Brief Title
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)
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Assess Objective Response Rate
Secondary Outcome
Assess Duration of response (DOR)
Condition
Ovarian Cancer
Intervention
Mirvetuximab soravtansine
Study Arms / Comparison Groups
Mirvetuximab Soravtansine
Description: Participants will receive MIRV 6.0 mg/kg adjusted by ideal body weight (AIBW)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
75
Start Date
August 31, 2021
Completion Date
May 31, 2024
Primary Completion Date
May 31, 2023
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 anticancer therapy
including at least 2 prior lines of therapy containing a platinum, and be
considered by Investigator as appropriate for single-agent non-platinum therapy
(documentation required regarding reason[s] that patient is not appropriate for
further platinum therapy - eg, high risk of hypersensitivity reaction given prior
cumulative exposure to platinum; risk of further cumulative toxicity with
additional platinum, including but not limited to myelosuppression, neuropathy,
renal insufficiency) Note: Patients who have had a documented platinum allergy
may have had only 1 prior line of platinum
2. 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
3. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy
4. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered part of
the preceding line of therapy (ie, not counted independently)
5. Therapy changed due to toxicity in the absence of progression will be considered
part of the same line (ie, not counted independently)
6. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance
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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 781-895-0600, [email protected]
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT05041257
Organization ID
IMGN853419
Responsible Party
Sponsor
Study Sponsor
ImmunoGen, Inc.
Study Sponsor
, ,
Verification Date
June 2022