A randomized phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy. supported by: DIAGNOSTIC PROTOCOL for the VENTANA FOLR1 (FOLR1-2.1) CDx Assay Ventana No. RD004881; Protocol Document No. D152967

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AGO Research GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Aug 2021 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516959-40-00

EudraCT number

2018-004207-39

ClinicalTrials.gov

NCT04274426

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier. PD is based on investigator assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Secondary objectives 8

1. Overall survival (OS), defined as the time from randomization to death from any cause.
2. Objective Response Rate (ORR)
3. Efficacy regarding PFS, OS and ORR depending on histologic subtype.
4. Time to serological progressive disease according to GCIG criteria.
5. Time to first subsequent treatment (TFST)
6. Time to second subsequent treatment (TSST)
7. Patient-reported outcomes: Quality of Life (EORTC C-30, OV28)
8. Safety and tolerability of the used drugs evaluated by NCI CTCAE v5.0, records of dose reductions, delays, or interruptions.

Conditions and MedDRA coding

This trial evaluates the efficacy and safety of Mirvetuximab soravtansine (IMGN853) plus Carboplatin chemotherapy in FRα high patients with recurrent ovarian cancer who are eligible for platinum-based chemotherapy.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. All patients must have a pathologically documented, definite diagnosis of epithelial cancer of the ovary, the fallopian tube or the peritoneum.
2. Relapsed disease with a platinum-free interval >3 months.
3. All histologic subtypes of ovarian carcinoma including carcinosarcoma (malignant mixed Mullerian tumors, MMMT).
4. Patients with wildtype BRCA1/2 mutation status or with a deleterious BRCA1/2 mutation in germline or somatic testing if they underwent PARP inhibitor therapy in previous treatment line.
5. Patients must be willing to provide archival tumor tissue from current relapse or previous surgeries/biopsies for central confirmation of FRα high status by PS2+ scoring: all tumors must exhibit ≥75% of tumor cells with FRα membrane staining and ≥ 2+ intensity by immunohistochemistry (IHC) using the Ventana FOLR1 (FOLR1 2.1) CDx assay.
6. Patients must have measurable disease or evaluable disease in combination with GCIG CA-125 criteria.
7. Patients had one or more prior lines of chemotherapy. The last line of chemotherapy must have included platinum (min. 4 cycles) and has resulted in a partial or complete response.
8. Major surgery (not including placement of vascular access device, tumor punch/scrape biopsies or secondary wound closure) must be completed four weeks prior to Day 1.
9. Patients must have adequate hematological, liver, cardiac and kidney function: a) Hemoglobin ≥ 10.0 g/dL. b) Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. c) Platelet count ≥ 100 x 109/L. d) Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). e) Aspartate aminotransferase/Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and Alanine aminotransferase/Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) ≤ 2.5 x ULN, unless liver metastases are present in which case they must be ≤ 5 x ULN. f) Serum creatinine ≤ 1.5 x institutional ULN and glomerular filtration rate of at least 40 ml/minute according to Cockroft-Gault formula.
10. Patient is female and ≥18 years of age at the time of the first screening visit.
11. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
12. Patients must be willing and able to sign the informed consent form, and to adhere to the study visit schedule and other protocol requirements.
13. Women of childbearing potential (a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy) must have a negative serum pregnancy test within 3 days from day 1 of cycle 1 and agree to use a highly effective method of contraception while on study treatment and respectively for at least 8 months after end of treatment. Such methods include: a) Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal b) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable c) Intrauterine device (IUD) d) Intrauterine hormone-releasing system (IUS) e) Bilateral tubal occlusion f) Vasectomized partner g) Sexual abstinence

Exclusion criteria 19

1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e. germ cell tumors).
2. Ovarian tumors of low malignant potential (e.g. borderline tumors).
3. Unknown BRCA status.
4. Patients who are planned to receive bevacizumab for the current relapse.
5. Other malignancy within the last 3 years (except cervix or breast in situ carcinoma, type I stage I endometrial cancer).
6. Patients who underwent surgery for the current relapse with macroscopic complete resection.
7. Prior systemic anticancer therapy within 28 days before randomization.
8. Prior treatment with folate receptor-targeting investigational agents is not allowed.
9. Patients with > Grade 1 peripheral neuropathy.
10. Serious concurrent illness or clinically-relevant active infection.
11. Previous clinical diagnosis of non-infectious interstitial lung disease, including non-infectious pneumonitis.
12. Active or chronic corneal disorders such as Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, 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. Active or chronic corneal disorder.
13. Required use of folate-containing supplements (e.g. folate deficiency).
14. Women of childbearing potential (WOCBP) not protected by highly effective contraceptive methods.
15. Pregnant and/or breast-feeding women.
16. Known hypersensitivity to one of the chemotherapy regimes and/or PARP Inhibitors and/or any of their excipients.
17. Patients with prior hypersensitivity to monoclonal antibodies.
18. Patients with potential risks according to contraindication, warnings or interactions of the used chemotherapeutic agents as stated in the SmPCs are not eligible for participation in this trial.
19. Patients with untreated or symptomatic central nervous system (CNS) metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier.

Secondary endpoints 8

1. Overall survival (OS), defined as the time from randomization to death from any cause.
2. Objective Response Rate (ORR)
3. Efficacy regarding PFS, OS and ORR depending on histologic subtype.
4. Time to serological progressive disease according to GCIG criteria.
5. Time to first subsequent treatment (TFST)
6. Time to second subsequent treatment (TSST)
7. Patient-reported outcomes: Quality of Life (EORTC C-30, OV28)
8. Safety and tolerability of the used drugs evaluated by NCI CTCAE v5.0, records of dose reductions, delays, or interruptions.

Investigational products

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

Test 1

Comparator 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AGO Research GmbH

Sponsor organisation

AGO Research GmbH

Address

Kaiser-Friedrich-Ring 71

City

Wiesbaden

Postcode

65185

Country

Germany

Scientific contact point

Organisation

AGO Research GmbH

Contact name

AGO Study Office

Public contact point

Organisation

AGO Research GmbH

Contact name

AGO Study Office

Third parties 7

Locations

1 EU/EEA country · 15 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 19 files

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

Application history

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