Evaluation of epithelial ovarian, primary peritoneal, or fallopian tube cancer treatment in first recurrance using platinum-based chemotherapy and the monoclonal antibody-drug conjugate “Mirvetuximab soravtansine”, followed by treatment with “Mirvetuximab soravtansine” alone in platinum-sensitive antibody-responder patients (folate receptor-alpha positive)

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

17 Oct 2023 → ongoing

Decision date (initial)

2023-11-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ImmunoGen, Inc.

External identifiers

EU CT number

2022-501220-14-00

ClinicalTrials.gov

NCT05456685

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety

To determine the objective response rate (ORR) of carboplatin plus MIRV, as assessed by the investigator, in efficacy evaluable patients with recurrent platinum-sensitive, high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer (PSOC) and with folate receptor-alpha (FRα) expression of ≥ 50% of tumor cells with staining at 2+ intensity (PS2+) following 1 prior line of platinum-based chemotherapy. The ORR of carboplatin plus MIRV will also be assessed, as a sensitivity ana≥lysis, by a blinded independent central review (BICR) in the same patient population.

Secondary objectives 1

1. • To determine the ORR of carboplatin plus MIRV, as assessed by the investigator, in efficacy evaluable patients with FRα expression of ≥ 25% of tumor cells with PS2+ staining intensity and with recurrent PSOC following 1 prior line of platinum-based chemotherapy. o The ORR of carboplatin plus MIRV will also be assessed, as a sensitivity analysis, by a BICR committee in the same patient population

Conditions and MedDRA coding

epithelial ovarian, primary peritoneal, or fallopian tube cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

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
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: a. 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 b. Platelet count ≥ 100 × 109/L (100,000/μL) without platelet transfusion in the 10 days prior to the C1D1 dose c. Hemoglobin ≥ 9.0 g/dL without packed red blood cell transfusion in the 14 days prior to the C1D1 dose d. Serum creatinine ≤ 1.5 × ULN e. Aspartate aminotransferase and alanine aminotransferase ≤ 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
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 18

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: a. 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. b. 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: 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 prior to the first dose of carboplatin plus MIRV
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: 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 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
18. Prior known hypersensitivity reactions to study drugs or any of their excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR following carboplatin plus MIRV combination as measured by the investigator and assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, defined as the proportion of confirmed responders among patients with FRα expression of ≥ 50% of tumor cells with PS2+ staining intensity who have measurable disease per RECIST v1.1 at inclusion

Secondary endpoints 1

1. 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 the 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.

Investigational products

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

Test 1

Auxiliary 4

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 12

Locations

3 EU/EEA countries · 19 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 29 files

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

Application history

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