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

Ovarian Cancer Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05041257
• Other study ID #: IMGN853419
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 31, 2021
• Est. completion date: December 13, 2024

Study information

• Verified date: April 2024
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 79
• Est. completion date: December 13, 2024
• Est. primary completion date: January 17, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 FRa positivity

8. Patient's tumor must be positive for FRa 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 FRa-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

Related Conditions & MeSH terms

• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Hypersensitivity
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cancer

Intervention

Drug:
• Mirvetuximab soravtansine
Administered by intravenous (IV) infusion on Day 1 of every 3-week cycle

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Cabrini Hospital Malvern	Malvern	Victoria
Australia	Newcastle Private Hospital	New Lambton Heights	New South Wales
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	St John of God Subiaco Hospital	Subiaco	Western Australia
Australia	Burnside War Memorial Hospital - The Brian Fricker Oncology Centre	Toorak Gardens	South Australia
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHU UCL	Namur
Canada	McGill University Health Center	Montréal	Quebec
Canada	Ciussse-Chus	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre - University Health Network	Toronto	Ontario
France	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
Ireland	Bon Secours Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	University Hospital Waterford	Waterford
Italy	Azienda Ospedaliero-Universitaria-IRCCS	Bologna
Italy	Osperdale Cannizzaro di Catania	Catania
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
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	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Complejo Hospitalario Provincial de Castellón	Castelló
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital Universitario HU de Jaen	Jaen
Spain	Hospital de San Chinarro-Clara Campal	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital MD Anderson Cancer Center Madrid	Madrid
Spain	ClÃ-nica Universidad de Navarra (CUN)	Pamplona	Madrid
Spain	Virgen del Rocío	Sevilla
Spain	Hospital Clinico	Valencia
United States	Alaska Women's Cancer Care/Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Colorado School of Medicine	Aurora	Colorado
United States	Texas Oncology-South Austin	Austin	Texas
United States	The University of Alabama at Birmingham - Division of Gynecology Oncology O'Neal Comprehensive Cancer Center	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
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	Women's Cancer Center	Covington	Louisiana
United States	Texas Oncology - Dallas Presbyterian	Dallas	Texas
United States	City of Hope	Duarte	California
United States	Duke University	Durham	North Carolina
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Virginia Cancer Specialists, PC	Gainesville	Virginia
United States	Kadlec Clinic Hematology & Oncology	Kennewick	Washington
United States	UCLA-JCCC Dept of OBGYN - Women's Health Clinical Research Unit	Los Angeles	California
United States	Hillcrest Hospital: North Campus	Mayfield Heights	Ohio
United States	University of Miami	Miami	Florida
United States	Tennessee Oncology / Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Northwest Cancer Specialist, P.C.	Portland	Oregon
United States	Women & Infants Hospital of Rhode Island Oncology Research	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialist North Division	Saint Petersburg	Florida
United States	Maine Medical Partners - Women's Health	Scarborough	Maine
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Florida Cancer Specialists - Panhandle	Tallahassee	Florida
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	Texas Oncology	The Woodlands	Texas
United States	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona
United States	Florida Cancer Specialist East Division	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Ireland,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Assess Cancer Antigen-125	Cancer Antigen-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria	up to 2 years
Secondary	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
Secondary	Assess Overall survival (OS)	Overall survival (OS), defined as the time from first dose of MIRV until death	up to 2 years
Secondary	Sensitivity analysis	ORR, DOR, and PFS by blinded independent central review (BICR) will be summarized as sensitivity analysis	up to 2 years