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

Sponsor

ImmunoGen, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05041257

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

1.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer	Drug: Mirvetuximab soravtansine	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 31, 2021

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

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: MIRV IMGN853

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:

MIRV

IMGN853

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Patients ≥ 18 years of age
Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer
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
Patients must have progressed radiographically on or after their most recent line of anticancer therapy
Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
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
Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
Prior anticancer therapy
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
Patients may have received up to but no more than 1 prior independent non-platinum cytotoxic therapy
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
Neoadjuvant ± adjuvant therapies are considered 1 line of therapy
Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (ie, not counted independently)
Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently)
Patients must have completed prior therapy within the specified times below:
Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
Focal radiation completed at least 2 weeks prior to first dose of MIRV
Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
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
Patients must have adequate hematologic, liver and kidney functions defined as:
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
Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
Serum albumin ≥ 2 g/dL
Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
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
WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Key Exclusion Criteria-

Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
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
Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
Active hepatitis B or C infection (whether or not on active antiviral therapy)
HIV infection
Active cytomegalovirus infection
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.

Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
Patients with clinically significant cardiac disease including, but not limited to, any of the following:
Myocardial infarction ≤ 6 months prior to first dose
Unstable angina pectoris
Uncontrolled congestive heart failure (New York Heart Association > class II)
Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
Uncontrolled cardiac arrhythmias
Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
Patients requiring use of folate-containing supplements (eg, folate deficiency)
Patients with prior hypersensitivity to monoclonal antibodies (mAb)
Women who are pregnant or breastfeeding
Patients who received prior treatment with MIRV or other FRα-targeting agents
Patients with untreated or symptomatic central nervous system (CNS) metastases
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.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alaska Women's Cancer Care/Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
2	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85711
3	UCLA-JCCC Dept of OBGYN - Women's Health Clinical Research Unit	Los Angeles	California	United States	90095
4	University of Colorado School of Medicine	Aurora	Colorado	United States	80045
5	Yale University School of Medicine	New Haven	Connecticut	United States	06520-8063
6	Florida Cancer Specialists - South	Fort Myers	Florida	United States	33901
7	Florida Cancer Specialist North Division	Saint Petersburg	Florida	United States	33705
8	Florida Cancer Specialists - Panhandle	Tallahassee	Florida	United States	32308
9	Florida Cancer Specialist East Division	West Palm Beach	Florida	United States	33401
10	Women's Cancer Center	Covington	Louisiana	United States	70433
11	Maine Medical Partners - Women's Health	Scarborough	Maine	United States	04074
12	Tufts Medical Center	Boston	Massachusetts	United States	02111
13	Baystate Medical Center	Springfield	Massachusetts	United States	01199
14	Washington University School of Medicine	Saint Louis	Missouri	United States	63108
15	Holy Name Medical Center	Teaneck	New Jersey	United States	07666
16	Duke University	Durham	North Carolina	United States	27710
17	Cleveland Clinic Fairview Hospital-Moll Cancer Center	Cleveland	Ohio	United States	44111
18	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
19	Zangmeister Cancer Center / Sarah Cannon Research Institute	Columbus	Ohio	United States	43129
20	Hillcrest Hospital: North Campus	Mayfield Heights	Ohio	United States	44124
21	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
22	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
23	Northwest Cancer Specialist, P.C.	Portland	Oregon	United States	97227
24	Women & Infants Hospital of Rhode Island Oncology Research	Providence	Rhode Island	United States	02905
25	Tennessee Oncology / Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
26	Texas Oncology-South Austin	Austin	Texas	United States	78745
27	Texas Oncology - Dallas Presbyterian	Dallas	Texas	United States	75231
28	Texas Oncology	The Woodlands	Texas	United States	77380
29	Virginia Cancer Specialists, PC	Gainesville	Virginia	United States	20155
30	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
31	Kadlec Clinic Hematology & Oncology	Kennewick	Washington	United States	99336
32	Newcastle Private Hospital	New Lambton Heights	New South Wales	Australia	2305
33	Monash Health	Clayton	Victoria	Australia	3165
34	Cabrini Hospital Malvern	Malvern	Victoria	Australia	3144
35	St John of God Subiaco Hospital	Subiaco	Western Australia	Australia	6008
36	UZ Leuven	Leuven		Belgium	3000
37	CHU UCL	Namur		Belgium	5000
38	Princess Margaret Cancer Centre - University Health Network	Toronto	Ontario	Canada	M5G 2M9
39	Bon Secours Hospital	Cork		Ireland	00
40	St James's Hospital	Dublin		Ireland	D08 NHY1
41	Beaumont Hospital	Dublin		Ireland	D09 V2N0
42	University Hospital Waterford	Waterford		Ireland	X91 ER8E
43	Osperdale Cannizzaro di Catania	Catania		Italy	95126
44	Istituto Nazionale Tumori Napoli	Napoli		Italy	80131
45	Azienda Unita Sanitaria Locale di Ravenna	Ravenna		Italy	48100
46	Fondazione Policlinico Universitario A. Gemelli IRCCS	Roma		Italy	168
47	ClÃ-nica Universidad de Navarra (CUN)	Pamplona	Madrid	Spain	28027
48	Vall d'Hebron Institute of Oncology	Barcelona		Spain	08035
49	Complejo Hospitalario Provincial de Castellón	Castelló		Spain	12002
50	Hospital Reina Sofia	Cordoba		Spain	14004
51	Hospital Universitario HU de Jaen	Jaen		Spain	23007
52	Hospital MD Anderson Cancer Center Madrid	Madrid		Spain	28033
53	Hospital de San Chinarro-Clara Campal	Madrid		Spain	28050
54	Hospital La Paz	Madrid		Spain
55	Virgen del Rocío	Sevilla		Spain	41013
56	Hospital Clinico	Valencia		Spain