Latest news with #nivolumab
Medscape
6 days ago
- Business
- Medscape
Adjuvant Nivolumab + CRT Improves DFS in HNSCC
Adding nivolumab (Opdivo) to standard-of-care cisplatin radiotherapy (CRT) after surgery for locally advanced head and neck squamous cell carcinoma (HNSCC) in patients at a high risk for relapse reduced the risk for recurrence, as per a phase 3 trial. This new therapeutic option 'improved high-risk locally advanced squamous cell carcinoma of the head and neck,' said study author Jean Bourhis, MD, PhD, during a press conference at American Society of Clinical Oncology (ASCO) 2025. Postoperative nivolumab added to standard-of-care adjuvant CRT 'could be proposed as a new standard treatment for the first time in two decades,' said Bourhis, MD, PhD, of Lausanne University Hospital in Lausanne, Switzerland, while reporting results of NIVOPOSTOP (GORTEC 2018-01) during the press conference. Agreeing with Bourhis' characterization of the therapeutic regimen followed in the new trial, Stuart Wong, MD, said NIVOPOSTOP 'represents a potential new standard,' in his comments as discussant of the results at the meeting's Plenary Session. As immunotherapy for head and neck cancers evolve, so must the approach to managing these patients, said Wong, who is director of the Center for Disease Prevention Research at the Medical College of Wisconsin in Milwaukee. 'In a world where neoadjuvant and adjuvant anti–PD-1 [programmed cell death 1] are options for patient care, a multidisciplinary tumor board discussion is optimal and should include individual patient and social factors, as well as consideration of individual tumor growth dynamic,' Wong said. 'The NIVOPOSTOP study presents a major turning point,' he added. 'However, we face many steep obstacles ahead of us, foremost among these the completion of ongoing studies.' Study Design and Results The study enrolled 680 patients aged 75 years or younger with HNSCC who had complete macroscopic surgical resection of stage III or IV cancer. Half the patients were either smokers or heavy smokers, and the most common tumor site was the oral cavity. About 80% of patients had either stage IVA or IVB disease. After surgical resection, patients were randomized to one of the two regimens. The treatment group received one dose of 240 mg nivolumab, followed by a dose of 360 mg nivolumab every 3 weeks plus standard-of-care 100 mg/m2 cisplatin every 3 weeks and 66 grays (Gy) of intensity-modulated RT (IMRT), followed by six doses of 480 mg nivolumab over 4 weeks. The control group received 100 mg/m2 cisplatin every 3 weeks and IMRT 66 Gy. The rate of 3-year disease-free survival in the nivolumab plus CRT group was 63.1% vs 52.5% in the control group ( P = .034), representing a 24% improvement, Bourhis said. The nivolumab plus CRT group also had a 37% reduced risk for cumulative incidence of locoregional relapses alone at 3 years, he added. Compliance rates were similar between both groups. For example, RT compliance rates over 55 days were 95% for nivolumab plus CRT and 97% for CRT. The proportion of patients experiencing more serious side effects in the 100 days following treatment was higher in the nivolumab plus CRT group than in the control group (13.1% vs 5.6%). The most common grade 4 adverse events in both groups were neutropenia and lymphocytopenia. Most treatment-related adverse events were less serious grade 1 or 2 events and were related to chemoradiotherapy in both groups. The nivolumab group had 'a slight increase' in renal toxicity (24% vs 15%) and 'a more pronounced increase' in thyroid disorders (20% vs 2%), Bourhis said. Evidence Is Growing NIVOPOSTOP adds to a body of evidence supporting the use of adjuvant immunotherapy in difficult-to-treat disease, Glenn Hanna, MD, director of the Center for Cancer Therapeutic Innovation at Dana-Farber Cancer Institute in Boston, said at the press conference. He cited results from the KEYNOTE-689 trial, reported in April at American Association for Cancer Research Annual Meeting 2025, in which patients with HNSCC were given perioperative neoadjuvant pembrolizumab followed by adjuvant pembrolizumab. 'It brings us into a space where we were with kidney cancers and with melanoma, to say what is the right sequence of immunotherapy?' Hanna said. He noted that NIVOPOSTOP and KEYNOTE-689 both reported similar outcomes. 'So do you give the immunotherapy first, or do we wait and do it in the adjuvant setting?' he said. Based on Bourhis' research, 'they are comparable.' He added, 'I think now immunotherapy will be here and present for our head and neck patients undergoing cancer resection.' NIVOPOSTOP received support from Bristol Myers Squibb and GORTEC. Bourhis reported having financial relationships with AstraZeneca, Bristol Myers Squibb, Merck Serono, and Merck Sharpe and Dohme. Hanna reported having relationships with Actuate Therapeutics, Bicara Therapeutics, Boxer Capital, Bristol Myers Squibb, Coherus BioSciences, Elevar Therapeutics, Genentech, Greywolf Therapeutics, ImmunityBio, InhibRx, KSQ Therapeutics, Kura Oncology, Merck, Naveris, Nextech Invest, PDS Biotechnology, Regeneron, Remix Therapeutics, Replimune, Secura Bio, and Surface Oncology. Wong reported receiving research funding from Hookipa Pharma, Merck, and Novartis.
Yahoo
01-06-2025
- Business
- Yahoo
Replimune Presents New Analyses from the IGNYTE Study of RP1 plus Nivolumab in Anti-PD1 Failed Melanoma at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting
- RP1 plus nivolumab generated robust responses in both injected and non-injected lesions - - Deep/visceral injections, including into the liver and lung, resulted in numerically higher rates of response compared to superficial injections only and were generally well tolerated - WOBURN, Mass., June 01, 2025 (GLOBE NEWSWIRE) -- Replimune Group, Inc. (NASDAQ: REPL), a clinical stage biotechnology company pioneering the development of novel oncolytic immunotherapies, today presented two posters highlighting data updates for RP1 (vusolimogene oderparepvec) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 30-June 3 in Chicago. 'The new analyses we presented from the IGNYTE clinical trial of RP1 plus nivolumab in anti-PD-1 failed melanoma confirms our belief in the systemic activity of the combination, and also shows robust responses in injected liver and lung lesions with an acceptable safety profile,' said Kostas Xynos, M.D., Chief Medical Officer of Replimune. 'Additional data also presented at the meeting shows that RP1 can be handled safely with no additional biosafety protocols required confirming that standard disinfection procedures are sufficient for clean up.' Key findings are outlined below. Poster Presentation: Response analysis for injected and non-injected lesions and the safety and efficacy of superficial and deep RP1 injection in the registrational cohort of anti-PD-1-failed melanoma patients of the IGNYTE trial (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 20; Abstract: 9537) The poster included an analysis from the IGNYTE clinical trial of RP1 plus nivolumab in the cohort of anti-PD-1 failed melanoma patients (n=140). In the trial, the objective response rate (ORR) was 32.9% using RECIST 1.1. The complete response rate was 15.0% and landmark overall survival (OS) rates at 1, 2, and 3 years were 75.3%, 63.3%, and 54.8% respectively. Median OS has not been reached. Patients experienced numerically higher objective response rates after receiving deep injections (± superficial) compared with superficial injections only. Deep responses were observed in injected and non-injected lesions. The ORR by injection type using RECIST 1.1 was 29.8% when only superficial lesions were injected, 42.9% for deep/visceral plus superficial injections injected, and 40.9% when only deep/visceral lesions were injected. There was a ≥30% reduction in 93.6% (73/78) of injected lesions and 79.0% (94/119) of non-injected lesions. The kinetics of response were similar in injected vs non-injected lesions. Of the non-injected visceral organ lesions in responding patients, 96.2% (50/52) showed reduction from baseline, with 65.4% reduced by ≥30%. RP1 injections directly into the lung and liver were generally well tolerated and resulted in few organ-specific adverse events that were easily managed. Liver and lung injections had a tolerable safety profile. No bleeding events were reported after liver injection. Lung injections were associated with low rates of pneumothorax events, which were typically of low grade and manageable. Overall, these data support the safety and efficacy of deep/visceral injections and demonstrate the development of a robust systemic anti-tumor response following treatment with RP1 plus nivolumab. Poster Presentation: Biosafety analysis from the skin cancer cohorts in the IGNYTE clinical trial of RP1 (Track: Melanoma/Skin Cancers; June 1, 2025, 9:00 am – 12:00 pm CDT; Location: Hall A, Board 17; Abstract: 9534) RP1 was assessed in various samples taken from patients. This demonstrated that RP1 DNA is primarily detected at the injection site, consistent with RP1 replication in the tumor, and much more rarely on dressings, in blood, on mucous membranes or in urine. In all cases, live RP1 was only rarely if ever detected, demonstrating that while residual RP1 DNA may be present, this does not indicate the presence of live RP1 There were no systemic herpetic infections in patients or reports of HSV-1 infections in contacts. RP1 is completely neutralized using standard disinfectants within 30 seconds of contact, confirming that standard disinfection procedures are sufficient for RP1 clean-up. Collectively these data demonstrate that the likelihood of transmission of RP1 to patients' contacts or into the external environment is minimal, with no transmission having been reported to date. Both posters will be available on the Company website under Events and Presentations. About RP1RP1 is Replimune's lead product candidate and is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. About RP2RP2 is based on a proprietary strain of herpes simplex virus engineered and genetically armed with a fusogenic protein (GALV-GP-R-) and GM-CSF intended to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response. RP2 additionally expresses an anti-CTLA-4 antibody-like molecule, as well as GALV-GP-R- and GM-CSF. RP2 is intended to provide targeted and potent delivery of these proteins to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic-immune-based efficacy on tumors and limiting off-target toxicity. About ReplimuneReplimune Group, Inc., headquartered in Woburn, MA, was founded in 2015 with the mission to transform cancer treatment by pioneering the development of novel oncolytic immunotherapies. Replimune's proprietary RPx platform is based on a potent HSV-1 backbone intended to maximize immunogenic cell death and the induction of a systemic anti-tumor immune response. The RPx platform is designed to have a unique dual local and systemic activity consisting of direct selective virus-mediated killing of the tumor resulting in the release of tumor derived antigens and altering of the tumor microenvironment to ignite a strong and durable systemic response. The RPx product candidates are expected to be synergistic with most established and experimental cancer treatment modalities, leading to the versatility to be developed alone or combined with a variety of other treatment options. For more information, please visit Forward Looking StatementsThis press release contains forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, including statements regarding the design and advancement of our clinical trials, the timing and sufficiency of our clinical trial outcomes to support potential approval of any of our product candidates, the regulatory review process and timing of potential product approval, our goals to develop and commercialize our product candidates, patient enrollments in our existing and planned clinical trials and the timing thereof, and other statements identified by words such as 'could,' 'expects,' 'intends,' 'may,' 'plans,' 'potential,' 'should,' 'will,' 'would,' or similar expressions and the negatives of those terms. Forward-looking statements are not promises or guarantees of future performance, and are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in such forward-looking statements. These factors include risks related to our limited operating history, our ability to generate positive clinical trial results for our product candidates, the costs and timing of operating our in-house manufacturing facility, the timing and scope of regulatory approvals, the availability of combination therapies needed to conduct our clinical trials, changes in laws and regulations to which we are subject, competitive pressures, our ability to identify additional product candidates, political and global macro factors including the impact of the coronavirus as a global pandemic and related public health issues and the Russian-Ukrainian and Israel-Hamas political and military conflicts, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q and other reports we file with the Securities and Exchange Commission. Our actual results could differ materially from the results described in or implied by such forward-looking statements. Forward-looking statements speak only as of the date hereof, and, except as required by law, we undertake no obligation to update or revise these forward-looking statements. Investor InquiriesChris BrinzeyICR Media InquiriesArleen GoldenbergReplimune917.548.1582 media@ in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
Medscape
23-05-2025
- Health
- Medscape
Can Nivolumab Maintain AML Remission?
In a randomized phase 2 study of 79 patients with acute myeloid leukemia (AML) in first complete remission, nivolumab maintenance therapy did not improve progression-free survival (13.2 vs 10.9 months) or overall survival (53.9 vs 30.9 months) compared with observation. Adverse events were more frequent in the nivolumab arm, with 71% experiencing grade ≥ 3 events vs 12% in the observation arm. METHODOLOGY: A multicenter, open-label, randomized phase 2 trial enrolled 79 patients with AML in first complete remission or complete remission with incomplete hematologic recovery who were not candidates for stem cell transplant. Participants were randomized to either observation or nivolumab arm (3 mg/kg intravenously every 2 weeks for 46 doses), with a median follow-up duration of 24 months. Primary endpoint was progression-free survival, defined as time to disease relapse or death, while secondary endpoints included overall survival and evaluation of adverse events. Analysis included measurement of measurable residual disease (MRD) through ultrasensitive duplex DNA sequencing in 55 patients and targeted RNA sequencing in two patients before randomization. TAKEAWAY: Median progression-free survival duration was 13.2 months (95% CI, 8.5-21.8) in the nivolumab arm vs 10.9 months (95% CI, 5.4-14.9) in the observation arm (hazard ratio [HR], 0.92; 95% CI, 0.54-1.56; P = .38). = .38). Overall survival analysis showed median survival duration of 53.9 months (95% CI, 23.4 to not estimable) in the nivolumab arm vs 30.9 months (95% CI, 14.4 to not estimable) in the observation arm (HR, 0.78; 95% CI, 0.40-1.51; P = .23). = .23). Adverse events of grade ≥ 3 occurred in 71% of nivolumab-treated patients compared with 12% of patients in the observation arm ( P < .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common. < .001), with fatigue (42%), hypertension (37%), and diarrhea (34%) being most common. MRD positive patients showed significantly higher relapse rates at 2 years (74% vs 37%; P = .046) and decreased progression-free survival (21% vs 63%; P = .032) than MRD negative patients. IN PRACTICE: 'With negative results using checkpoint inhibitors alone (or in combination with HMA [hypomethylating agent]), now in both the MRD setting and in the front line, the utility of targeting the PD1-PDL1 [programmed cell death 1–programmed death ligand 1] pathway in unselected AML appears limited…. It remains possible that further correlatives studies might identify a subset of patients with AML who may responses to immune checkpoint inhibition,' wrote the authors of the study. SOURCE: The study was led by Athalia Pyzer and Hongtao Liu, The University of Chicago in Chicago. It was published online on May 13 in Blood Advances . LIMITATIONS: According to the authors, subgroup analysis in the cohort of MRD positive patients did not demonstrate any effect of nivolumab on clinical outcomes, but these comparisons were underpowered. The researchers noted that other immune escape mechanisms, even beyond checkpoint pathways, likely contribute to the persistence of this disease. DISCLOSURES: The study was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, a University of Chicago Comprehensive Cancer Center pilot grant, the Ullman Scholar Award, and the Elsa U. Pardee Foundation. Additional disclosures are noted in the original article.
