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

Phase 2

Completed

• Conditions: Fallopian Tube Cancer; Ovarian Cancer; Peritoneal Cancer
• Interventions: Drug: Mirvetuximab soravtansine

• Registration Number: NCT05041257
• Lead Sponsor: AbbVie

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)

Study Timeline

• Study First Submitted: 2021-08-24
• Study Start: 2021-08-31
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-13
• Primary Completion: 2024-01-17
• Disposition First Posted: 2024-11-25
• Status Verified: 2024-12
• Disposition First Submitted: 2024-12-03
• Study Completion: 2024-12-12
• Last Update Submitted: 2024-12-18
• Last Update Posted: 2024-12-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 79

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

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Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mirvetuximab Soravtansine	Mirvetuximab soravtansine	Participants will receive MIRV 6.0 mg/kg adjusted by ideal body weight (AIBW)

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Assess Progression-free survival (PFS)	up to 2 years	Progression-free survival (PFS), defined as the time from first dose of MIRV until Investigator-assessed radiological PD or death, whichever occurs first
Assess Duration of response (DOR)	up to 2 years	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
Assess Overall survival (OS)	up to 2 years	Overall survival (OS), defined as the time from first dose of MIRV until death
Assess Cancer Antigen-125	up to 2 years	Cancer Antigen-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria
Sensitivity analysis	up to 2 years	ORR, DOR, and PFS by blinded independent central review (BICR) will be summarized as sensitivity analysis
Assess treatment emergent adverse events (TEAEs)	up to 2 years	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

Trial Locations

Locations (78)

City of Hope; 🇺🇸 Duarte, California, United States

The University of Alabama at Birmingham - Division of Gynecology Oncology O'Neal Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

Alaska Women's Cancer Care/Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Arizona Oncology Associates, PC - HOPE; 🇺🇸 Tucson, Arizona, United States

Vall d&#39;Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

UCLA-JCCC Dept of OBGYN - Women's Health Clinical Research Unit; 🇺🇸 Los Angeles, California, United States

Texas Oncology - Dallas Presbyterian; 🇺🇸 Dallas, Texas, United States

Texas Oncology; 🇺🇸 The Woodlands, Texas, United States

Osperdale Cannizzaro di Catania; 🇮🇹 Catania, Italy

University of Colorado School of Medicine; 🇺🇸 Aurora, Colorado, United States

Yale University School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Florida Cancer Specialists - South; 🇺🇸 Fort Myers, Florida, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Florida Cancer Specialist North Division; 🇺🇸 Saint Petersburg, Florida, United States

Florida Cancer Specialists - Panhandle; 🇺🇸 Tallahassee, Florida, United States

Florida Cancer Specialist East Division; 🇺🇸 West Palm Beach, Florida, United States

Women's Cancer Center; 🇺🇸 Covington, Louisiana, United States

Maine Medical Partners - Women's Health; 🇺🇸 Scarborough, Maine, United States

Tufts Medical Center; 🇺🇸 Boston, Massachusetts, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Holy Name Medical Center; 🇺🇸 Teaneck, New Jersey, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Cleveland Clinic Fairview Hospital-Moll Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Zangmeister Cancer Center / Sarah Cannon Research Institute; 🇺🇸 Columbus, Ohio, United States

Hillcrest Hospital: North Campus; 🇺🇸 Mayfield Heights, Ohio, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Willamette Valley Cancer Institute and Research Center; 🇺🇸 Eugene, Oregon, United States

Northwest Cancer Specialist, P.C.; 🇺🇸 Portland, Oregon, United States

Women & Infants Hospital of Rhode Island Oncology Research; 🇺🇸 Providence, Rhode Island, United States

Tennessee Oncology / Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology-South Austin; 🇺🇸 Austin, Texas, United States

Virginia Cancer Specialists, PC; 🇺🇸 Gainesville, Virginia, United States

Virginia Oncology Associates; 🇺🇸 Norfolk, Virginia, United States

Kadlec Clinic Hematology & Oncology; 🇺🇸 Kennewick, Washington, United States

Newcastle Private Hospital; 🇦🇺 New Lambton Heights, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 St. Leonards, New South Wales, Australia

Burnside War Memorial Hospital - The Brian Fricker Oncology Centre; 🇦🇺 Toorak Gardens, South Australia, Australia

Monash Health; 🇦🇺 Clayton, Victoria, Australia

Cabrini Hospital Malvern; 🇦🇺 Malvern, Victoria, Australia

St John of God Subiaco Hospital; 🇦🇺 Subiaco, Western Australia, Australia

UZ Gent; 🇧🇪 Gent, Belgium

UZ Leuven; 🇧🇪 Leuven, Belgium

CHU UCL; 🇧🇪 Namur, Belgium

Princess Margaret Cancer Centre - University Health Network; 🇨🇦 Toronto, Ontario, Canada

McGill University Health Center; 🇨🇦 Montréal, Quebec, Canada

Ciussse-Chus; 🇨🇦 Sherbrooke, Quebec, Canada

Centre Oscar Lambret; 🇫🇷 Lille, France

Centre Léon Bérard; 🇫🇷 Lyon, France

Institut Poali Calmette; 🇫🇷 Marseille, France

Groupe Hospitalier Diaconesse, Croix Saint-Simon; 🇫🇷 Paris, France

Centre Hospitalier Lyon Sud; 🇫🇷 Pierre-Bénite, France

Centre CARIO - HPCA; 🇫🇷 Plerin, France

ICO Centre Rene Gauducheau; 🇫🇷 Saint-Herblain Cedex, France

Institut de Cancerologie Strabsourg Europe Unité de recherche clinique; 🇫🇷 Strasbourg, France

Bon Secours Hospital; 🇮🇪 Cork, Ireland

St James's Hospital; 🇮🇪 Dublin, Ireland

Beaumont Hospital; 🇮🇪 Dublin, Ireland

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

University Hospital Waterford; 🇮🇪 Waterford, Ireland

Azienda Ospedaliero-Universitaria-IRCCS; 🇮🇹 Bologna, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milano, Italy

IRCCS - Istituto Europeo di Oncologia; 🇮🇹 Milano, Italy

Istituto Nazionale Tumori Napoli; 🇮🇹 Napoli, Italy

Azienda Unita Sanitaria Locale di Ravenna; 🇮🇹 Ravenna, Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS; 🇮🇹 Roma, Italy

ClÃ-nica Universidad de Navarra (CUN); 🇪🇸 Pamplona, Madrid, Spain

Institut Català d'Oncologia - Hospital Universitari Germans Trias i Pujol, Unidad de Investigación Clínica, Servicio de Oncología, Institut Josep Carreres (IJC, 1ª planta); 🇪🇸 Badalona, Spain

Institut Català d' Oncologia L' Hospitalet; 🇪🇸 Barcelona, Spain

Complejo Hospitalario Provincial de Castellón; 🇪🇸 Castelló, Spain

Hospital Reina Sofia; 🇪🇸 Cordoba, Spain

Hospital Universitario HU de Jaen; 🇪🇸 Jaen, Spain

Hospital MD Anderson Cancer Center Madrid; 🇪🇸 Madrid, Spain

Hospital de San Chinarro-Clara Campal; 🇪🇸 Madrid, Spain

Hospital La Paz; 🇪🇸 Madrid, Spain

Virgen del Rocío; 🇪🇸 Sevilla, Spain

Hospital Clinico; 🇪🇸 Valencia, Spain