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

• ClinicalTrials.gov Identifier: NCT05041257
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2021
• Last Update Posted: April 24, 2023
• Sponsor: ImmunoGen, Inc.
• Information provided by (Responsible Party): ImmunoGen, Inc.

Tracking Information

• First Submitted Date: August 24, 2021
• First Posted Date: September 13, 2021
• Last Update Posted Date: April 24, 2023
• Actual Study Start Date: August 31, 2021
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2021)

Assess Objective Response Rate [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Ovarian Cancer
• Peritoneal Cancer
• Fallopian Tube Cancer

Intervention

Drug: Mirvetuximab soravtansine

Administered by intravenous (IV) infusion on Day 1 of every 3-week cycle

Other Names:

• MIRV
• IMGN853

Study Arms

Experimental: Mirvetuximab Soravtansine

Participants will receive MIRV 6.0 mg/kg adjusted by ideal body weight (AIBW)

Intervention: Drug: Mirvetuximab soravtansine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 21, 2023): 79
• Original Estimated Enrollment (submitted: September 1, 2021): 75
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, France, Ireland, Italy, Spain, United States

Administrative Information

• NCT Number: NCT05041257
• Other Study ID Numbers: IMGN853419
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ImmunoGen, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ImmunoGen, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ImmunoGen, Inc.
• Verification Date: April 2023