Mirvetuximab Soravtansine Monotherapy in Platinum-Sensitive Epithelial, Peritoneal, and Fallopian Tube Cancers (PICCOLO)

A Phase 2, Single Arm Study of Mirvetuximab Soravtansine in Recurrent Platinum-Sensitive, High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (PICCOLO)

PICCOLO (IMGN853-0419) is a Phase 2 multicenter, open label study designed to evaluate the safety and efficacy of Mirvetuximab Soravtansine in participants with platinum-sensitive ovarian, primary peritoneal or fallopian tube cancers with high folate receptor-alpha (FRα) expression.

Study Overview

• Status: Active, not recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer
• Intervention / Treatment: Drug: Mirvetuximab soravtansine

Detailed Description

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 the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRα). It is being developed for the treatment of subjects with recurrent platinum-sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Patients will have had at least 2 prior lines of therapy. These will include at least 2 lines of platinum-containing therapy or 1 line with a documented platinum allergy. FRα positivity will be defined by the Ventana FOLR1 (FOLR1- 2.1) CDx assay (Ventana FOLR1 Assay)

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Method, MD, MPH, MBA; Phone Number: 781-895-0600; Email: PICCOLOTrialDesk@ImmunoGen.com
• Study Contact Backup: Name: Noam Ponde, MD; Email: PICCOLOTrialDesk@ImmunoGen.com

Study Locations

• Australia
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Newcastle Private Hospital
    • St. Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • South Australia
    • Toorak Gardens, South Australia, Australia, 5065
      • Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
  • Victoria
    • Clayton, Victoria, Australia, 3165
      • Monash Health
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Subiaco Hospital
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Namur, Belgium, 5000
    • CHU UCL
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre - University Health Network
  • Quebec
    • Montréal, Quebec, Canada, H4A 3H1
      • McGill University Health Center
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Ciussse-Chus
• France
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13009
    • Institut Poali Calmette
  • Paris, France, 75020
    • Groupe Hospitalier Diaconesse, Croix Saint-Simon
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Plerin, France, 22190
    • Centre CARIO - HPCA
  • Saint-Herblain Cedex, France, 44805
    • ICO Centre Rene Gauducheau
  • Strasbourg, France, 67033
    • Institut de Cancerologie Strabsourg Europe Unité de recherche clinique
• Ireland
  • Cork, Ireland, 00
    • Bon Secours Hospital
  • Dublin, Ireland
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, D08 NHY1
    • St James's Hospital
  • Dublin, Ireland, D09 V2N0
    • Beaumont Hospital
  • Waterford, Ireland, X91 ER8E
    • University Hospital Waterford
• Italy
  • Bologna, Italy, 40138
    • Azienda Ospedaliero-Universitaria-IRCCS
  • Catania, Italy, 95126
    • Osperdale Cannizzaro di Catania
  • Milano, Italy, 20133
    • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Milano, Italy, 20141
    • IRCCS - Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Napoli
  • Ravenna, Italy, 48100
    • Azienda Unita Sanitaria Locale di Ravenna
  • Roma, Italy, 168
    • Fondazione Policlinico Universitario A. Gemelli IRCCS
• Spain
  • Badalona, Spain, 08916
    • Institut Català d'Oncologia - Hospital Universitari Germans Trias i Pujol, Unidad de Investigación Clínica, Servicio de Oncología, Institut Josep Carreres (IJC, 1ª planta)
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Barcelona, Spain, 8908
    • Institut Català d' Oncologia L' Hospitalet
  • Castelló, Spain, 12002
    • Complejo Hospitalario Provincial de Castellón
  • Cordoba, Spain, 14004
    • Hospital Reina Sofia
  • Jaen, Spain, 23007
    • Hospital Universitario HU de Jaen
  • Madrid, Spain
    • Hospital La Paz
  • Madrid, Spain, 28050
    • Hospital de San Chinarro-Clara Campal
  • Madrid, Spain, 28033
    • Hospital MD Anderson Cancer Center Madrid
  • Sevilla, Spain, 41013
    • Virgen del Rocío
  • Valencia, Spain
    • Hospital Clinico
  • Madrid
    • Pamplona, Madrid, Spain, 28027
      • ClÃ-nica Universidad de Navarra (CUN)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham - Division of Gynecology Oncology O'Neal Comprehensive Cancer Center
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care/Providence Alaska Medical Center
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC - HOPE
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • UCLA-JCCC Dept of OBGYN - Women's Health Clinical Research Unit
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8063
      • Yale University School Of Medicine
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - South
    • Miami, Florida, United States, 33136
      • University of Miami
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist North Division
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists - Panhandle
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialist East Division
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Women's Cancer Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Partners - Women's Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital-Moll Cancer Center
    • Columbus, Ohio, United States, 43129
      • Zangmeister Cancer Center / Sarah Cannon Research Institute
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital: North Campus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
    • Portland, Oregon, United States, 97227
      • Northwest Cancer Specialist, P.C.
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital of Rhode Island Oncology Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology / Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78745
      • Texas Oncology-South Austin
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Dallas Presbyterian
    • The Woodlands, Texas, United States, 77380
      • Texas Oncology
  • Virginia
    • Gainesville, Virginia, United States, 20155
      • Virginia Cancer Specialists, PC
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology & Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Patients ≥ 18 years of age
2. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
3. Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer
4. Patients must have platinum-sensitive disease defined as radiographic progression greater than 6 months from last dose of most recent platinum therapy Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression
5. Patients must have progressed radiographically on or after their most recent line of anticancer therapy
6. Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
7. Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity
8. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay

9. Prior anticancer therapy

   1. Patients must have received at least 2 prior systemic lines of platinum therapy and be considered by the Investigator as appropriate for single-agent non-platinum therapy (documentation required - eg, high risk of hypersensitivity reaction; risk of further cumulative toxicity with additional platinum, including but not limited to myelosuppression, neuropathy, renal insufficiency or other) i. Note: Patients who have had a documented platinum allergy may have had only 1 prior line of platinum
   2. Patients may have received up to but no more than 1 prior independent non-platinum cytotoxic therapy
   3. Patients must have had testing for breast cancer susceptibility gene (BRCA) mutation (tumor or germline) and, if positive, must have received a prior poly (ADP-ribose) polymerase ( (PARP) inhibitor as either treatment or maintenance therapy
   4. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy
   5. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently)
   6. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)

10. Patients must have completed prior therapy within the specified times below:

    1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
    2. Focal radiation completed at least 2 weeks prior to first dose of MIRV
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
12. Patients must have completed any major surgery at least 4 weeks prior to first dose of MIRV and have recovered or stabilized from the side effects of prior surgery prior to first dose of MIRV

13. Patients must have adequate hematologic, liver and kidney functions defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1500/μL) without granulocyte colony-stimulating factor (G-CSF) in the prior 10 days or long-acting white blood cell (WBC) growth factors in the prior 20 days
    2. Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
    7. Serum albumin ≥ 2 g/dL
14. Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for at least 3 months after the last dose
16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Key Exclusion Criteria-

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
2. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
3. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
4. Patients with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and/or monocular vision

5. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
   2. HIV infection
   3. Active cytomegalovirus infection
   4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV

   Note: Testing at screening is not required for the above infections unless clinically indicated.

6. Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

7. Patients with clinically significant cardiac disease including, but not limited to, any of the following:

   1. Myocardial infarction ≤ 6 months prior to first dose
   2. Unstable angina pectoris
   3. Uncontrolled congestive heart failure (New York Heart Association > class II)
   4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
   5. Uncontrolled cardiac arrhythmias
8. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
9. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
10. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
11. Patients requiring use of folate-containing supplements (eg, folate deficiency)
12. Patients with prior hypersensitivity to monoclonal antibodies (mAb)
13. Women who are pregnant or breastfeeding
14. Patients who received prior treatment with MIRV or other FRα-targeting agents
15. Patients with untreated or symptomatic central nervous system (CNS) metastases

16. Patients with a history of other malignancy within 3 years prior to enrollment

    Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible.

17. Prior known hypersensitivity reactions to study drugs and/or any of their excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mirvetuximab Soravtansine; Participants will receive MIRV 6.0 mg/kg adjusted by ideal body weight (AIBW)	Drug: Mirvetuximab soravtansine; Administered by intravenous (IV) infusion on Day 1 of every 3-week cycle; Other Names: IMGN853; MIRV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Objective Response Rate	Objective response rate (ORR), which includes confirmed best response of complete response (CR) or partial response (PR) as assessed by the Investigator	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess Duration of response (DOR)	Duration of response (DOR), defined as the time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator	up to 2 years
Assess treatment emergent adverse events (TEAEs)	Adverse Events (AE's) will be evaluated according to the NCI CTCAE v5.0. AEs will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term	up to 2 years
Assess Cancer Antigen-125	Cancer Antigen-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria	up to 2 years
Assess Progression-free survival (PFS)	Progression-free survival (PFS), defined as the time from first dose of MIRV until Investigator-assessed radiological PD or death, whichever occurs first	up to 2 years
Assess Overall survival (OS)	Overall survival (OS), defined as the time from first dose of MIRV until death	up to 2 years
Sensitivity analysis	ORR, DOR, and PFS by blinded independent central review (BICR) will be summarized as sensitivity analysis	up to 2 years

Collaborators and Investigators

• Sponsor: ImmunoGen, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2021
• Primary Completion (Actual): January 17, 2024
• Study Completion (Estimated): December 13, 2024

Study Registration Dates

• First Submitted: August 24, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Estimated): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Ovarian cancer; Folate-receptor alpha expression; Antibody-drug conjugate; Platinum-sensitive; Ovarian Neoplasma; High-Grade Ovarian; Recurrent Platinum-Sensitive,; PICCOLO
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Hypersensitivity; Ovarian Neoplasms; Fallopian Tube Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Maytansine; Mirvetuximab soravtansine
• Other Study ID Numbers: IMGN853419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No