A study to test Mirvetuximab Soravtansine (IMGN853) aganist doctor's choice of cancer medicines in women with advanced Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Immunogen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Nov 2020 → 30 Oct 2024

Decision date (initial)

2024-10-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ImmunoGen, Inc.

External identifiers

EU CT number

2024-516111-25-00

EudraCT number

2019-003509-80

ClinicalTrials.gov

NCT04209855

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Dose response

To compare the progression-free survival (PFS) of patients randomized to mirvetuximab soravtansine (MIRV) vs. Investigator’s choice of chemotherapy (IC Chemo)

Secondary objectives 7

1. To compare the objective response rate (ORR) of patients randomized to MIRV vs. IC Chemo
2. To compare overall survival (OS) of patients randomized to MIRV vs. IC Chemo
3. To compare the primary patient-reported outcome (PRO) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-OV28 (Abdominal/GI Symptom Scale) assessment from patients randomized to MIRV vs. IC Chemo
4. To compare the safety and tolerability of MIRV vs. IC Chemo
5. To compare the duration of response (DOR) in patients randomized to MIRV vs. IC Chemo
6. To compare the CA-125 response rate (RR) per Gynecologic Cancer Intergroup (GCIG) CA- 125 criteria in patients randomized to MIRV vs. IC Chemo
7. To compare the time to progression or death on the next line of treatment (PFS2) in patients randomized to MIRV vs. IC Chemo

Conditions and MedDRA coding

Platinum-Resistant Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers with High Folate Receptor-Alpha Expression

Study design 1 period

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 16

1. Female patients ≥ 18 years of age
2. Patients must have a confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer
3. Patients must have platinum-resistant disease: a. Patients who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between > 3 months and ≤ 6 months after the date last dose of platinum Patients who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum 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
4. Patients must have progressed radiographically on or after their most recent line of therapy
5. Patients must be 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
6. Patient’s tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
7. Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
8. Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment: a. Adjuvant ± neoadjuvant considered one line of therapy. b. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as 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 as 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
9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
10. Time from prior therapy: a. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter) b. Focal radiation completed at least 2 weeks prior to first dose of study drug
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
12. Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery
13. Patients must have adequate hematologic, liver, and kidney functions defined as: a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days b. Platelet count ≥ 100 x 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 21 days d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN f. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN) g. Serum albumin ≥ 2 g/dL
14. Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) in while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of Pac, PLD, or Topo
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug

Exclusion criteria 21

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 to (CR or PR) or has progressed within 3 months of the last dose of first line platinumcontaining chemotherapy
3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
4. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
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, and /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 before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated
7. Patients with 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 assigned to PLD stratum only: • Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
13. Patients with required use of folate-containing supplements (eg, folate deficiency)
14. Patients with prior hypersensitivity to monoclonal antibodies
15. Women who are pregnant or lactating
16. Patients with prior treatment with MIRV or other FRα-targeting agents
17. Patients with untreated or symptomatic central nervous system (CNS) metastases
18. 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, or carcinoma in situ of the cervix or breast
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
20. 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
21. 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 1

1. PFS, defined as the time from date of randomization until Investigator-assessed progressive disease (PD) or death, whichever occurs first. Results will be summarized by arm − Kaplan-Meier method for survival function estimate − Stratified Cox proportional hazard regression for hazard ratio (HR) estimate − Stratified log-rank test for hypothesis testing

Secondary endpoints 7

1. Objective response includes best response of complete response (CR) or partial response (PR) as assessed by the Investigator − Stratified Cochran-Mantel-Haenszel (CMH) test for treatment comparison − Clopper-Pearson method for 95% CI estimation
2. OS defined as the time from date of randomization until the date of death. Patients alive at the time of analysis will be censored at the last known date known to be alive − Kaplan-Meier method for survival function estimate − Stratified Cox proportional hazard regression for HR estimate − Stratified log-rank test for hypothesis testing
3. Primary PRO assessment, defined as the number of patients achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of EORTC QLQ-OV28
4. DOR defined as the time from initial response until Investigator-assessed PD for all patients who achieve a confirmed objective response (PR or CR) − Kaplan-Meier method for survival function estimate − Unstratified Cox proportional hazard regression for HR estimate − Unstratified log-rank test for hypothesis testing
5. CA-125 response determined using the GCIG criteria defined in the protocol. CA-125 response per GCIG criteria will be determined programmatically
6. PFS2 defined as the time from date of randomization until second disease progression or death whichever occurs first. Results will be summarized by arm
7. TEAEs, laboratory test results, physical examination findings, and vital signs

Investigational products

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

Test 1

Comparator 9

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Immunogen Inc.

Sponsor organisation

Immunogen Inc.

Address

830 Winter Street

City

Waltham

Postcode

02451-1477

Country

United States

Scientific contact point

Organisation

Immunogen Inc.

Contact name

Graham Walker

Public contact point

Organisation

Immunogen Inc.

Contact name

Clinical Trial contact point

Third parties 3

Sponsor responsibilities

Article 77 compliance

Immunogen Inc.

Contact point sponsor

Immunogen Inc.

Article 77 implementation

Immunogen Inc.

Locations

1 EU/EEA country · 16 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 25 files

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

Application history

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