IMGN151 for Ovarian Cancer
Recruiting in Palo Alto (17 mi)
+24 other locations
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: AbbVie
Disqualifiers: Ocular disorders, Cardiac disease, Stroke, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing IMGN151, a new drug, in adults with certain recurrent cancers to see if it is safe, how the body handles it, if it causes immune reactions, and if it can help fight the cancer.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
What data supports the effectiveness of the drug IMGN151 for ovarian cancer?
The drug mirvetuximab soravtansine, which is similar to IMGN151, showed promising results in treating platinum-resistant ovarian cancer, with a 26% response rate and manageable side effects. This suggests that IMGN151, which may have similar properties, could also be effective.
12345What makes the drug IMGN151 unique for treating ovarian cancer?
IMGN151 is unique because it is an antibody-drug conjugate, which means it combines an antibody with a chemotherapy drug to specifically target and kill cancer cells, potentially reducing side effects compared to traditional chemotherapy.
678910Eligibility Criteria
Adults with recurrent endometrial, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers can join this trial. They must have had prior therapy and be in good health with proper organ function. Those who are pregnant, breastfeeding, or have certain other medical conditions like uncontrolled hypertension or recent strokes cannot participate.Inclusion Criteria
I am willing to provide a sample of my tumor for testing.
I am 18 years old or older.
Patients must have completed prior therapy within specified times
+10 more
Exclusion Criteria
I do not have any serious illnesses or active infections.
I have had cancer other than my current one in the last 3 years.
Prior known hypersensitivity reactions to study drugs and/or any of their excipients
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose-Escalation and Expansion
Participants receive IMGN151 via intravenous infusion on Day 1 of each 3-week cycle to determine safety, tolerability, and preliminary antitumor activity
Up to 3 years
Every 3 weeks (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 1 year
Participant Groups
The study is testing IMGN151's safety and effectiveness for patients with specific recurrent cancers. It's a first-in-human study where the dosage will be increased gradually to find the optimal safe amount before expanding to more participants.
1Treatment groups
Experimental Treatment
Group I: IMGN151Experimental Treatment1 Intervention
IMGN151 is administered via intravenous (IV) infusion on Day 1 of Cycle 1 every 3-week cycle (Q3W).
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Karmanos Cancer InstituteDetroit, MI
City of HopeIrvine, CA
Roswell Park Comprehensive Cancer CenterBuffalo, NY
City of Hope National Medical Center /ID# 269036Duarte, CA
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
ImmunoGen, Inc.Lead Sponsor
References
Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study. [2019]Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.
Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer. [2022]Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show that LRRC15, a type-I 15-leucine-rich repeat-containing membrane protein, highly overexpressed in ovarian cancer bowel metastases compared with matched primary tumors and acts as a potent promoter of omental metastasis. Complementary models of ovarian cancer demonstrated that LRRC15 expression leads to inhibition of anoikis-induced cell death and promotes adhesion and invasion through matrices that mimic omentum. Mechanistically, LRRC15 interacted with β1-integrin to stimulate activation of focal adhesion kinase (FAK) signaling. As a therapeutic proof of concept, targeting LRRC15 with the specific antibody-drug conjugate ABBV-085 in both early and late metastatic ovarian cancer cell line xenograft models prevented metastatic dissemination, and these results were corroborated in metastatic patient-derived ovarian cancer xenograft models. Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting ovarian cancer metastasis and suggest a novel and promising therapy to target ovarian cancer metastases.
A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer. [2019]Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-α, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. We focus on the favorable tolerability and encouraging signals of efficacy that have emerged, most notably in patients with platinum-resistant disease. Ongoing Phase III monotherapy and Phase Ib/II combination trials evaluating its activity in the setting of platinum resistance are emphasized, which will help define its role in the evolving landscape of ovarian cancer therapy.
Optimal first-line treatment in ovarian cancer. [2022]Treatment of ovarian cancer remains challenging despite the high complete response rate seen after maximal surgical debulking surgery and platinum-combination chemotherapy. as most patients will relapse and eventually succumb to ovarian cancer, new strategies are urgently required to improve survival. a platinum-taxane combination has been the cornerstone of treatment for >15 years. Better use of these drugs is being explored through scheduling studies, and dose-dense or intraperitoneal (IP) therapies. Further improvements in treatment will most likely come from the integration of optimal chemotherapy with one or more of the hundreds of molecular-targeted agents that could be active in ovarian cancer. The greatest experience has been with anti-angiogenic agents. Two large phase III trials in first-line ovarian cancer have demonstrated a positive effect of bevacizumab when administered concurrently with chemotherapy and then as a maintenance treatment. In this review, we discuss the existing treatments for ovarian cancer and highlight areas of recent progress.
Analysis of adverse events and quality of life in high-grade serous ovarian cancer patients with Olaparib maintenance therapy: A single-center study in China. [2023]Olaparib showed good efficacy and tolerability in the maintenance treatment of patients with initial therapy or high-grade serous recurrent ovarian cancer patients. This study aimed to analyze adverse events (AEs) of patients taking Olaparib and the quality of life (QoL) with Olaparib in 1 center of China. The study included 98 patients who received Olaparib and 210 patients without Olaparib from July 2018 to October 2021 for high-grade serous ovarian cancer in the Gynecology Oncology Department of Jiangsu Provincial Hospital. Information of clinicopathologic characteristics was collected from medical records. Then, we used the QLQ-C30 and Quality of Life Ovarian Cancer 28 Questionnaire (QLQ-OV28) to determine the QoL of 98 patients with and 210 patients without Olaparib. Among all 98 patients with Olaparib, 66 patients in first-line and 32 patients in more than second-line treatment. Regarding the best objective response with Olaparib maintenance in 78 patients with partial remission from most recent chemotherapy, 3 (3.84%) patients showed complete response (CR) and 6 (7.69%) showed as partial response (PR), whereas stable disease was observed in 42 patients (53.84%) and 27 patients (34.6%) showed as progression disease. AEs of Grade 3 and more were: anemia in 16 patients (16.32%), neutropenia in 20 patients (20.40%), thrombocytopenia in 4 patients (4.08%), and headache in 4 patients (4.08%). Dose reduction and drug discontinuation accounted for 73.40% and 20.40%, respectively. Olaparib as maintenance therapy increased QoL on all functioning domains and several symptom domains. Consistent with previous clinical trials, Olaparib maintenance therapy was proved safe and effective. Most patients may experience Grade 1 and 2 AEs. Olaparib maintenance therapy can increase QoL in several domains.
CD151-α3β1 integrin complexes suppress ovarian tumor growth by repressing slug-mediated EMT and canonical Wnt signaling. [2018]Human ovarian cancer is diagnosed in the late, metastatic stages but the underlying mechanisms remain poorly understood. We report a surprising functional link between CD151-α3β1 integrin complexes and the malignancy of serous-type ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in 90% of metastatic lesions, while it remains detectable in 58% of primary tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses show that knocking down CD151 or α3 integrin enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcriptional complexes. Together, our study demonstrates that CD151-α3β1 integrin complexes regulate ovarian tumor growth by repressing Slug-mediated EMT and Wnt signaling.
Growth differentiation factor 15 stimulates rapamycin-sensitive ovarian cancer cell growth and invasion. [2021]Identification of novel molecular markers and therapeutic targets may improve survival rates for patients with ovarian cancer. In the current study, immunohistochemical (IHC) analysis of two human ovarian tumor tissue arrays showed high staining for GDF15 in a majority of tissues. Exogenous stimulation of ovarian cancer cell lines with recombinant human GDF15 (rhGDF15) or stable over-expression of a GDF15 expression plasmid promoted anchorage-independent growth, increased invasion, and up-regulation of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF). MMP inhibition suppressed GDF15-mediated invasion. In addition, IHC analysis of human ovarian tumor tissue arrays indicated that GDF15 expression correlated significantly with high MMP2 and MMP9 expression. Exogenous and endogenous GDF15 over-expression stimulated phosphorylation of p38, Erk1/2, and Akt. Pharmacologic inhibition of p38, MEK, or PI3K suppressed GDF15-stimulated growth. Further, proliferation, growth, and invasion of GDF15 stable clones were blocked by rapamycin. IHC analysis demonstrated significant correlation between GDF15 expression and phosphorylation of mTOR. Finally, knockdown of endogenous GDF15 or neutralization of secreted GDF15 suppressed invasion and growth of a GDF15-over-expressing ovarian cancer cell line. These data indicate that GDF15 over-expression, which occurred in a majority of human ovarian cancers, promoted rapamycin-sensitive invasion and growth of ovarian cancer cells. Inhibition of mTOR may be an effective therapeutic strategy for ovarian cancers that over-express GDF15. Future studies should examine GDF15 as a novel molecular target for blocking ovarian cancer progression.
Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer. [2018]The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC.
Elevated OGN expression correlates with the EMT signature and poor prognosis in ovarian carcinoma. [2020]Ovarian carcinoma is the most deadly gynaecological disease, with poor prognosis and limited predictive biomarkers. Recent evidence has indicated controversial roles of OGN in human malignancies, but the pathologic significance of OGN in ovarian carcinoma has not yet been determined. Here, we investigated the expression of OGN in ovarian carcinoma and determined its association with patient prognosis. We found that OGN expression was up-regulated in serous papillary cystadenocarcinoma and endometrioid adenocarcinoma compared to non-tumor tissues, but not in clear-cell ovarian carcinoma. Kaplan-Meier analysis showed that OGN expression was an adverse prognostic factor for both the overall survival and the progression-free survival of ovarian carcinoma patients. Higher OGN levels were positively associated with the activation of EMT-related gene signatures. Histological analysis further confirmed that OGN positive ovarian carcinoma cells expressed vimentin and displayed morphology of mesenchymal identity. Collectively, our preliminary results indicate that elevated expression of OGN is associated with the EMT process and may serve as a potential biomarker for prognosis in ovarian carcinoma.
Molecular characterization of a new ovarian cancer cell line, YDOV-151, established from mucinous cystadenocarcinoma. [2021]Ovarian cancer is a leading cause of death among gynecological malignancies. Established cancer cell lines are useful tools for clinical and basic researches. We have therefore established a new human ovarian cancer cell line, YDOV-151, derived from the mucinous cystadenocarcinoma and characterized it by the microarray analyses. A mucinous origin of the YDOV-151 was evident from light microscopy, and its epithelial-like character was confirmed with electron microscopy. No pathogenic mutations were found in the BRCA1 and BRCA2 genes. The subcutaneous transplantation of YDOV-151 cells into nude mice successfully induced the tumor mass after 3 weeks. cDNA microarray analysis revealed 1,926 genes (> 2-fold differences, P 7-fold) in YDOV-151 and had an available antibody assay for further validation. In SYBR Green real-time PCR, the relative expression levels of RGC32 (651-fold), LAMP3 (1,930-fold), and SLCO4A1 (20,598-fold) were significantly higher in YDOV-151 than in HOSEs (P