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

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.

Key Facts

Interventions

Conditions

Eligibility

Inclusion Criteria:

1. Participants ≥ 18 years of age
2. Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
3. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer
4. Participants 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. Participants must have progressed radiographically on or after their most recent line of anticancer therapy
6. Participants must have at least 1 lesion that meets the definition of measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) (radiologically measured by the Investigator)
7. Participants 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. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
9. Prior anticancer therapy

   1. Participants 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 - for example, 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: Participants who have had a documented platinum allergy may have had only 1 prior line of platinum
   2. Participants may have received up to but no more than 1 prior independent non-platinum cytotoxic therapy
   3. Participants 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 (for example, bevacizumab, PARP inhibitors) will be considered part of the preceding line of therapy (that is, not counted independently)
   6. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (that is, not counted independently)
10. Participants 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. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
12. Participants 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. Participants must have adequate hematologic, liver and kidney functions defined as:

    1. Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/liter (L) (1500/microliter \[μL\]) 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 grams (g)/deciliter (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 (participants with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN)
    7. Serum albumin ≥ 2 g/dL
14. Participants 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

Exclusion Criteria:

1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/ borderline ovarian tumor
2. Participants with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
3. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
4. Participants 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. Participants 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. Human immunodeficiency virus (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. Participants with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
7. Participants 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. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
9. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
10. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
11. Participants requiring use of folate-containing supplements (for example, folate deficiency)
12. Participants with prior hypersensitivity to monoclonal antibodies (mAb)
13. Women who are pregnant or breastfeeding
14. Participants who received prior treatment with MIRV or other FRα-targeting agents
15. Participants with untreated or symptomatic central nervous system (CNS) metastases
16. Participants with a history of other malignancy within 3 years prior to enrollment

    Note: Participants with tumors with a negligible risk for metastasis or death (for example, 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

Outcome Measures

Locations

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