A Randomized Phase 2 Study of Ocular Toxicity Evaluation and Mitigation During Treatment with Mirvetuximab Soravtansine in Patients with Recurrent Ovarian Cancer with High Folate Receptor-Alpha Expression

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Nov 2024 → ongoing

Decision date (initial)

2024-07-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Immunogen, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy, Safety, Efficacy, Pharmacokinetic

To assess the incidence rate and severity of MIRV-related corneal treatment-emergent adverse events (TEAEs) (≥ Grade 2) on prospective ophthalmic assessment in asymptomatic patients with recurrent ovarian cancer with high folate receptor alpha (FRα) expression receiving MIRV.

Secondary objectives 7

1. To assess the incidence rate and severity of ocular symptom TEAEs in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis
2. To assess the incidence rate and severity of MIRV-related corneal TEAEs (≥ Grade 2) symptomatic patients
3. To assess the incidence rate and severity of MIRV-related corneal TEAEs (≥ Grade 2) in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis
4. To evaluate and describe ocular health-related quality of life (HRQoL) in patients receiving MIRV using the composite score of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25)
5. To evaluate the pharmacokinetics (PK) of MIRV to assess exposure in symptomatic versus asymptomatic patients in both prophylaxis groups
6. To assess the incidence rate and allseverity of ocular exam TEAEs in asymptomatic and symptomatic patients
7. To assess the incidence rate and severity of ocular exam TEAEs in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis

Conditions and MedDRA coding

Recurrent Ovarian Cancer with High Folate Receptor-Alpha Expression

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001921-PIP01-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patients ≥ 18 years of age or age of maturity as per local law
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 epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer (collectively referred to as EOC hereafter) with high FRα expression
4. Patient's tumor must be FRα positive (FRα high) as defined by either the VENTANA FOLR1 (FOLR-2.1) IUO Assay or VENTANA FOLR1 (FOLR1-2.1) RxDx Assay (hereafter collectively termed Ventana FOLR1 Assay) (≥75% cells exhibit 2 or 3+ membrane staining intensity)
5. Patients must have recurrent ovarian cancer that may be platinum-resistant or platinum-sensitive as defined below). - Platinum-resistant disease: a. Patients who have only had 1 line of platinum-based therapy must have received ≥ 4 cycles of platinum, must have had a disease response (complete response [CR], partial response [PR], or no evaluable disease after surgery with neoadjuvant/adjuvant therapy), and then had disease progression > 3 months and < 6 months after the date of the last dose of platinum; b. Patients who have received 2 to 4 lines of platinum therapy must have progressed during or < 6 months after the date of the last dose of platinum; c. Patients with primary platinum-refractory disease (disease progression ≤ 3 months from last dose of platinum of first line of treatment) will not be eligible. - Platinum-sensitive disease: d. Patients with platinum-sensitive disease are defined as radiographic progression ≥ 6 months from the last dose of the most recent platinum therapy; e. Patients’ disease must have progressed radiographically on (non-platinum only) or after their most recent line of anticancer therapy.
6. Patients with known breast cancer susceptibility gene mutations (tumor or germline) must have received poly adenosine diphosphate ribose polymerase inhibitors (PARPi).
7. With regard to prior anticancer therapy: a. Neoadjuvant ± adjuvant therapies are considered 1 line of therapy; b. Maintenance therapy (eg, bevacizumab, PARPi) will be considered part of the preceding line of therapy (ie, not counted independently); c. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (ie, not counted independently); d. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance. 7.1 Requirements for prior anticancer therapy (PSOC patients ONLY): a. Patients must have received ≥ 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). 7.2 Requirements for prior anticancer therapy (PROC patients ONLY): a. Patients must have received ≥1 line but no more than 4 prior systemic lines of anticancer therapy and must be considered by the investigator as appropriate for single-agent therapy as the next line of treatment.
8. Patients must have completed prior therapy within the specified times below: a. Systemic antineoplastic therapy ≥ 5 half-lives or 4 weeks (whichever is shorter) before the first dose of MIRV; b. Focal radiation completed ≥ 2 weeks before the the first dose of MIRV.
9. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
10. Patients must have completed any major surgery ≥ 4 weeks before the first dose of MIRV and have recovered or stabilized from the side effects of prior surgery before the first dose of MIRV.
11. Patients must have adequate hematologic, liver, and kidney functions, defined as: a. Absolute neutrophil count ≥ 1.5 × 109/L (1500 cells/μL) without granulocyte colony-stimulating factor in the previous 10 days or long-acting white blood cell growth factors in the previous 20 days; b. Platelet count ≥ 100 × 109/L (100,000 cells/μL) without platelet transfusion in the previous 10 days; c. Hemoglobin ≥ 8.0 g/dL without packed red blood cell transfusion in the previous 7 days; Note: Erythropoietin is allowed. d. Creatinine clearance ≥ 30 mL/min per the Cockcroft-Gault formula; e. Aspartate aminotransferase and alanine aminotransferase ≤ 3.0× ULN (upper limit of normal); f. Serum bilirubin ≤ 1.5 × ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 × ULN); g. Serum albumin ≥ 2 g/dL.
12. Patients must be willing and able to sign the informed consent form (ICF) and adhere to the protocol requirements
13. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for ≥ 7 months after the last dose.
14. WOCBP must have a negative pregnancy test ≤ 4 days before the first dose of MIRV
15. The following requirements are for patients who are HIV seropositive: a. On established highly active antiretroviral therapy (HAART) for ≥ 12 weeks with an HIV viral load of less than 200 copies/mL, HAART is a requirement for the duration of the study. The specific agents are at the discretion of the investigator; b. Cluster of differentiation 4 (CD4+) T cell counts ≥ 400 cell/μL; c. No AIDS-defining opportunistic infection within the past 12 months

Exclusion criteria 17

1. Patients with borderline ovarian tumor or non-epithelial histology or mixed histology, including borderline or non-epithelial histology will be excluded
2. Patients with clinically significant comorbid conditions, including but not limited to any of the following: a. Myocardial infarction ≤ 6 months before first dose; b. Unstable angina pectoris; c. Uncontrolled congestive heart failure (New York Heart Association > Class II); d. Uncontrolled ≥ Grade 3 hypertension (per NCI-CTCAE v5.0); e. Uncontrolled cardiac arrhythmias; f. Patients with a history of hemorrhagic or ischemic stroke ≤ 6 months before enrollment; g. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C); h. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis or evidence of ILD/pneumonitis on baseline chest CT; i. Patients with medical conditions requiring use of folate-containing supplements (eg, folate deficiency).
3. Patients with prior hypersensitivity to monoclonal antibodies (mAbs)
4. Patients who are pregnant or breastfeeding
5. Patients who received prior treatment with MIRV or other FRα-targeting agents
6. Patients with untreated or symptomatic central nervous system metastases
7. Patients with a history of other malignancy ≤ 2 years before enrollment
8. Patients with a prior known hypersensitivity reaction to study drugs or any of their excipients
9. PROC patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR), or progressed within ≤ 3 months of the last dose of first line platinum-containing chemotherapy
10. Patients with prior wide-field radiotherapy (RT) affecting ≥ 20% of the bone marrow
11. Patients with > Grade 1 peripheral neuropathy per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0)
12. Patients with significant active or chronic corneal disorders (eg, corneal dystrophies, degenerations, limbal stem cell deficiency), history of corneal transplantation, significant ocular inflammatory conditions (eg, active or recurrent uveitis), or other active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, active diabetic retinopathy with macular edema, macular degeneration requiring treatment ≤ 90 days before the first dose, presence of papilledema, BCVA worse than 20/70 in either eye, or monocular vision.
13. Patients receiving corticosteroid or vasoconstricting eye drops at baseline or within 5 weeks of C1D1
14. Patients who are ineligible to receive either brimonidine or corticosteroid eye drop
15. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following: a. Active hepatitis B or C infection (whether or not on active antiviral therapy); b. HIV infection (if inclusion criteria #15 is not met) c. Active cytomegalovirus infection; d. Any other concurrent infectious disease requiring intravenous (IV) antibiotics ≤ 2 weeks before the first dose of MIRV
16. Patients with a history of multiple sclerosis or other demyelinating disease or Lambert-Eaton syndrome (paraneoplastic syndrome).
17. Patients with medical conditions requiring chronic systemic corticosteroids, including those requiring low physiologic doses. Patients requiring topical, inhaled, and/or intranasal corticosteroid therapy are eligible.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The incidence rate and severity of MIRV-related corneal TEAEs (≥ Grade 2) in asymptomatic patients (defined as ocular symptom assessment ≤ Grade 1) with recurrent ovarian cancer with high FRα expression, assessed up to 18 weeks from Cycle 1 Day 1 (C1D1) or at the 30-Day Follow-up visit, whichever is earlier

Secondary endpoints 7

1. The incidence rate and severity of ocular symptom TEAEs in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis assessed up to 18 weeks from C1D1 or at the 30-Day Follow-up visit, whichever is earlier
2. The incidence rate and severity of MIRV-related corneal TEAEs (≥ Grade 2) in symptomatic patients on ophthalmic assessment up to 18 weeks from C1D1 or at the 30-Day Follow-up visit, whichever is earlier
3. The incidence rate and severity of all MIRV-related corneal TEAEs (≥ Grade 2) in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis assessed up to 18 weeks from C1D1 or at the 30-Day Follow-up, whichever is earlier
4. Use of the composite score of the NEI VFQ-25 to evaluate ocular HRQoL and patient-reported outcomes at C5D1 or at the 30-Day Follow-up visit, whichever is earlier
5. PK concentrations, including pre-dose and end-of-infusion plasma concentration in asymptomatic and symptomatic patients in both prophylaxis groups
6. The incidence rate and severity of ocular exam TEAEs in asymptomatic and symptomatic patients on ophthalmic assessment up to 18 weeks from C1D1 or at the 30-Day Follow-up visit, whichever is earlier
7. The incidence rate and severity of ocular exam TEAEs in patients using corticosteroid or vasoconstricting eye drop primary prophylaxis up to 18 weeks from C1D1 or at the 30‑Day Follow-up visit, whichever is earlier

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Third parties 1

Locations

4 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications