IMGN853 With Carboplatin in Second-line Treatment of FRα Expressing, Platinum-sensitive Epithelial Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT05456685
• Recruitment Status: Recruiting
• First Posted: July 13, 2022
• Last Update Posted: November 14, 2022
• Sponsor: ImmunoGen, Inc.
• Information provided by (Responsible Party): ImmunoGen, Inc.

Study Description

Brief Summary:

IMGN853-0420 is a multicenter, open-label, phase 2 study of carboplatin plus mirvetuximab soravtansine followed by mirvetuximab soravtansine continuation in folate receptor-alpha positive, recurrent platinum sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer following 1 prior line of platinum-based chemotherapy.

Condition or disease	Intervention/treatment	Phase
High Grade Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer	Drug: Mirvetuximab soravtansine; Drug: Carboplatin	Phase 2

Detailed Description:

This Phase 2 study is designed to evaluate the efficacy and safety of MIRV in combination with carboplatin followed by MIRV continuation in FRα-positive patients with recurrent platinum-sensitive ovarian cancer (PSOC) following 1 prior line of platinum-based chemotherapy. Upon completion of carboplatin plus MIRV combination chemotherapy (6 cycles), patients without progressive disease will continue on single-agent MIRV. Patients must have confirmation of FRα positivity by the Ventana FOLR1 Assay.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 114 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: Open-label study with treatment cycles every three weeks. All patients will receive 6 cycles of carboplatin (AUC5) + mirvetuximab soravtansine [6mg/kg of adjusted ideal body weight (AIBW)]. If patients have no PD at the end of the combination treatment, they will continue to maintenance mirvetuximab soravtansine (6 mg/kg of AIBW) as a single agent.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multicenter, Open-label, ph 2 Study of Carboplatin Plus Mirvetuximab Soravtansine Followed by Mirvetuximab Soravtansine Continuation in FRα Positive, Recurrent Platinum-sensitive, High-grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Following 1 Prior Line of Platinum-based Chemotherapy
• Actual Study Start Date: September 28, 2022
• Estimated Primary Completion Date: June 30, 2024
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm

Intervention/treatment

Experimental: Open Label; On Day 1 of every 3-week cycle (Q3W) for 6 cycles, MIRV will be given at the dosage of 6 mg/kg of adjusted ideal body weight (AIBW) along with carboplatin given at area under the concentration curve (AUC) 5 administered through intravenous (IV) infusion (maximum dosing per National Comprehensive Cancer Network [NCCN] guidelines [NCCN 2021]). Upon completion of carboplatin plus MIRV treatment, single-agent MIRV will be continued at the tolerated dose on Day 1 Q3W in patients with investigator determined stable disease, PR, or CR.

Drug: Mirvetuximab soravtansine; 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 FRα expression. FRα positivity will be defined by the Ventana FOLR1 Assay.; Other Names: IMGN853; MIRV; Drug: Carboplatin; Carboplatin is considered to be the treatment agent of choice in relapsed PSOC.

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]

   ORR following carboplatin plus MIRV combination as measured by the investigator and assessed according to RECIST v1.1, defined as the proportion of confirmed responders (complete response [CR] or partial response [PR]) among patients with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity who have measurable disease per RECIST v1.1 at inclusion.

   o ORR following carboplatin plus MIRV combination will also be measured, as a sensitivity analysis, by a BICR (blinded independent central review) in the same patient population.

Secondary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]

   ORR, defined as the proportion of confirmed responders (CR or PR) following carboplatin plus MIRV combination, as measured by the investigator and assessed according to RECIST v1.1, among patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity who have measurable disease per RECIST v1.1 at inclusion

   o ORR will also be measured by a BICR, as a sensitivity analysis, in the same patient population.

2. Duration of Response (DOR) [ Time Frame: Up to 3 years ]

   DOR, defined as the time from first response to radiological progressive disease (PD) or death, whichever occurs first, following carboplatin plus MIRV followed by MIRV continuation by the investigator and assessed according to RECIST v1.1 among efficacy evaluable patients:

   • with FRα expression of ≥ 50% of tumor cells with PS2+ staining and
   • with FRα expression of ≥ 25% of tumor cells with PS2+ staining
   • DOR in the above population will also be measured by BICR
3. Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]

   PFS as measured by the investigator and by BICR in patients with

   • FRα expression of ≥ 50% of tumor cells with PS2+ staining and
   • FRα expression of ≥ 25% of tumor cells with PS2+ staining
4. Overall Survival (OS) [ Time Frame: Up to 3 years ]

   OS in patients with

   • FRα expression of ≥ 50% of tumor cells with PS2+ staining and
   • FRα of ≥ 25% of tumor cells with PS2+ staining
5. CA-125 Response [ Time Frame: Up to 3 years ]

   CA-125 response as measured by the investigator, per GCIG, in the efficacy evaluable patients with

   • FRα expression of ≥ 50% of tumor cells with PS2+ staining and
   • FRα expression of ≥ 25% of tumor cells with PS2+ staining
6. Safety Parameters [ Time Frame: Up to 3 years ]
   Treatment-emergent adverse events and laboratory test results, physical examination, or vital signs

Other Outcome Measures:

1. Correlate biomarker levels with response to treatment [ Time Frame: Up to 3 years ]
   • Correlate soluble FRα levels and other blood-based biomarkers with response to carboplatin plus MIRV treatment
   • Correlate tumor-based biomarkers and gene mutations with response to carboplatin plus MIRV combination
2. Correlate response in patients with prior PARPi use [ Time Frame: Up to 3 years ]
   • Correlate response to carboplatin plus MIRV in patients following PARP inhibitor use
3. Incidence of seroconversion [ Time Frame: Up to 3 years ]
   • Identify incidence of seroconversion of anti-drug antibodies (ADA) to MIRV when given in combination with carboplatin and
   • Identify association with carboplatin plus MIRV safety and efficacy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients must be ≥ 18 years of age.
2. Patients must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1.
3. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
4. Patients must have relapsed after 1 prior line of platinum-based chemotherapy.

5. Patients must have platinum-sensitive disease defined as radiographic progression greater than 6 months from last dose of platinum-based chemotherapy.

   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.

6. Prior BRCA testing on the tumor or prior germline testing is required for eligibility. If not done prior, tumor or germline testing will need to be done at study entry. Somatic and germline BRCA-positive patients must have received prior treatment with a PARPi.
7. Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
8. Patients must 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; FRα-expressing tumors will be defined and classified by the Ventana FOLR1 Assay into low, medium, and high expressions defined as 25%-49%, 50%-74%, and ≥ 75% of tumor cells with PS2+ staining intensity, respectively. Patients must have confirmation of FRα positivity of ≥ 25% of tumor staining at ≥ 2+ intensity for entry into the study.
9. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia) and have discontinued any maintenance therapy at least 4 weeks before the first dose of carboplatin plus MIRV.
10. Patients must have completed any major surgery at least 4 weeks before the first dose of carboplatin plus MIRV and have recovered or stabilized from the side effects of prior surgery before the first dose of carboplatin plus MIRV.

11. Patients must have adequate hematologic, liver, and kidney functions defined as:

    1. Absolute neutrophil count ≥ 1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor or long-acting white blood cell growth factors in the 10 days prior to the C1D1 dose
    2. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the 10 days prior to the C1D1 dose
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell transfusion in the 14 days prior to the C1D1 dose
    4. Serum creatinine ≤ 1.5 × ULN
    5. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 × ULN
    6. Serum bilirubin ≤ 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN)
    7. Serum albumin ≥ 2 g/dL
12. Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
13. Females of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) while on study medication and for at least 3 months after the last dose of MIRV and 6 months after the last dose of carboplatin.
14. FCBP must have a negative pregnancy test within the 4 days prior to the C1D1 dose.

Exclusion Criteria:

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above types, or low-grade/borderline ovarian tumor

2. More than one line of prior chemotherapy. Lines of prior anticancer therapy are counted with the following considerations:

   1. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
   2. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently).
3. Patients with prior wide-field radiotherapy affecting at least 20% of the bone marrow
4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
5. 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, or monocular vision

6. 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 carboplatin plus MIRV Note: Testing at screening is not required for the above infections unless clinically indicated.
7. Patients with a history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

8. 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
9. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
10. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
11. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis (exception: Grade 1 noninfectious pneumonitis diagnosed on or within 6 weeks after treatment with an immunotherapeutic agent used in the treatment of their malignancy that has resolved per investigator or resolution of the radiologic findings)
12. Patients requiring use of folate-containing supplements (eg, folate deficiency)
13. Patients with prior hypersensitivity to monoclonal antibodies (mAb)
14. Females who are pregnant or breastfeeding
15. Patients who received prior treatment with MIRV or other FRα-targeting agents
16. Patients with untreated or symptomatic central nervous system metastases
17. Patients with a history of other malignancy within 3 years before 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.
18. Prior known hypersensitivity reactions to study drugs or any of their excipients

Contacts and Locations

Contacts

Contact: ImmunoGen, Inc.; 781-895-0600; medicalaffairs@immunogen.com

Contact: Michael Method, MD; +1-781-902-4673; Michael.Method@immunogen.com

Locations

United States, California

Women's Cancer Research Network; Recruiting

Fresno, California, United States, 93710

Contact: Christopher R Perkins, MD 559-438-7390

Principal Investigator: Christopher Perkins, MD

United States, New Jersey

Holy Name Medical Center; Recruiting

Teaneck, New Jersey, United States, 07666

Contact: Sharyn Lewin, MD, FACS 201-227-6200

Principal Investigator: Sharyn Lewin, MD, FACS

United States, New Mexico

New Mexico Cancer Care Alliance / University of New Mexico CCC; Recruiting

Albuquerque, New Mexico, United States, 87102

Contact: Colleen McCormick, MD 505-272-7799 ccmccormick@salud.unm.edu

Principal Investigator: Colleen McCormick, MD

Sponsors and Collaborators

ImmunoGen, Inc.

Investigators

• Principal Investigator: Gottfried Konecny, MD; University of California, Los Angeles

More Information

• Responsible Party: ImmunoGen, Inc.
• ClinicalTrials.gov Identifier: NCT05456685
• Other Study ID Numbers: IMGN853-0420; 2022-002034-14 ( EudraCT Number )
• First Posted: July 13, 2022
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

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

Keywords provided by ImmunoGen, Inc.:

platinum sensitive, folate-receptor alpha expression, antibody-drug conjugate, cancer, ovarian neoplasm, high-grade ovarian

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Hypersensitivity; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Fallopian Tube Diseases; Immune System Diseases; Carboplatin; Maytansine; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action