Breakthrough Clinical Results
Genmab announced it will present new data at the 2025 ASCO Annual Meeting, focusing on its late-stage oncology portfolio. Key highlights include the first disclosure of Phase 1/2 trial results for rinatabart sesutecan (Rina-S®) in recurrent/advanced endometrial cancer and long-term follow-up data from the Phase 1/2 EPCORE™ NHL-1 study of epcoritamab in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Genmab will also host a virtual investor update on the Rina-S data. Both Rina-S and epcoritamab are being investigated for various cancer indications, with ongoing Phase 3 trials for Rina-S in platinum-resistant ovarian cancer and multiple Phase 3 trials for epcoritamab across different lymphoma types.
Key Highlights
- First disclosure of Phase 1/2 rinatabart sesutecan (Rina-S®) data in recurrent/advanced endometrial cancer.
- Long-term follow-up data from the Phase 1/2 EPCORE™ NHL-1 study of epcoritamab in relapsed/refractory DLBCL.
- Genmab to host a virtual investor update on Rina-S data presented at ASCO.
- Ongoing Phase 3 trials for both Rina-S and epcoritamab in various cancer indications.
Incidence and Prevalence
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Emerging Mechanism of Action
Emerging Mechanisms of Action for Endometrial Cancer
Recent publications have revealed several key molecular mechanisms of action (MoA) that are emerging for endometrial cancer (EC) treatment and understanding:
Molecular Classification and Precision Medicine
Research has identified four molecular subtypes of EC through genome sequencing analyses. This molecular classification enables tailored adjuvant treatment by escalating or de-escalating therapy based on specific mutations, such as POLE-mutated and p53-mutated tumors. The expression of specific molecular signatures offers opportunities for novel targeted therapies.
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors have demonstrated significant benefit on prognosis in EC and are emerging as an important targeted therapy approach.
ARID1A as Prognostic Biomarker
ARID1A mutations have been identified in 33.3% of "no specific molecular subtype" (NSMP) EC cases. These mutations are associated with a higher risk of recurrence (37.5% vs 12.5%) and impaired progression-free survival (HR 3.96). ARID1A status could be used for further sub-classification and personalized treatment strategies.
Estrogen Pathway Modulation
Aromatase inhibitors show promise in EC therapy, especially in early-stage disease. These inhibitors interfere with estrogen biosynthesis by inhibiting aromatase activity and are particularly effective for Type I endometrial carcinoma (estrogen-dependent).
PI3K/AKT Pathway Alterations
PTEN loss of expression is found in 63.4% of tumors, more commonly in endometrioid adenocarcinoma (EEC). PIK3CA mutations are observed in 41.2% of cases, with a hot mutation spot at T544 in exon 9. p-AKT is positive in 59.2% of tumors, more frequently in EEC. Different PIK3CA mutations (exon 9 vs. exon 20) may have different prognostic impacts.
Epigenetic Regulators
Histone methyltransferase EZH2 and DNA methyltransferase DNMT3B are upregulated in EC. Both promote EC cell proliferation. EZH2 represses TCF3, a transcriptional activator of p21, while DNMT3B methylates the TCF3 promoter. Combined inhibition of EZH2 and DNMT3B with GSK126 and 5-Aza-2d showed synergistic anti-tumor effects.
KIFC1/HMGA1/c-myc Pathway
KIFC1 upregulation correlates with poor prognosis and promotes aerobic glycolysis by regulating the HMGA1/c-myc pathway. It affects expression of glycolytic genes (GLUT1, LDHA, HK2) and represents a potential target for EC diagnosis and therapy.
MicroRNA Regulation
MicroRNA-1271 (miR-1271) functions as a tumor suppressor in EC by targeting lactate dehydrogenase A (LDHA) and inhibiting cell proliferation and metastasis.
These emerging mechanisms provide new insights into EC pathogenesis and offer promising avenues for developing more effective and targeted therapeutic approaches.
Study Design Parameters
Study Design Parameters and Endpoints in Key Trials for Endometrial Cancer
Study Designs
Several key trials have been conducted to advance understanding and treatment of endometrial cancer (EC) with varied methodologies:
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A cross-sectional study of 318 women newly diagnosed with endometrial cancer conducted between December 2016-January 2020 at a reference center for gynecological cancer treatment, evaluating ultra-processed food consumption and its associations with clinical characteristics.
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Analysis of 72 endometrial cancer cases examining cyclooxygenase-2 (COX-2) expression and its correlation to various clinical parameters using immunohistochemical analysis.
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NRG oncology group summer symposium (2019) review focusing on uterine carcinosarcoma (UCS), combining expert presentations and literature search from MEDLINE and ClinicalTrials.gov.
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TCGA database study constructing a 9-related lncRNA prognostic model using Cox regression analysis of 1,731 ferroptosis-related long non-coding RNAs.
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Single-center retrospective analysis comparing pre-operative transvaginal ultrasound (TVUS) staging with final surgical stage in endometrial cancer patients treated between 2015-2019.
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Prospective phase II study of 50 patients with advanced or metastatic endometrial cancer treated with docetaxel 70 mg/m² intravenously on day 1 of a 3-week cycle.
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Retrospective multicenter study using data from three French centers between November 2010-December 2012, evaluating implementation of INCa guidelines.
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The North Central Cancer Treatment Group Phase III trial compared MVAC with AC for advanced endometrial cancer, with 28 patients randomly assigned to treatment regimens.
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ROGY Care trial (2011-2014): Longitudinal analysis of 215 endometrial cancer patients with questionnaires completed after initial treatment and follow-ups.
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Phase 2 study of sapanisertib: Investigated sapanisertib alone or in combination with paclitaxel or TAK-117 versus paclitaxel alone in four treatment arms.
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Phase II trial (NCT03367741): Combined immunotherapy (nivolumab) and antiangiogenic agent (cabozantinib) in recurrent endometrial cancer with 2:1 randomization.
Endpoints
The trials utilized various endpoints to measure efficacy and outcomes:
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Statistical significance was set at p<0.05 in the cross-sectional study of ultra-processed food consumption.
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The North Central Cancer Treatment Group Phase III trial measured complete response (CR), partial response (PR), progression-free survival (PFS), overall survival, and toxicity.
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ROGY Care trial assessed satisfaction with information provision and care, illness perceptions, anxiety, depression, and health-related quality of life.
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The Phase 2 sapanisertib study used progression-free survival (PFS) as the primary endpoint.
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Phase II trial of nivolumab and cabozantinib used RECIST-defined progression-free survival (PFS) as the primary endpoint, with immune analysis from baseline biopsies and serial peripheral blood mononuclear cell samples.
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The prospective phase II docetaxel trial in Egypt measured overall response rate, complete response, partial response, duration of response, time to progression, survival time, and toxicity.
The TCGA database study utilized Kaplan-Meier analysis, operating characteristic curves, decision curve analysis, Gene Set Enrichment Analysis, and evaluation of immune-infiltrating conditions.
Drug used in other indications
There is no information available in the provided context about rinatabart sesutecan clinical trials for any indications, including endometrial cancer or any other conditions. The context does not contain any data about intervention models for rinatabart sesutecan trials.