Clinical trial NCT05041257: Mirvetuximab Soravtansine Monotherapy in Platinum-Sensitive Epithelial, Peritoneal, and Fallopian Tube Cancers (PICCOLO)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Keywords: Platinum-sensitive
Ovarian cancer
Folate-receptor alpha expression
Antibody-drug conjugate
Cancer
Ovarian Neoplasma
Recurrent Platinum-Sensitive,
High-Grade Ovarian
PICCOLO
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-09-13
Enrollment: 79
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Assess Objective Response Rate
timeFrame: up to 2 years
Secondary outcomes:
measure: Assess Duration of response (DOR)
timeFrame: up to 2 years
measure: Assess treatment emergent adverse events (TEAEs)
timeFrame: up to 2 years
measure: Assess Cancer Antigen-125
timeFrame: up to 2 years
measure: Assess Progression-free survival (PFS)
timeFrame: up to 2 years
measure: Assess Overall survival (OS)
timeFrame: up to 2 years
measure: Sensitivity analysis
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham - Division of Gynecology Oncology O'Neal Comprehensive Cancer Center
state: Alabama
city: Anchorage
country: United States
facility: Alaska Women's Cancer Care/Providence Alaska Medical Center
state: Alaska
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: UCLA-JCCC Dept of OBGYN - Women's Health Clinical Research Unit
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist North Division
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists - Panhandle
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialist East Division
state: Florida
city: Covington
country: United States
facility: Women's Cancer Center
state: Louisiana
city: Scarborough
country: United States
facility: Maine Medical Partners - Women's Health
state: Maine
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital-Moll Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Zangmeister Cancer Center / Sarah Cannon Research Institute
state: Ohio
city: Mayfield Heights
country: United States
facility: Hillcrest Hospital: North Campus
state: Ohio
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialist, P.C.
state: Oregon
city: Providence
country: United States
facility: Women & Infants Hospital of Rhode Island Oncology Research
state: Rhode Island
city: Nashville
country: United States
facility: Tennessee Oncology / Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-South Austin
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology
state: Texas
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology & Oncology
state: Washington
city: New Lambton Heights
country: Australia
facility: Newcastle Private Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Toorak Gardens
country: Australia
facility: Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Malvern
country: Australia
facility: Cabrini Hospital Malvern
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Namur
country: Belgium
facility: CHU UCL
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre - University Health Network
state: Ontario
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Sherbrooke
country: Canada
facility: Ciussse-Chus
state: Quebec
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Poali Calmette
city: Paris
country: France
facility: Groupe Hospitalier Diaconesse, Croix Saint-Simon
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Plerin
country: France
facility: Centre CARIO - HPCA
city: Saint-Herblain Cedex
country: France
facility: ICO Centre Rene Gauducheau
city: Strasbourg
country: France
facility: Institut de Cancerologie Strabsourg Europe Unité de recherche clinique
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria-IRCCS
city: Catania
country: Italy
facility: Osperdale Cannizzaro di Catania
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: IRCCS - Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Napoli
city: Ravenna
country: Italy
facility: Azienda Unita Sanitaria Locale di Ravenna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Pamplona
country: Spain
facility: ClÃ-nica Universidad de Navarra (CUN)
state: Madrid
city: Badalona
country: Spain
facility: Institut Català d'Oncologia - Hospital Universitari Germans Trias i Pujol, Unidad de Investigación Clínica, Servicio de Oncología, Institut Josep Carreres (IJC, 1ª planta)
city: Barcelona
country: Spain
facility: Vall d&#39;Hebron Institute of Oncology
city: Barcelona
country: Spain
facility: Institut Català d' Oncologia L' Hospitalet
city: Castelló
country: Spain
facility: Complejo Hospitalario Provincial de Castellón
city: Cordoba
country: Spain
facility: Hospital Reina Sofia
city: Jaen
country: Spain
facility: Hospital Universitario HU de Jaen
city: Madrid
country: Spain
facility: Hospital MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital de San Chinarro-Clara Campal
city: Madrid
country: Spain
facility: Hospital La Paz
city: Sevilla
country: Spain
facility: Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clinico
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: