A study to evaluate dosing schedules of mirvetuximab soravtansine in patients with epithelial ovarian, primary peritoneal, or fallopian tube cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Oct 2025 → ongoing

Decision date (initial)

2025-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AbbVie, Inc.

External identifiers

EU CT number

2024-517184-23-00

ClinicalTrials.gov

NCT06682988

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Randomized Phase 2 Cohort
• To characterize the safety of the alternative dosing schedule and the US-approved dosing schedule (mirvetuximab 6 mg/kg AIBW administered once every 3 weeks of a 21-day cycle)
• To evaluate efficacy parameters of the alternative dosing schedule and the US approved dosing schedule (mirvetuximab 6 mg/kg AIBW administered once every 3 weeks of a 21-day cycle)
Hepatic Impairment Cohort
• To determine the starting dose of MIRV in patients with moderate hepatic impairment

Secondary objectives 6

1. To investigate the frequency of ocular disorders, peripheral neuropathy, infusion reactions, and pneumonitis with 2 schedules of administration of MIRV
2. To investigate the safety profiles of 2 schedules of administration of MIRV
3. To evaluate additional measures of clinical efficacy with 2 schedules of administration of MIRV
4. To characterize the pharmacokinetics (PK) of MIRV in the alternative dosing schedule, compare PK with the US-approved dosing schedule, and reassess the existing exposure-response (ER) models
5. To assess doses based on body surface area (BSA) that are equivalent to doses based on adjusted ideal body weight (AIBW)
6. To determine the safety profile of MIRV in patients with moderate hepatic impairment

Conditions and MedDRA coding

platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers.

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001921-PIP01-16

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.To learn more about the process, or to submit a request, visit https://www.abbvieclinicaltrials.com/hcp/data-sharing/For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Patients ≥ 18 years of age.
2. Patient’s time from last date of prior therapy: a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter). b. Focal radiation completed ≥ 2 weeks prior to first dose of study treatment.
3. Patients with stabilized or recovered (Grade < 1) prior therapy-related toxicities.
4. Patients with prior major surgery are ≥ 4 weeks post-surgery prior to first dose of study treatment and have recovered or stabilized from the side effects of prior surgery.
5. Patients or their legally authorized representative are willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements.
6. Females of childbearing potential (FCBP) agree to use highly effective contraceptive method(s) (as defined in Section 5.8.7) while on study treatment and for ≥ 7 months after the last dose of study treatment.
7. A negative pregnancy test (serum or urine) for FCBP within 4 days prior to the first dose of study treatment.
8. Patients with a confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer.
9. Patients with platinum-resistant disease: a. Patients with 1 prior line of platinum-based therapy who have received ≥ 4 cycles of platinum and had a response (CR or PR) followed by radiological PD between > 3 months and ≤ 6 months after the date of the last dose of platinum. b. Patients with 2 or 3 prior lines of platinum-based therapy who had radiological PD ≤ 6 months after the date of the last dose of platinum. Note: PD is calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression. Note: Patients who have platinum-refractory disease following front-line treatment are excluded (see exclusion criteria).
10. Patients with PD diagnosed radiographically on or after their most recent line of therapy.
11. Patients treated with 1, 2, or 3 prior systemic lines of anticancer therapy, with the following clarifications: a. Adjuvant ± neoadjuvant is considered 1 line of therapy. b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) is considered part of the preceding line of therapy (ie, not counted independently). c. Therapy changed due to toxicity in the absence of progression is considered part of the same line (ie, not counted independently). d. Unless given as maintenance therapy, hormonal therapy is counted as a separate line of therapy.
12. Patients are 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.
13. Patients with a tumor that is positive for FRα expression as determined by the Ventana FOLR1 assay (≥ 75% of tumor staining at 2+ intensity).
14. Patients with ≥ 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
15. Patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
16. Patients with adequate hematologic, liver, and kidney function defined as follows: a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/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 b. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the prior 10 days c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 14 days d. Creatinine clearance (CrCl) ≥ 30 mL/min per the Cockcroft-Gault formula (Cockcroft 1976) e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN 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
17. Patients must have adequate hematologic and kidney function defined as follows: a. ANC ≥ 1.5 × 109/L (1500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days b. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the prior 10 days c. Hemoglobin ≥ 9.0 g/dL without PRBC transfusion in the prior 14 days d. Creatinine clearance (CrCl) ≥ 30 mL/min per the Cockcroft-Gault formula (Cockcroft 1976)
18. Patients must have moderate hepatic impairment according to NCI-ODWG criteria (total bilirubin > 1.5-3 × ULN [Mansfield 2016; see Appendix A for additional details]).

Exclusion criteria 20

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade or borderline ovarian tumor.
2. Patients with primary platinum-refractory disease, defined as disease that did not respond (CR or PR) or that progressed radiographically within 3 months of the last dose of first-line platinum-containing chemotherapy.
3. Patients with prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.
4. Patients with Grade > 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE).
5. Patients with the following ocular history and/or concurrent disorders: a. History of corneal transplantation b. Undergoing active postoperative management for refractive surgery, cataract surgery, corneal cross-linking, or corneal complications of surgery c. Confluent superficial punctate keratopathy (SPK) not expected to resolve to non-confluence or better within the screening window with standard of care intervention d. Active or chronic clinically significant (Grade ≥ 3) corneal dystrophy (eg, Fuchs dystrophy) e. Active ocular conditions requiring ongoing treatment/monitoring, such as glaucoma that is not adequately controlled with medication or surgery, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, or an ocular condition with high risk of retinal detachment f. Monocular vision with visual acuity in the better eye worse than 20/200 or visual fields less than 20 degrees (ie, functional blindness in both eyes)
6. 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 c. Active cytomegalovirus infection d. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study treatment 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 one of the following: a. Myocardial infarction ≤ 6 months prior to first dose b. Unstable angina pectoris c. Uncontrolled congestive heart failure (New York Heart Association > Class II) d. Uncontrolled Grade ≥ 3 hypertension (per CTCAE) e. Uncontrolled cardiac arrhythmias
9. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to randomization.
10. Patients with severe hepatic impairment according to NCI-ODWG criteria (Mansfield 2016; see Appendix A).
11. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease, including noninfectious pneumonitis.
12. Patients with required use of folate-containing supplements (eg, folate deficiency).
13. Patients with prior hypersensitivity to monoclonal antibodies.
14. Patients who are pregnant or lactating.
15. Patients with prior treatment with MIRV or other FRα-targeting agents.
16. Patients with untreated or symptomatic central nervous system (CNS) metastases.
17. Patients with a history of other malignancy within 3 years prior to randomization. Note: Does not include tumors with a negligible risk for metastasis or death (eg, adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or Stage IA Grade 1 endometrioid endometrial cancer).
18. Prior known hypersensitivity reactions to MIRV and/or any of its excipients.
19. People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship/curatorship), people who are unable to express their consent, and people who are subject to a legal guardianship order.
20. Simultaneous participation in another research study, in countries or localities where this is the health authority guidance.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Rates of Grade ≥ 2 treatment-emergent corneal AEs
2. Objective response rate (ORR), which includes a best response of confirmed complete response (CR) or partial response (PR), as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
3. PK parameters in patients with moderate hepatic impairment versus matching patients with normal hepatic function

Secondary endpoints 9

1. Rates of treatment-emergent all-grade ocular AEs, Grade ≥ 2 peripheral neuropathy, all-grade infusion reactions, and all-grade pneumonitis
2. Treatment-emergent adverse events (TEAEs) and changes in laboratory test results, physical examination (PE) results, and vital signs
3. 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
4. Progression-free survival (PFS), defined as the time from first dose of MIRV until investigator-assessed radiological PD or death, whichever occurs first
5. Overall survival (OS), defined as the time from first dose of MIRV until death
6. Cancer antigen 125 (CA-125) response rate per Gynecologic Cancer Intergroup (GCIG) criteria
7. PK parameters in both schedules, such as maximal concentration (Cmax), area under the concentration-time curve (AUC), trough concentration (Ctrough), volume of distribution at steady state (Vss), time to maximal concentration (Tmax), and terminal half-life (t½); relationships between efficacy/safety endpoints and exposure metrics; covariates on the ER relationships
8. Determine the differences in dose amount and exposure between the 2 schedules (BSA vs AIBW) and the effects on ER relationships
9. TEAEs and changes in laboratory test results, PE results, and vital signs

Investigational products

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

Test 1

Auxiliary 2

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 Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 10

Locations

4 EU/EEA countries · 33 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 30 files

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

Application history

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