Clinical trial NCT06682988: A Study to Assess Adverse Events and Change in Disease Activity in Participants With Platinum-Resistant Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression Treated With Intravenously (IV) Infused Mirvetuximab Soravtansine
Official title: A Randomized Phase 2, Open-label Study of Mirvetuximab Soravtansine in Patients With Platinum-resistant Advanced High-grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-alpha Expression Testing 2 Schedules of Administration for Dose Optimization, With a Separate Cohort to Determine Starting Dose in Patients With Moderate Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced High-Grade Epithelial Ovarian
Primary Peritoneal
Fallopian Tube Cancers
High Folate Receptor-Alpha Expression
Platinum Resistant
Keywords: Advanced High-Grade Epithelial Ovarian
Primary Peritoneal
Fallopian Tube Cancers
High Folate Receptor-Alpha Expression
Platinum Resistant
Mirvetuximab Soravtansine
MIRV
IMGN853
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-11-12
Enrollment: 110
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess the safety and efficacy of for Mirvetuximab Soravtansine in participants with platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer (platinum-resistant ovarian cancer) (PROC) whose tumors express a high level of folate receptor alpha (FRα).

Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to cancer cells carrying a protein called folate receptor alpha (FRα). There are 2 cohorts in this study, the Randomized Phase 2 Cohort and the Hepatic Impairment Cohort. In the Randomized Phase 2 Cohort, participants are placed in 1 of 2 groups, called treatment arms. Each treatment arm receives MIRV on a different schedule (on day 1 every 21 days or on days 1 and 15 every 28 days). The Hepatic Impairment Cohort is designed to determine the starting dose of MIRV in patients with moderately abnormal liver function. Around 110 participants will be enrolled in the study at approximately 75 sites worldwide.

The total study duration will be approximately 24 months.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.


Eligibility criteria: Inclusion Criteria:

Both Cohorts

* Participants with a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
* Participants with platinum-resistant disease:

  * Participants with 1 prior line of platinum-based therapy who have received ≥ 4 cycles of platinum and had a response (complete response (CR) or partial response (PR)) followed by radiological progressive disease (PD) between \> 3 months and ≤ 6 months after the date of the last dose of platinum.
  * Participants with 2 or 3 prior lines of platinum-based therapy who had radiological PD

    * 6 months after the date of the last dose of platinum.
* Participants with progression diagnosed radiographically on or after their most recent line of therapy.
* Participants with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
* Participants with ≥ 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
* Participants with a tumor that is positive for folate receptor alpha (FRα) expression as determined by the Ventana folate receptor 1 (FOLR1) assay (≥ 75% of tumor staining at 2+ intensity).

Exclusion Criteria:

Both Cohorts

* Participants with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade or borderline ovarian tumor.
* Participants with primary platinum-refractory disease, defined as disease that did not respond (complete response (CR) or partial response (PR)) or that progressed radiographically within 3 months of the last dose of first-line platinum-containing chemotherapy.
* Participants with serious concurrent illness or clinically relevant active infection as outlined in the protocol
* Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to randomization.

Primary outcomes:
measure: Randomized Phase 2 Cohort: Percentage of Participants with Grade >= 2 Treatment-Emergent Corneal Adverse Events (AEs)
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Objective response rate (ORR)
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Maximal Concentration (Cmax) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Area Under the Plasma Concentration (AUC) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Trough Concentration (Ctrough) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Time to Maximal Concentration (Tmax) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Hepatic Impairment Cohort: Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
Secondary outcomes:
measure: Randomized Phase 2 Cohort: Percentage of Participants with Treatment-Emergent All-Grade Ocular AEs, Grade >= 2 Peripheral Neuropathy, All-Grade Infusion Reactions, and All-Grade Pneumonitis
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Progression-Free Survival (PFS)
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Overall Survival (OS)
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Maximal Concentration (Cmax) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Area Under the Plasma Concentration (AUC) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Trough Concentration (Ctrough) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Time to Maximal Observed Concentration (Tmax) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine
timeFrame: Up to Approximately 24 months
measure: Randomized Phase 2 Cohort: Change from baseline in two dosing methods while assessing drug response
timeFrame: Up to Approximately 24 months
measure: Both Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Approximately 24 months
measure: Both Cohorts: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator
timeFrame: Up to Approximately 24 months
measure: Both Cohorts: Percentage of Participants with Clinically Significant Laboratory Values (test) as Assessed by the Investigator
timeFrame: Up to Approximately 24 months
measure: Both Cohorts: Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings
timeFrame: Up to Approximately 24 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: First Physicians Group /ID# 272180
state: Florida
city: Edgewood
country: United States
facility: St. Elizabeth Medical Center - Edgewood /ID# 272113
state: Kentucky
city: Pittsburgh
country: United States
facility: Allegheny Health Network West Penn Hospital /ID# 272267
state: Pennsylvania
city: Chermside
country: Australia
facility: Icon Cancer Centre Chermside /ID# 272220
state: Queensland
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: