Latest news with #nivolumab
Medscape
24-07-2025
- Business
- Medscape
FDA Declines to Approve New Melanoma Therapy
The FDA has declined to approve a new oncolytic immunotherapy, vusolimogene oderparepvec (RP1), to treat advanced melanoma. The agency recently issued a complete response letter to the company, Replimune Group, rejecting its biologics license application that sought approval for the new agent in combination with nivolumab (Opdivo) to treat adults with advanced melanoma. In the complete response letter, the FDA indicated that it can't approve the biologics license application for vusolimogene oderparepvec because the company's IGNYTE trial 'is not considered to be an adequate and well-controlled clinical investigation that provides substantial evidence of effectiveness,' Replimune explained in a press release. According to Replimune, the complete response letter also noted that the trial data 'cannot be adequately interpreted due to the heterogeneity of the patient population,' and that 'there are items related to the confirmatory trial study design which need to be addressed.' 'We are surprised by the FDA decision and disappointed for advanced melanoma patients who have limited treatment options, as highlighted by the granting of breakthrough status at the time we provided the IGNYTE primary data,' stated Sushil Patel, PhD, Replimune's chief executive officer. Vusolimogene oderparepvec is the lead product candidate for the biotech company. Patel further noted that the issues raised in the complete response letter were not 'raised by the agency in mid- and late-cycle reviews.' Additionally, he said, 'we had also aligned on the design of the confirmatory study.' The FDA's response to the biologics license application for the new agent, along with its recently announced policy requiring randomized, controlled trials for approval of COVID vaccines in healthy Americans younger than 65 years, may signal that the agency is taking a tougher stance on new drug approvals. Replimune plans to 'urgently interact with the FDA to find a path forward for the timely accelerated approval of RP1,' according to its statement. Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@ or on X @SW_MedReporter.
Medscape
21-07-2025
- Health
- Medscape
Insurance-Survival Gap Growing in Immunotherapy Era
TOPLINE: The approval of immune checkpoint inhibitors (ICIs) was associated with a significant improvement in 2-year overall survival among patients with advanced-stage melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma across all insurance types (except uninsured patients with renal cancer); however, the survival disparity between people with private insurance and those without health insurance grew. METHODOLOGY: ICIs, such as ipilimumab, nivolumab, and atezolizumab, have markedly improved survival across various cancer types; however, their high costs may limit access for patients who do not have health insurance coverage. Researchers analyzed data on 183,440 individuals (mean age, 55.5 years; 56.5% men) from the National Cancer Database who were diagnosed with stage IV melanoma (n = 12,048) between 2002 and 2019 as well as those with stage IV NSCLC (n = 152,610) or stage IV renal cell carcinoma (n = 18,782) between 2010 and 2019. The FDA approved ICI treatment for melanoma in 2011 and for NSCLC and renal cell carcinoma in 2015. At diagnosis, 65.0% of participants had private insurance, 24.1% were enrolled in Medicaid, and 10.9% were uninsured. The primary outcome was 2-year overall survival. The researchers applied a propensity score-weighted difference-in-differences approach to examine changes in 2-year overall survival before and after the relevant ICI approval among individuals with Medicaid or without health insurance vs those with private coverage. TAKEAWAY: Among patients with stage IV melanoma, 2-year overall survival rates increased in the ICI era across all insurance types but not to the same degree: uninsured from 16.2% to 28.3%, Medicaid from 14.1% to 29.6%, and private insurance from 28.7% to 46.0%. The survival gap between the privately insured and uninsured widened significantly by 6.1 percentage points after adjusting for comorbidities and sociodemographic characteristics. Similarly, overall survival improved among patients with stage IV NSCLC, but the disparity between uninsured and privately insured patients increased by 1.3 percentage points, after adjustment. For renal cell carcinoma, the disparity between uninsured and privately insured patients increased by 5.8 percentage points but was not significant. After excluding data for the first post-approval year to account for lags in uptake, survival disparities between uninsured and privately insured patients widened significantly for all three cancer types: stage IV melanoma (5.0 percentage points), NSCLC (2.2 percentage points), and renal cell carcinoma (6.0 percentage points). Survival differences between Medicaid-insured and privately insured patients did not change significantly across all cancer types post-ICI approval. IN PRACTICE: In this cross-sectional study, the introduction of ICIs was associated with improved survival across insurance types, but preexisting disparities between privately insured and uninsured individuals worsened. 'Programs that reduce barriers to care, such as expanding access to health insurance coverage, providing comprehensive financial assistance to people without health insurance coverage, and making new treatments more affordable, may help to mitigate these disparities,' the authors concluded. SOURCE: This study, led by Jingxuan Zhao, PhD, MPH, of the American Cancer Society, Atlanta, was published online in JAMA Network Open. LIMITATIONS: Health insurance was only measured at cancer diagnosis, with no information on subsequent coverage changes. Additionally, the study was limited to examining all-cause mortality due to the lack of data on cancer-specific mortality in the database. The database lacked information on specific treatment agents and the percentage of patients who actually received ICIs is unknown, limiting the analysis to population-level rather than direct treatment effects. DISCLOSURES: The authors did not disclose any funding information. Some authors reported receiving grants or honoraria from various sources, outside the current work. Additional disclosures are noted in the original article. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
16-07-2025
- Health
- Medscape
Fact or Fiction: Bladder Cancer
Recent advances in immunotherapy, genomic profiling, and bladder-sparing techniques have begun to reshape diagnostic algorithms and treatment strategies across disease stages, from non-muscle-invasive to metastatic bladder cancer. Immunotherapies targeting PD-1 and PD-L1 have shown durable responses in certain subsets of patients, while next-generation sequencing helps guide decisions by identifying actionable mutations and molecular subtypes. Additionally, minimally invasive surgical techniques, improvements in intravesical therapies, and novel surveillance tools such as urinary biomarkers contribute to a more personalized, risk-adapted approach. As the field moves toward more integrated, multidisciplinary care, clinicians and care teams must stay abreast of these innovations to ensure optimal outcomes, improved quality of life, and equitable access to cutting-edge therapies. Checkpoint inhibitors such as atezolizumab, nivolumab, and pembrolizumab have been approved for patients with advanced or metastatic urothelial carcinoma, especially those ineligible for cisplatin-based chemotherapy or with disease progression after platinum therapy. These agents work by targeting PD-1 or PD-L1 pathways to enhance the immune system's ability to fight cancer. In recent years, nivolumab was approved for use in combination with cisplatin and gemcitabine as first-line treatment for unresectable or metastatic urothelial carcinoma, marking a major shift toward integrating immunotherapy earlier in treatment algorithms. Learn more about immunotherapy for bladder cancer. Cigarette smoking is the leading risk factor for bladder cancer, responsible for approximately 50% of all cases. Smokers are twice as likely to develop bladder cancer than nonsmokers. Smoking cessation significantly reduces risk over time, though former smokers remain at elevated risk compared to never-smokers. Occupational exposures, such as to benzidine and beta-naphthylamine, are also important, especially for long-term workers in underregulated environments. However, these exposures account for a smaller percentage of overall cases. Environmental exposures are increasingly being realized as a cause for bladder cancer. Pesticides and contaminated drinking water are concerns. Learn more about bladder cancer etiology. The majority of NMIBC cases are managed conservatively, starting with transurethral resection of bladder tumor (TURBT). At recurrence, however, intravesical therapy with instilled chemotherapy drugs, Bacillus Calmette-Guérin (BCG), and immediate radical cystectomy are options that should be discussed. Radical cystectomy is generally reserved for patients who are unresponsive to or who have high-grade T1 lesions with associated carcinoma in situ, lymphovascular invasion, or variant histology. Bladder preservation is a cornerstone of treatment for low- and intermediate-risk patients with NMIBC, aiming to maintain quality of life while achieving cancer control. Surveillance through periodic cystoscopy and urinary cytology is essential to detect recurrences, which are common. Learn more about treatment for NMIBC. Although several urinary biomarkers (eg, NMP22, UroVysion FISH, Cxbladder, bladder tumor antigen tests) are available, they have not replaced cystoscopy, which remains the cornerstone of surveillance. Cystoscopy provides direct visualization and allows for resection of visible tumors, whereas biomarkers have variable sensitivity and specificity with the potential for false positives. Urinary biomarkers are being incorporated as adjuncts to traditional surveillance, however, as they offer minimal discomfort and invasiveness for patients. Ongoing research is exploring novel biomarker panels and genomic assays to better personalize surveillance regimens and reduce the burden of routine cystoscopy without compromising oncologic safety. Learn more about long-term monitoring for bladder cancer. Neoadjuvant cisplatin-based chemotherapy, typically gemcitabine plus cisplatin (GC) or methotrexate-vinblastine-doxorubicin-cisplatin (MVAC), has been shown to improve overall survival, with some studies finding a 10% benefit in 5-year survival. As a result, neoadjuvant chemotherapy is considered a standard of care for eligible patients with muscle-invasive bladder cancer. For cisplatin-ineligible patients, ongoing trials are evaluating alternative treatment options in the neoadjuvant setting. Molecular subtyping, while there is not yet currently sufficient evidence to be the standard of care, may help to inform treatment decision-making and offer the potential for more targeted therapies. Learn more about neoadjuvant therapy for bladder cancer.
Yahoo
30-06-2025
- Business
- Yahoo
I-Mab Highlights Positive Givastomig Phase 1b Dose Escalation Data in Combination with Immunochemotherapy in Patients with 1L Gastric Cancers at ESMO GI 2025
71% objective response rate (ORR) (12/17) per RECIST v1.1, with a favorable safety profile 83% ORR (10/12) in patients across doses selected for ongoing dose expansion study Responses observed in patients with low PD-L1 and/or CLDN18.2 expression Updated results to be presented at ESMO GI on July 2nd Company to host investor event on July 8th ROCKVILLE, Md., June 26, 2025 (GLOBE NEWSWIRE) -- I-Mab (NASDAQ: IMAB) (the 'Company'), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, today announced publication of ESMO Gastrointestinal Cancers Congress 2025 (ESMO GI 2025) abstract #388MO related to positive data from a Phase 1b study evaluating givastomig in combination with nivolumab and mFOLFOX6 chemotherapy for metastatic gastric cancers. An objective response rate (ORR) of 71% (12/17) was observed across all dose levels with an ORR of 83% (10/12) observed at dose levels selected for the ongoing dose expansion study (8 and 12 mg/kg). Responses were rapid and deepened over time, and were observed in tumors with low levels of PD-L1 expression and/or low levels of Claudin 18.2 (CLDN18.2) expression. There was a favorable safety profile, with low incidence of GI and liver toxicities. I-Mab intends to host a virtual investor event on Tuesday, July 8th (register here) to recap the data being presented at ESMO GI. The abstract is based on the results of the dose escalation part of a Phase 1b study (NCT04900818) evaluating the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of givastomig used in combination with nivolumab and mFOLFOX6 as first line therapy (1L) in patients with Claudin 18.2-positive gastric cancers (≥1+ intensity in ≥1% of cells). The primary endpoint is safety. The study only enrolled patients in the U.S. 'We are excited to share positive initial data from the Phase 1b dose escalation study of givastomig in gastric cancers at ESMO GI 2025. Givastomig shows promising activity in the first line setting, with responses that are both rapid onset and durable, deepening over time. This is the first study to evaluate givastomig in combination with immunochemotherapy and we are very pleased by the overall tolerability, consistent pharmacokinetic data and soluble 4-1BB induction. We look forward to sharing the data with the oncology and investment communities at ESMO GI 2025 on July 2nd,' said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab. 'Givastomig's strong response data and favorable safety profile are encouraging. I look forward to presenting the data for this novel Claudin 18.2 targeted therapy next week at ESMO GI and discussing with colleagues,' said Samuel J Klempner, MD, Associate Professor of Medicine at Massachusetts General Hospital. 'Gastroesophageal cancers continue to be a significant unmet medical need, and novel combination approaches are critical. On behalf of the study team, I am enthusiastic to continue to support the givastomig clinical program.' ESMO GI Presentation Details: Title: Preliminary Safety and Efficacy of Givastomig, a Novel Claudin 18.2/4-1BB Bispecific Antibody, in Combination with Nivolumab and mFOLFOX in Metastatic Gastroesophageal Carcinoma (mGEC)Speaker: Samuel J. Klempner, MD, Associate Professor of Medicine, Massachusetts General HospitalPresentation Number: 388MODate and Time: Wednesday, July 2nd at 16:50 CEST (10:50am EST) Givastomig Phase 1b Dose Escalation Data Summary in 1L Gastric Cancers 17 advanced metastatic gastric cancer patients were treated with givastomig across the 5 mg/kg (n=5), 8 mg/kg (n=6), and 12 mg/kg (n=6) dose levels as of the February 28, 2025, data cutoff. All patients were efficacy evaluable Patient Characteristics: The 17 patients enrolled in the study were treatment naïve metastatic gastric, esophageal or gastroesophageal adenocarcinomas Patients were HER2-negative, Claudin 18.2-positive (defined as >1+ intensity in >1% of tumor cells) regardless of PD-L1 expression levels All patients were enrolled at sites within the United States Efficacy Results: Objective Response Rates (ORRs): 71% of patients (12/17) achieved a partial response (PR) per RECIST v1.1 5 mg/kg (2/5) 8 mg/kg (5/6) 12 mg/kg (5/6), with one unconfirmed response as of the data cutoff At the doses selected for dose expansion (8 and 12 mg/kg), 83% (10/12) of patients achieved PRs 80% of patients (4/5) with CLDN18.2 expression below 75% (CLDN-Low) achieved a PR. The CLDN-Low response rate increased to 100% of patients (3/3) in the doses selected for expansion (8 and 12 mg/kg) The disease control rate (DCR) was 100% across the three dose levels Dose-dependent PK was observed, similar to monotherapy PK. Patients also experienced a dose dependent induction of soluble 4-1BB, a positive indicator of T cell activation and engagement ORR: % (n) All(n=17) Cohorts Chosen for expansion(8 and 12 mg/kg)(n=12) PD-L1 Any 71 (12/17) 83 (10/12) ≥5 82 (9/11) 89 (8/9) <5 50 (3/6) 67 (2/3) ≥1 73 (11/15) 82 (9/11) <1 50 (1/2) 100 (1/1) CLDN18.2 ≥75 67 (8/12) 78 (7/9) <75 80 (4/5) 100 (3/3) Durability: 8 of 17 patients remained on study treatment and the longest treatment duration was 11.3 months as of the data cutoff Safety: No dose limiting toxicities (DLT) were observed and a maximum tolerated dose (MTD) was not reached Common treatment related adverse events (TRAEs, ≥10% of patients) were generally Grade 1 or Grade 2 including nausea, vomiting, infusion related reaction, fatigue, decreased appetite, diarrhea, abdominal pain, chills, dyspepsia and gastritis Grade 3 TRAEs attributed to givastomig were rare, with single cases of abdominal pain, ALT/AST increases, gastritis, and infusion related reaction No Grade 4 or Grade 5 TRAEs were reported Virtual Investor Event: Register for the Post-ESMO GI 2025 Investor Event here. A replay of the webinar will be accessible on the News & Events page of the I-Mab website for 90 days. About Givastomig Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further potential in other solid tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents. An ongoing Phase 1b study is evaluating givastomig for the treatment of gastric cancer in the 1L setting in combination with standard of care, nivolumab (an anti-PD-1 checkpoint inhibitor) plus chemotherapy, in dose escalation and dose expansion cohorts. Dose escalation is complete, and enrollment in the first dose expansion cohort (n=20) finished ahead of schedule. Enrollment continues to progress ahead of schedule in the second dose expansion cohort (n=20). The study builds on positive Phase 1 monotherapy data. Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio. About I-Mab I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer. The Company's differentiated pipeline is led by givastomig, a potential best-in-class, bispecific antibody (Claudin 18.2 x 4-1BB) designed to treat Claudin 18.2-positive gastric cancers. Givastomig conditionally activates T cells via the 4-1BB signaling pathway in the tumor microenvironment where Claudin 18.2 is expressed. Givastomig is being developed for first-line metastatic gastric cancers, with additional potential in other solid tumors. In Phase 1 trials, givastomig was observed to maintain strong tumor-binding and anti-tumor activity, attributable to a potential synergistic effect of proximal interaction with Claudin 18.2 and 4-1BB, while minimizing toxicities commonly seen with other 4-1BB agents. For more information, please visit and follow us on LinkedIn and X. I-Mab Forward-Looking Statements This announcement contains forward-looking statements. These statements are made under the 'safe harbor' provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as 'will', 'expects', 'believes', 'designed to', 'anticipates', 'future', 'intends', 'plans', 'potential', 'estimates', 'confident', and similar terms or the negative thereof. I-Mab may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the SEC), in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about I-Mab's beliefs and expectations, are forward-looking statements. Forward-looking statements in this press release include, without limitation, statements regarding: the Company's pipeline and clinical development of I-Mab's drug candidates, including givastomig; the projected advancement of the Company's portfolio and anticipated milestones and related timing; the Company's expectations regarding the impact of data from ongoing and future clinical trials; the timing and progress of studies and trials (including with respect to patient enrollment); the potential benefits of givastomig; and the availability of data and information from ongoing studies and trials. Forward-looking statements involve inherent risks and uncertainties that may cause actual results to differ materially from those contained in these forward-looking statements, including but not limited to the following: I-Mab's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may or may not support further development or New Drug Application/Biologics License Application (NDA/BLA) approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab's drug candidates; I-Mab's ability to achieve commercial success for its drug candidates, if approved; I-Mab's ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab's reliance on third parties to conduct drug development, manufacturing and other services; and I-Mab's limited operating history and I-Mab's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the 'Risk Factors' section in I-Mab's annual report on Form 20-F filed with the SEC on April 3, 2025, as well as the discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the SEC. All forward-looking statements are based on information currently available to I-Mab. I-Mab undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. I-Mab Investor & Media Contacts PJ Kelleher LifeSci Advisors +1-617-430-7579 pkelleher@ IR@ Error 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
13-06-2025
- Health
- Medscape
Nivolumab Plus Chemotherapy Improves Survival in Lung Cancer
Adding nivolumab to neoadjuvant chemotherapy significantly improved 5-year overall survival among patients with resectable non-small cell lung cancer (NSCLC), according to findings from a phase 3 trial presented at the recent American Society of Clinical Oncology (ASCO) 2025 annual meeting. The survival benefit was more pronounced in patients who achieved a pathologic complete response or a presurgery clearance of circulating tumor DNA (ctDNA). METHODOLOGY: The phase 3 CheckMate 816 trial has shown that compared with neoadjuvant chemotherapy alone, nivolumab plus chemotherapy improvespathologic complete response rates and event-free survival in patients with stage IB-IIIA resectable NSCLC. Based on these findings, this regimen was approved for this patient population in the US, EU, and other places. compared with neoadjuvant chemotherapy alone, nivolumab plus chemotherapy improvespathologic complete response rates and event-free survival in patients with stage IB-IIIA resectable NSCLC. Based on these findings, this regimen was approved for this patient population in the US, EU, and other places. Researchers are now reporting the final, prespecified analysis of overall survival. In the trial, 358 patients with stage IB-IIIA resectable NSCLC were randomly assigned to receive either nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone every 3 weeks for three cycles. Surgery was performed within 6 weeks of completing neoadjuvant treatment. Postoperative adjuvant chemotherapy, radiotherapy, or both were permitted. Primary endpoints were event-free survival and pathologic complete response. Overall survival was the key secondary endpoint. The median follow-up duration was 68.4 months. TAKEAWAY: The 5-year overall survival rate was 65.4% with nivolumab plus chemotherapy vs 55.0% with chemotherapy alone. Nivolumab plus chemotherapy reduced the risk for death by 28% (hazard ratio [HR], 0.72; P = .048). = .048). Among patients who received the combination therapy, the 5-year overall survival rate was 95.3% for those who achieved a pathological complete response vs 55.7% for those who did not. Overall, 24% of patients in the nivolumab group achieved a pathological complete response vs only 2.2% in the chemotherapy group. ctDNA clearance before surgery was a strong prognostic indicator, regardless of treatment. At 5 years, overall survival was 75.0% among patients with ctDNA clearance vs 52.6% in those without (HR for death, 0.38 in the nivolumab group and 0.39 in the chemotherapy-only group). The combination therapy was associated with consistent survival benefits across disease stage and PDL-1 expression levels. The 5-year lung cancer-specific survival rate was 74.9% with nivolumab plus chemotherapy vs 65.1% with chemotherapy alone (HR, 0.65). No new safety concerns emerged, and there were no new deaths related to a trial treatment. IN PRACTICE: 'In this trial, we found that the use of neoadjuvant nivolumab plus chemotherapy resulted in significantly longer overall survival than chemotherapy alone, along with long-term benefit regarding event-free survival,' the authors wrote. 'These findings support the hypothesis that neoadjuvant chemoimmunotherapy can have a profound impact on the course of a patient's life when paired with the curative potential of surgical resection.' SOURCE: This study, led by Patrick M. Forde, MB, BCh, PhD, Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland, was published online in The New England Journal of Medicine and presented at ASCO. LIMITATIONS: Although the overall survival with nivolumab plus chemotherapy achieved statistical significance, the margin was narrow. Additionally, several subgroups in the exploratory analyses were too small for adequate statistical comparison, requiring cautious interpretation of these results. Black patients were underrepresented, which may have affected the generalizability of the findings. DISCLOSURES: This study was funded by Bristol Myers Squibb. Five authors declared being employees of Bristol Myers Squibb, with some holding stock or stock options with the company. Several authors declared working as consultants or having other ties with various sources including Bristol Myers Squibb.
