Latest news with #ovarianCancer
Medscape
2 days ago
- Health
- Medscape
Fact or Fiction: Ovarian Cancer and Drug Resistance
In ovarian cancer, the emergence of drug resistance has been shown to limit the durability of therapeutic treatment benefit and contribute substantially to ovarian cancer's high mortality rate. Factors such as treatment-free intervals and tumor microevolution may allow for re-sensitization to platinum agents in select patients. In addition to tumor biology, the tumor microenvironment plays a pivotal role in therapeutic resistance. Targeted therapies, once heralded as a solution to chemotherapy resistance, have been shown to face similar obstacles. Drug resistance in ovarian cancer management is an ongoing field of study as clinicians look to limit its impact improve outcomes. Platinum resistance in ovarian cancer is not always permanent. While many patients relapse with tumors less responsive to platinum-based chemotherapy, resistance can be dynamic. Mechanisms such as epigenetic alterations, modulation of DNA damage response, and temporary activation of drug efflux pumps may contribute to reversible resistance. Importantly, a subset of patients initially labeled as platinum-resistant may benefit from platinum rechallenge after a treatment-free interval, particularly if newer maintenance strategies or resensitizing agents are used. This has led to the concept of a "platinum-free interval" to help guide re-treatment. Understanding these nuances is crucial for tailoring treatment strategies and optimizing outcomes. Learn more about medications used in ovarian cancer. While HRD — often due to BRCA1/2 mutations — initially predicts strong sensitivity to DNA-damaging therapies like platinum agents and PARP inhibitors, resistance commonly emerges over time. A key mechanism is the restoration of homologous recombination through secondary or "reversion" mutations in HR pathway genes. These mutations enable tumor cells to resume high-fidelity DNA repair, diminishing the cytotoxic effects of therapy. Additionally, tumors may activate compensatory pathways such as non-homologous end joining or increase drug efflux activity. This resistance may not be detectable at diagnosis and can evolve under therapeutic pressure. Consequently, current research emphasizes longitudinal molecular monitoring to capture evolving resistance mechanisms. Clinically, this underscores the need for re-biopsy or circulating tumor DNA analysis to reassess HR status in recurrent disease, which may influence therapy selection. Learn more about the importance of biopsy in ovarian cancer. Tumor heterogeneity — both genetic and phenotypic — plays a central role in drug resistance and further complications treatment outcomes. Ovarian tumors often consist of diverse subclonal populations, some of which may possess innate resistance traits. Within a single ovarian tumor, multiple subclonal populations may coexist, each with distinct characteristics and sensitivity profiles. When systemic therapy is applied, sensitive clones are eliminated, but resistant ones may persist and expand. Single-cell and spatial transcriptomics studies have mapped how this clonal evolution occurs, revealing that treatment can select for resistant subpopulations not evident at baseline. Heterogeneity also affects the tumor microenvironment and immune response, further complicating therapeutic strategies. Clinically, this variability can manifest as mixed responses, where some lesions regress while others progress. Addressing heterogeneity remains a major challenge and has sparked interest in combination therapies and adaptive trial designs. Personalized treatment strategies based on real-time tumor profiling are likely to improve outcomes by accounting for this complexity. Learn more about ovarian cancer guidelines. Targeted therapies are susceptible to various resistance mechanisms, many of which overlap with those seen in chemotherapy. For example, resistance to PARP inhibitors, widely used in HRD-positive ovarian cancers, can arise from secondary mutations restoring DNA repair function or through enhanced drug efflux. Similarly, resistance to angiogenesis inhibitors may develop via upregulation of alternative pro-angiogenic pathways or changes in tumor vasculature that circumvent the need for VEGF signaling. Resistance is further complicated by factors such as epigenetic reprogramming and altered cell signaling networks. These findings have led to interest in combining targeted agents with immune checkpoint inhibitors, DNA repair modulators, or epigenetic therapies to overcome resistance. Future success with targeted therapy will likely depend on combination approaches informed by tumor genomics and adaptive resistance profiling. Learn more about risk assessment and genetic counseling in ovarian cancer. The tumor microenvironment (TME) is a key contributor to drug resistance in ovarian cancer. Immune cells such as regulatory T cells and tumor-associated macrophages (TAMs) create an immunosuppressive milieu that hinders effective therapy. Additionally, fibroblasts and extracellular matrix components can form physical barriers that limit drug penetration. Cytokines and growth factors secreted within the TME also modulate signaling pathways in tumor cells, promoting survival and resistance. Studies have shown that high TAM density is associated with poor response to both chemotherapy and immunotherapy, and interventions targeting the TME may help reverse resistance. This includes strategies like macrophage reprogramming, TME remodeling agents, and stromal-targeting therapies. Incorporating TME characteristics into clinical decision-making may help guide therapeutic combinations and predict response. Learn more about tumor biomarkers in ovarian cancer.
Medscape
3 days ago
- Business
- Medscape
Relacorilant + Nab-Paclitaxel Beneficial in Ovarian Cancer
Relacorilant, a selective glucocorticoid receptor antagonist, combined with nab-paclitaxel significantly improved progression-free survival in women with platinum-resistant ovarian cancer. The interim analysis also showed meaningful improvement in overall survival, with median survival extending from 11.50 to 15.97 months. METHODOLOGY: While platinum-based chemotherapy is initially effective, about 70% of patients experience disease relapse that becomes platinum-resistant. Relacorilant, a selective glucocorticoid receptor antagonist, has demonstrated synergy with paclitaxel in nonclinical tumor models. The combination with nab-paclitaxel was chosen for this study because it does not require corticosteroid coadministration. Researchers conducted a randomized, controlled, open-label, phase 3 trial (ROSELLA [GOG-3073/ENGOT-ov72]) at 117 hospitals and community oncology treatment centers across 14 countries in Australia, Europe, Latin America, North America, and South Korea. Participants included 381 patients aged 18 years or older with confirmed platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer; up to three previous lines of anticancer therapy; and measurable disease as per Response Evaluation Criteria in Solid Tumors (version 1.1). Analysis involved comparing relacorilant (150 mg orally the day before, of, and after nab-paclitaxel infusion) plus nab-paclitaxel (80 mg/m2 intravenously on days 1, 8, and 15 of each 28-day cycle) with nab-paclitaxel monotherapy (100 mg/m2 on the same schedule). TAKEAWAY: Patients receiving relacorilant plus nab-paclitaxel showed improved progression-free survival compared with those receiving nab-paclitaxel monotherapy (hazard ratio [HR], 0.70; 95% CI, 0.54-0.91; median, 6.54 months vs 5.52 months; stratified log-rank P = .0076). = .0076). Interim analysis revealed improved overall survival with relacorilant plus nab-paclitaxel vs nab-paclitaxel monotherapy (HR, 0.69; 95% CI, 0.52-0.92; median, 15.97 months vs 11.50 months; log-rank P = .0121). = .0121). Safety profiles were comparable between the groups when adjusted for nab-paclitaxel exposure, with no new safety signals observed. IN PRACTICE: 'Combined with the evidence from previous studies, our study supports relacorilant plus nab-paclitaxel as a potential new standard of care for patients with platinum-resistant ovarian cancer, without the need for biomarker selection. This study is the first positive clinical trial conducted with registrational intent for a selective glucocorticoid receptor antagonist in patients with cancer,' authors of the study wrote. SOURCE: Lead author Alexander B. Olawaiye, MD, of the University of Pittsburgh School of Medicine and UPMC Magee-Womens Hospital, both in Pittsburgh, presented the results of the study at American Society of Clinical Oncology (ASCO) 2025. A paper on the study was published online in The Lancet on June 2. LIMITATIONS: The open-label design and applicability to patients with more than three lines of anticancer therapy were noted as limitations. While the risk of bias in progression-free survival assessment was mitigated by using blinded independent central review and a dual primary endpoint of overall survival, the median duration of the follow-up for overall survival was less than the estimated median overall survival in the relacorilant combination group at interim analysis. DISCLOSURES: The study was funded by Corcept Therapeutics. The authors reported that adverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (version 5.0), with relatedness determined by the investigators. The funding source supported trial conduct, patient enrollment, and drug supply. The analysis, interpretation, writing, and submission decisions were the responsibility of the authors.
Associated Press
4 days ago
- Business
- Associated Press
OnCusp Therapeutics Announces Encouraging Initial Phase 1a Results from Ongoing First-in-Human Study Evaluating its CDH6-Directed Antibody-Drug Conjugate, CUSP06, in Platinum-Refractory/Resistant Ovarian Cancer and Other Advanced Solid Tumors at the 2025 ASCO Annual Meeting
CUSP06 is a CDH6-directed ADC with a differentiated profile and potentially best-in-class activity CUSP06 demonstrated a manageable safety profile, consistent with other TOP1-inhibitor ADCs Promising signs of efficacy were observed in patients with heavily pretreated platinum-resistant high-grade serous ovarian cancer (HGSOC) without CDH6 pre-selection PRINCETON, N.J., June 2, 2025 /PRNewswire/ -- OnCusp Therapeutics, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients, today announced initial Ph1a data from its ongoing Phase 1 open-label, multicenter dose escalation and expansion study evaluating CUSP06, a CDH6-directed antibody-drug conjugate (ADC) with a differentiated profile, in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. The data are being presented today at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting being held in Chicago, Illinois. 'We are excited by the early results, especially in platinum-resistant HGSOC, which demonstrated promising activity in a heavily pretreated population without requiring CDH6 biomarker selection,' said Dr. Bing Yuan, Co-Founder and CEO of OnCusp Therapeutics. 'These data, together with previously presented preclinical findings, underscore the best-in-class potential of CUSP06. We look forward to observing promising data in the Phase 1b study and to bringing this therapy to patients with ovarian cancer and other CDH6-expressing solid tumors.' The Phase 1 trial is an open-label, multicenter, first-in-human study of CUSP06. The primary objective of the study is to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of CUSP06 in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. The Phase 1a portion will determine the recommended doses for expansion and the Phase 1b portion will focus on further characterizing safety and efficacy in select tumor types. As of May 13, 2025, data are available for 37 patients who have received CUSP06 once every three weeks (Q3W) at doses ranging from 1.6 to 5.6 mg/kg. These patients were heavily pretreated, with a median of 4 prior lines of therapy. Promising efficacy was observed in patients with heavily pretreated platinum-resistant HGSOC without CDH6 pre-selection. The overall response rate (ORR) was 36% in HGSOC (9/25; 5 confirmed (including 2 responders who had previously received mirvetuximab treatment) and 4 unconfirmed partial responses (PRs)). All patients with unconfirmed PRs remain on treatment. The ORR reached 50% at both 4.0 mg/kg + prophylactic granulocyte colony-stimulating factor (G-CSF) and 4.4 mg/kg + G-CSF cohorts (3/6 and 1/2 patients, respectively); all responders remain on treatment. The clinical benefit rate (CBR) was 92% (23/25). CA-125 responses occurred in 45% of Gynecologic Cancer InterGroup (GCIG)-evaluable HGSOC patients, further supporting clinical activity. Responses were seen in low and high-CDH6-expressing tumors. CUSP06 has been well tolerated, with manageable hematologic toxicities as the most common treatment-related adverse events. These Phase 1a safety and efficacy results support continued evaluation of CUSP06 in platinum-resistant HGSOC and other CDH6-positive tumors in Phase 1b expansion cohorts. CUSP06 was recently granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of patients with platinum-resistant ovarian cancer. Poster Presentation Details: Title: First-in-human (FIH) Phase 1 study of CUSP06, a cadherin-6 (CDH6)-directed antibody-drug conjugate (ADC), in patients with platinum-refractory/resistant ovarian cancer and other advanced solid tumors. Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Date and Time: June 2 – 1:30 PM CDT Abstract Number: 3042 Poster Number: 357 Location: Hall A About CUSP06 CUSP06, a CDH6 ADC, is composed of a proprietary antibody with high CDH6 binding affinity, a protease-cleavable linker, and an exatecan payload (a potent and clinically validated topoisomerase-1 inhibitor). The linker is designed to complement the exatecan payload, enabling a stable and homogeneous ADC. The payload is a weak substrate for BCRP/P-gp, which are drug efflux pumps that drive chemoresistance to many therapies. In preclinical data, this linker-payload has been shown to have an increased 'bystander effect' compared with competitor ADCs. CUSP06 has a drug-to-antibody ratio of eight. OnCusp obtained the exclusive global rights (outside of China) to lead the development and commercialization of CUSP06 from Multitude Therapeutics in 2022. CUSP06 is being evaluated in a Phase 1 study in patients with platinum refractory/resistant ovarian cancer and other advanced solid tumors. Additional information on the CUSP06-1001 (NCT06234423) trial can be found at About OnCusp Therapeutics OnCusp Therapeutics, Inc., headquartered in Princeton, New Jersey, is a clinical-stage biopharmaceutical company dedicated to transforming cutting-edge preclinical innovation into clinically validated treatments for cancer patients. OnCusp was co-founded by Dr. Bing Yuan, Dr. Eric Slosberg, and Dr. Andy Fu, and has built a strong team of accomplished veterans with proven track records in building biotech startups, leading successful preclinical and clinical programs, and creating value through global partnerships. The company is committed to accelerating the advancement of globally competitive oncology assets for patients. OnCusp raised an oversubscribed $100 million Series A financing round in January 2024, co-led by Novo Holdings, OrbiMed, and F-Prime Capital. Contact: OnCusp Investors & Media: Argot Partners [email protected] View original content: SOURCE OnCusp Therapeutics
Yahoo
21-05-2025
- Politics
- Yahoo
Langhorne Manor small games of chance referendum may have fallen short: Unofficial results
One of the few towns in Bucks County with a ballot question was Langhorne Manor Borough, where voters appear to have upheld a prohibition on small games of chance. The initiative to allow small games of chance was led by Jay Ferraro, a former councilman and borough manager. Standing outside of borough hall, the town's sole polling place, on the day of the primary, he said he launched the effort on behalf of the Barbara T. Foundation, founded in memory of his late wife who died from ovarian cancer in 2023. 'It was one of her final requests,' Ferraro said. Bucks County election results: Check out our live vote returns If it had passed, the measure would limit games of chance to raffle baskets (such as baskets of cheer), pull tab games and 50-50 raffles. Ferraro said he hoped the games of chance revenue could be used toward finding a cure for ovarian cancer. He said he launched the ballot question after discovering they couldn't receive a county permit for games of chance until there was a referendum. He called the foundation a 'pure nonprofit' because everyone is a volunteer. 'We do not use one penny for overhead. Every dollar we raise goes right to research,' he said. Unofficial results from Bucks County, however, showed there were 101 votes against the proposal and just 74 in favor. This article originally appeared on Bucks County Courier Times: Voters say no to small games of chance referendum in Langhorne Manor
Yahoo
13-05-2025
- Business
- Yahoo
Imunon Inc (IMNN) Q1 2025 Earnings Call Highlights: Strategic Advances Amid Financial Challenges
Cash and Cash Equivalents: $2.9 million as of March 31, 2025. Research & Development Costs: $2.2 million for Q1 2025, down from $3.3 million in Q1 2024. General & Administrative Expenses: $2 million for Q1 2025, up from $1.7 million in Q1 2024. Net Loss: $4.1 million or $0.28 per share for Q1 2025, compared to $4.9 million or $0.52 per share in Q1 2024. Warning! GuruFocus has detected 3 Warning Signs with IMNN. Release Date: May 12, 2025 For the complete transcript of the earnings call, please refer to the full earnings call transcript. Imunon Inc (NASDAQ:IMNN) has initiated the first clinical site for their Phase 3 pivotal study of Imunon-001, targeting advanced ovarian cancer. The Phase 3 study, OVATION 3, is recognized by the medical community as a critical step towards delivering a new frontline treatment for women with limited options. Imunon-001's data has been accepted for an oral presentation at the ASCO Annual Meeting and for publication in the peer-reviewed journal Gynecologic Oncology. The company has a strategy to focus initially on a subgroup of HRD positive patients, which could lead to a faster and more cost-effective trial readout. Imunon Inc (NASDAQ:IMNN) is actively working on value-added financing and partnerships to secure a cash runway that supports their clinical timelines and strategic objectives. Imunon Inc (NASDAQ:IMNN) reported a net loss of $4.1 million for the first quarter of 2025, indicating ongoing financial challenges. The company had only $2.9 million in cash and cash equivalents as of March 31, 2025, highlighting the need for near-term financing. General & administrative expenses increased to $2 million in Q1 2025, up from $1.7 million in the same period in 2024, primarily due to higher employee-related expenses. The decrease in research & development costs from $3.3 million in Q1 2024 to $2.2 million in Q1 2025 may indicate reduced investment in certain areas. Imunon Inc (NASDAQ:IMNN) is facing dilution concerns as they consider options for raising capital to support their product development goals. Q: Can you provide details on the ASCO presentation and any new data analysis expected? A: Due to ASCO's embargo, we can't discuss the presentation's content in advance. However, we will share new information, which is central to being accepted for an oral presentation. We are excited for the presentation and Dr. Thaker's insights on the data. - Stacy Lindborg, CEO Q: How many sites are expected for the Phase 3 trial, and how is the statistical plan structured? A: We project about 45 sites. The analysis focuses on the HRD population first, where we expect the highest effect. There are two interim analyses and a final analysis based on HRD events. Overall survival is the primary endpoint for all populations. - Douglas Faller, Chief Medical Officer Q: What is the status of inventory and manufacturing capabilities for the OVATION 3 trial? A: We have brought the manufacturing of core active pharmaceutical ingredients in-house and are prepared for various enrollment plans. We have product ready and will continue to ensure availability. - Stacy Lindborg, CEO Q: What is the current status of the clinical trial with the Breakthrough Cancer Foundation, and are preliminary results expected this year? A: We have regular meetings with principal investigators and have initiated another site at the University of Oklahoma. Johns Hopkins is also preparing to screen patients. We expect to have data by the end of this year. - Douglas Faller, Chief Medical Officer Q: What are the near-term financial goals for Imunon? A: Our focus is on securing funds to strengthen our financial condition and advance the Phase 3 trial. We aim to cover OVATION 3 trial costs through corporate partnerships and equity financing, with updates expected by the end of the quarter. - Stacy Lindborg, CEO For the complete transcript of the earnings call, please refer to the full earnings call transcript. This article first appeared on GuruFocus.
