammation (I&I) that address the unmet patient needs of today and tomorrow. We partner with leading academic institutions and biopharmaceutical companies in our efforts to develop and bring to the market transformative medicines for people with serious diseases. OSE Immunotherapeutics is based between Nantes and Paris and is quoted on Euronext. Additional information about OSE Immunotherapeutics assets is available on the Company's website: Click and follow us on LinkedIn. Intended Audiences Notice This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business. Forward-looking statements This press release contains express or implied information and statements that might be deemed forward-looking information and statements in respect of OSE Immunotherapeutics. They do not constitute historical facts. These information and statements include financial projections that are based upon certain assumptions and assessments made by OSE Immunotherapeutics' management considering its experience and its perception of historical trends, current economic and industry conditions, expected future developments and other factors they believe to be appropriate. These forward-looking statements include statements typically using conditional and containing verbs such as 'expect', 'anticipate', 'believe', 'target', 'plan', or 'estimate', their declensions and conjugations and words of similar import. Although the OSE Immunotherapeutics management believes that the forward-looking statements and information are reasonable, the OSE Immunotherapeutics' shareholders and other investors are cautioned that the completion of such expectations is by nature subject to various risks, known or not, and uncertainties which are difficult to predict and generally beyond the control of OSE Immunotherapeutics. These risks could cause actual results and developments to differ materially from those expressed in or implied or projected by the forward-looking statements. These risks include those discussed or identified in the public filings made by OSE Immunotherapeutics with the AMF. Such forward-looking statements are not guarantees of future performance. This press release includes only summary information and should be read with the OSE Immunotherapeutics Universal Registration Document filed with the AMF on April 30, 2024, including the annual financial report for the fiscal year 2023, available on the OSE Immunotherapeutics' website. Other than as required by applicable law, OSE Immunotherapeutics issues this press release at the date hereof and does not undertake any obligation to update or revise the forward-looking information or statements. Contacts Boehringer Ingelheim Linda Ruckel +1 203-791-6672 Reinhard Malin +49 (6132) OSE Immunotherapeutics Fiona Sylvie Détry French Media Contact FP2COM Florence Portejoie fportejoie@ +33 6 07 768 283 U.S. Media Contact Rooney Partners LLCKate Barrettekbarrette@ +1 212 223 0561 [1] An open-label, phase Ib trial of the SIRPα inhibitor BI 765063 in combination with the PD-1 inhibitor ezabenlimab and cetuximab in patients (pts) with head and neck squamous cell carcinoma. - ASCO [1] An open-label, phase I trial of the SIRPα monoclonal antibody, BI 770371, alone and in combination with the PD-1 inhibitor ezabenlimab in patients with advanced solid tumors. - ASCO [3] Lopez-Yrigoyen, M., et al. (2017). Anti-SIRPα antibody immunotherapy enhances neutrophil and macrophage antitumor activity. Proceedings of the National Academy of Sciences, 114(33), 201710877. Error while retrieving data Sign in to access your portfolio Error while retrieving data Error while retrieving data Error while retrieving data Error while retrieving data
Globe and Mail
20-05-2025
- Business
- Globe and Mail
Pfizer Buys Rights to PD-1 & VEGF Inhibitor From China Biotech
Pfizer PFE announced that it is in-licensing global development and commercialization rights, ex-China, to SSGJ-707, a bispecific antibody targeting PD-1 and VEGF, from Chinese biotech, 3SBio. 3SBio is already developing SSGJ-707 in China for non-small cell lung cancer ('NSCLC'), metastatic colorectal cancer, and gynecological tumors, with the first phase III study expected to begin this year. Unlike the currently available marketed products, which target only the PD-1 protein, SSGJ-707 targets two proteins, PD-1 and VEGF. The blockade of two proteins, PD-1 and VEGF, can lead to a more robust anti-tumor response, compared to targeting either pathway alone For the deal, Pfizer will make an upfront payment of $1.25 billion to 3SBio, with the latter also being entitled to milestone payments of up to $4.8 billion as well as tiered double-digit royalties on sales of SSGJ-707, if approved. Pfizer will also make an equity investment of $100 million in 3SBio upon close, subject to an agreement. Pfizer also retains an option for rights to commercialization in China. The transaction is expected to be closed in the third quarter. Pfizer's stock has declined 10.2% so far this year compared with a decrease of 4.0% for the industry. SMMT's Dual PD-1/VEGF Inhibitor Summit Therapeutics SMMT is also developing a dual PD-1 and VEGF inhibitor, ivonescimab, in collaboration with China-based Akeso. The company acquired an exclusive license from Akeso in 2022 to develop and market the drug in the United States, Canada, Europe and Japan. Ivonescimab is already approved only in China to treat EGFR-mutated, locally advanced or metastatic non-squamous NSCLC. In 2024, Summit Therapeutics reported positive data from a phase III study (conducted in China by partner Akeso) in patients with locally advanced or metastatic NSCLC, in which ivonescimab, outperformed Merck 's MRK blockbuster PD-L1 inhibitor, Keytruda. Summit believes ivonescimab has the potential to replace Merck's Keytruda as the next standard of care across multiple NSCLC settings. PFE's Zacks Rank Pfizer currently has a Zacks Rank #2 (Buy). You can see the complete list of today's Zacks #1 Rank (Strong Buy) stocks here. 5 Stocks Set to Double Each was handpicked by a Zacks expert as the #1 favorite stock to gain +100% or more in 2024. While not all picks can be winners, previous recommendations have soared +143.0%, +175.9%, +498.3% and +673.0%. Most of the stocks in this report are flying under Wall Street radar, which provides a great opportunity to get in on the ground floor. Today, See These 5 Potential Home Runs >> Want the latest recommendations from Zacks Investment Research? Today, you can download 7 Best Stocks for the Next 30 Days. Click to get this free report Pfizer Inc. (PFE): Free Stock Analysis Report Merck & Co., Inc. (MRK): Free Stock Analysis Report Summit Therapeutics PLC (SMMT): Free Stock Analysis Report
