2022-501606-35-01招募中4 期
2022-501606-35-00 – Randomized, multicenter, open-label, Phase 3 study of mirvetuximab soravtansine in combination with bevacizumab versus bevacizumab alone as maintenance therapy for patients with FRα-high recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancers who have not progressed after second-line platinum-based chemotherapy plus bevacizumab (GLORIOSA).
Immunogen Biopharma (Ireland) Limited, Immunogen Inc.85 个研究点 分布在 9 个国家目标入组 110 人开始时间: 2023年11月6日最近更新:
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 85
- 主要终点
- PFS, as assessed by BICR per RECIST v1.1, defined as the time from date of randomization until BICR-assessed PD or death due to any cause, whichever occurs first. PFS as assessed by the investigator, as a sensitivity analysis, in the same patient population
研究概览
简要总结
To compare progression-free survival (PFS), as assessed by a blinded independent central review (BICR) per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), in patients who have not progressed after platinum-based chemotherapy (doublet) plus bevacizumab and who are randomized to maintenance mirvetuximab soravtansine (MIRV) plus bevacizumab (Arm 1) or bevacizumab alone (Arm 2) -PFS will also be assessed, as a sensitivity analysis, by the investigator in the same patient population
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Patients must be ≥ 18 years of age and ≥ age of majority
- •Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.10.7) while on study medication during the study and for at least 7 months after the last dose of MIRV and 6 months after the last dose of bevacizumab.
- •FCBP must have a negative pregnancy test within 4 days before the first dose of therapy.
- •Patients must have an Eastern Cooperative Oncology Group performance status of 0 or
- •Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
- •Patients must be willing to provide documentation of a positive high tumor FRα expression. This may be obtained either via results from the regulatory agency-approved Ventana FOLR1 (FOLR1-2.1) Assay or via tissue testing by the study tissue testing laboratory. Patients undergoing pre-screening must provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of high FRα expression (reported as “positive”) as defined by the Ventana FOLR1 (FOLR1-2.1) Assay in a tissue testing laboratory. Patients must be confirmed FRα-high as defined by FRα positivity of ≥ 75% of tumor membrane staining at ≥ 2+ intensity (PS2+) for entry into the study. Note: Samples may be submitted for central testing as soon as patients pass the 6-month time point for platinum sensitivity (ie, sites do not have to wait for recurrence to determine FRα expression status).
- •Where available as standard of care, prior testing on the tumor or prior germline testing of both BRCA1 and BRCA2 is required for eligibility. If not done prior, tumor or germline testing will need to be done before study entry. Somatic or germline BRCA-positive patients must have received prior treatment with a PARPi in maintenance following first-line treatment unless documented as clinically contraindicated. Note: Local tumor or germline BRCA testing will be acceptable for stratification. If the patient has not been tested, recommend archival tumor samples to be assessed for tissue BRCA. Prior PARPi and/or bevacizumab use during first line maintenance therapy is allowed but not required.
- •Patients’ disease must have relapsed after frontline (first line) platinum-based chemotherapy and must be platinum-sensitive defined as progression greater than 6 months from last dose of primary platinum therapy. Note: Bevacizumab treatment is allowed, but not required, in frontline regimen. HIPEC is allowed in frontline regimen.
- •Patients must be appropriate for platinum-based triplet therapy for treatment of their first recurrence of PSOC (entering at Run-In phase) or undergoing or have completed triplet therapy for treatment of their first recurrence of PSOC (entering at maintenance phase).
- •Patients must have received no less than 4 and no greater than 8 cycles of platinum-based triplet therapy in the second line, to include no less than 3 cycles of bevacizumab in combination with platinum-based chemotherapy. If the number of cycles received is less than 6 due to toxicity, this must be documented and toxicity assessed as unlikely related to bevacizumab. Note: A minimum of 4 cycles of combination chemotherapy is required. If carboplatin (or cisplatin), paclitaxel, gemcitabine, or pegylated liposomal doxorubicin (PLD) is stopped due to toxicity, up to 4 additional cycles of single agent in combination with bevacizumab is acceptable if appropriately documented.
- •In the case of interval secondary cytoreductive surgery, patients are permitted to have received only 2 cycles of bevacizumab if given in combination with the last 3 cycles of platinum-based triplet therapy in the second line. In the case of cytoreductive surgery before second-line platinum-based triplet therapy, patients must have received no fewer than 3 cycles of bevacizumab in combination with platinum-based chemotherapy after their surgery and before randomization.
- •Patients either will receive (per investigator’s choice), must be receiving, or have received paclitaxel, gemcitabine, or pegylated liposomal doxorubicin as the partner drug to platinum-based triplet therapy in the second line.
- •The following requirements are for patients who are HIV positive: a. On established highly active antiretroviral therapy (HAART) for ≥ 12 weeks with an HIV viral load of less than 200 copies/mL; HAART is a requirement for the duration of the study. The specific agents are at the discretion of the investigator but should be checked for interaction with study agents before enrollment; b. Cluster of differentiation 4 (CD4+) T cell counts ≥ 350 cell/μL; c. No AIDS-defining opportunistic infection within the past 12 months; d. No history of other AIDS-defining illness besides opportunistic infection > 12 months ago Note: Use of experimental antiretroviral agents are not allowed, HIV-positive patients must be managed in conjunction with an HIV specialist and managed according to the current local guidelines for the prevention of opportunistic infections in HIV infected adults. Note: HIV testing is not required for study enrollment in patients not known to be HIV positive
- •The response to triplet therapy must be a CR, PR, or SD, per the investigator, in the second line to be eligible for randomization. All patients will have CT/MRI scans and CA 125 measurements at least 3 weeks but no more than 8 weeks after their last planned dose of triplet therapy and before randomization.
- •Patients must receive the first dose of maintenance therapy no later than 10 weeks from the last dose of platinum-based triplet therapy in the second line (defined as Day 1 of last cycle of platinum-based triplet therapy in second line).
- •After completion of triplet therapy and before randomization, patients must meet one of the following criteria: a. Have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator), and determined by the investigator to have either SD,PR or CR to their treatment; or b. Have persistently elevated CA-125 without measurable disease and determined by the investigator to have either SD or a PR to their treatment; or c. Have clinically no evidence of disease by both radiographic interpretation by the investigator and normalization of their CA-125, determined to be a CR.
- •Patients must have stabilized or recovered (to Grade 1 or baseline) from all prior therapyrelated toxicities (excluding alopecia).
- •Patients must have completed any major surgery at least 4 weeks before the first dose of study treatment (either Run-In or maintenance therapy) and have recovered or stabilized from the side effects of prior surgery before the first dose of treatment on study.Targeted radiation is allowed with a washout period of 2 weeks.
- •Patients must have adequate hematologic, liver, and kidney functions at the time of randomization and before first dose defined as follows: a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 10 days of C1D1 of maintenance treatment b. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the prior 10 days of C1D1 of maintenance treatment c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 10 days of C1D1 of maintenance treatment.Note: Patients with Grade 2 anemia are permitted to enroll. d. Serum creatinine ≤ 1.5 × upper limit of normal (ULN) e. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 × ULN f. Serum bilirubin ≤ 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN) g. Serum albumin ≥ 2 g/dL. Note: For any patients who have received a transfusion to correct a laboratory abnormality during the timeframe defined above, they should have repeat laboratory assessments to confirm that they meet the criteria no sooner than 4 days prior to dosing.
- •Patients or their legally authorized representative(s) must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements and are able to complete the scheduled assessments. Note: If ICF is signed by a legally authorized representative, certain study assessments, including ocular symptom assessments, adverse event (AE) reporting, and patient-reported outcome (PRO), must be completed by the patient.
排除标准
- •Patients with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade/borderline ovarian tumor
- •Patients with clinically significant cardiac disease including, but not limited to, any of the following: a. Myocardial infarction ≤ 6 months prior to C1D1 of maintenance treatment b. Unstable angina pectoris c. Uncontrolled congestive heart failure (New York Heart Association > class II) d. Uncontrolled ≥ Grade 3 hypertension (per CTCAE) e. Uncontrolled cardiac arrhythmias
- •Patients with a history of hemorrhagic or ischemic stroke within 6 months before enrollment
- •Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
- •Patients with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings)
- •History of bowel obstruction (including sub-occlusive disease) related to underlying disease within 6 months before the start of maintenance study treatment (triplet therapy for Run-In patients)
- •History of abdominal fistula or gastrointestinal perforation
- •Intra-abdominal abscess, evidence of rectosigmoid involvement by pelvic examination, bowel involvement on CT scan, or clinical symptoms of bowel obstruction within 4 weeks prior to randomization (or within 4 weeks prior to starting triplet therapy for Run- In patients)
- •Clinically significant proteinuria: urine-protein to creatinine (UPC) ratio ≥ 1.0 or urine dipstick result ≥ 2+; patients with UPC ratio ≥ 1.0 or ≥ 2+ proteinuria should undergo 24- hour urine collection and must show result ≤ 2 g of protein in a 24-hour period
- •History of Grade 4 thromboembolic events
- •Patients not appropriate for bevacizumab 15 mg/kg dosing at the start of maintenance therapy as per the treating physician
- •More than one line of prior chemotherapy before current/planned triplet therapy. Lines of prior anticancer therapy are counted with the following considerations: a. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens. b. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently). c. Change due to toxicity will be considered part of the proceeding line of therapy.d.Use of hormonal therapy in the first-line therapy setting of a CA-125 elevation without evidence of disease on imaging is allowed and will not be counted as a line of therapy for recurrent disease.
- •Patients requiring use of folate-containing supplements (eg, folate deficiency)
- •Patients with prior hypersensitivity to monoclonal antibodies (mAbs)
- •Women who are pregnant or breastfeeding
- •Patients who received prior treatment with MIRV or other FRα-targeting agents
- •Patients with untreated or symptomatic central nervous system metastases
- •Patients with a history of other malignancy within 3 years prior to signing study consent Note: Patients with tumors with a negligible risk for metastasis or death (eg, controlled basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.
- •Prior known hypersensitivity reactions to study drugs or any of their excipients
- •Patients with PD while on or following platinum-based triplet therapy
- •After completion of triplet therapy and prior to randomization: Patients who receive an intervening dose of bevacizumab after completing the planned second-line triplet therapy (before randomization). (Note: The Day 15 dose of bevacizumab in the last prior cycle of triplet therapy including pegylated liposomal doxorubicin is not considered as an intervening dose).
- •Patients with prior whole-pelvic or other wide-field radiotherapy affecting at least 20% of the bone marrow.Note: For patients entering on Run-In, exclusion criterion 5 must be satisfied at time of enrollment. All criteria will need to be met prior to randomization.
- •Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE).
- •Patients with the following ocular history and/or concurrent disorders: b.Active or chronic corneal epithelial disorders other than non-confluent superficial keratopathy/keratitis, including confluent superficial punctate keratopathy/keratitis (SPK) not expected to resolve to non-confluence or better within the screening window with standard-of-care intervention c. History of corneal transplantation d.Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery e.Active or chronic clinically significant (≥ Grade 3) corneal disorders (eg, Fuch’s dystrophy or neurotrophic keratitis) f.Active ocular conditions requiring ongoing treatment/monitoring, such as glaucoma, which is not adequately controlled with medication or surgery, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema or an ocular condition with high risk of retinal detachment g.Monocular vision with visual acuity in the worse-seeing eye worse than 20/200 or visual fields less than 20 degrees.
- •Patients with serious concurrent illness or clinically relevant active infection, including but not limited to, the following:a.Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection Patients with HBV positivity must not meet criteria for anti-HBV therapy and must be HBsAg-negative. Patients with HCV positivity must have completed curative antiviral treatment and have either a negative HCV RNA or an undetectable viral load. b. HIV infection (if inclusion criterion #20 is not met).c.Active cytomegalovirus infection. d.Any other concurrent infectious disease requiring intravenous (IV) antibiotics within 2 weeks before the first dose of maintenance therapy. Note: Testing at screening is not required for the above infections unless clinically indicated.
- •Patients with a history of multiple sclerosis or other demyelinating diseases and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
结局指标
主要结局
PFS, as assessed by BICR per RECIST v1.1, defined as the time from date of randomization until BICR-assessed PD or death due to any cause, whichever occurs first. PFS as assessed by the investigator, as a sensitivity analysis, in the same patient population
PFS, as assessed by BICR per RECIST v1.1, defined as the time from date of randomization until BICR-assessed PD or death due to any cause, whichever occurs first. PFS as assessed by the investigator, as a sensitivity analysis, in the same patient population
次要结局
- CA-125 response rate per GCIG criteria
- HRQoL/PRO measured by NFOSI-18 DRS-P
- OS defined as the time from randomization to death due to any cause. Patients alive at the time of analysis will be censored at the last date known to be alive.
- Treatment-emergent adverse events (TEAEs) and laboratory test results, physical examination (PE) findings, and vital signs
- PFS2 as assessed by the investigator, defined as the time from date of randomization until second disease progression or death due to any cause, whichever occurs first
- ORR as assessed by the investigator and by BICR in patients who have measurable disease per RECIST v1.1 at randomization
- DOR as assessed by the investigator and by BICR in patients who have measurable disease per RECIST v1.1 at randomization and achieved a confirmed response of CR or PR after maintenance therapy
- DFS as assessed by the investigator and by BICR in patients who have no measurable disease per RECIST v1.1 at randomization
研究者
Global Clinical Trials Helpdesk
Scientific
Immunogen Inc.
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