Clinical Trials /

Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer

NCT04274426

Description:

This is a multi-center, randomized, two-arm, open-label, comparative phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Ovarian Carcinosarcoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer
  • Official Title: A Randomized Phase II Trial of Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer Eligible for Platinum-based Chemotherapy.

Clinical Trial IDs

  • ORG STUDY ID: AGO-OVAR 2.34
  • SECONDARY ID: 2018-004207-39
  • NCT ID: NCT04274426

Conditions

  • Recurrent Epithelial Ovarian, Fallopian or Peritoneal Carcinoma

Interventions

DrugSynonymsArms
CarboplatinCarboplatin + Mirvetuximab soravtansine (IMGN853)
Pegylated liposomal doxorubicin (PLD)Control arm with Platinum-based chemotherapy
GemcitabineControl arm with Platinum-based chemotherapy
PaclitaxelControl arm with Platinum-based chemotherapy
Mirvetuximab SoravtansineCarboplatin + Mirvetuximab soravtansine (IMGN853)

Purpose

This is a multi-center, randomized, two-arm, open-label, comparative phase II trial of Mirvetuximab soravtansine (IMGN853), in folate receptor alpha (FRα) high recurrent ovarian cancer eligible for platinum-based chemotherapy.

Detailed Description

      136 patients will be randomized into the follow-ing two treatment arms as specified below:

      Arm A: Control arm Platinum-based chemotherapy Arm B: Carboplatin + Mirvetuximab soravtansine
      (IMGN853)
    

Trial Arms

NameTypeDescriptionInterventions
Control arm with Platinum-based chemotherapyActive ComparatorCarboplatin (AUC5, d1) as monotherapy q21d Carboplatin (AUC5, d1) combined with pegylated liposomal doxorubicin (PLD) (30 mg/m², d1) q28d Carboplatin (AUC4, d1) combined with gemcitabine (1000 mg/m2, d1 & d8) q21d Carboplatin (AUC5, d1) combined with paclitaxel (175 mg/m², d1) q21d
  • Carboplatin
  • Pegylated liposomal doxorubicin (PLD)
  • Gemcitabine
  • Paclitaxel
Carboplatin + Mirvetuximab soravtansine (IMGN853)ExperimentalCarboplatin (AUC5, d1) + Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV d1 x 6 cycles q21d, followed by subsequent monotherapy of Mirvetuximab soravtansine (IMGN853) 6 mg/kg IV q3w until disease progression.
  • Carboplatin
  • Mirvetuximab Soravtansine

Eligibility Criteria

        Inclusion Criteria:

          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
             should have included platinum 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:

               1. Hemoglobin ≥ 10.0 g/dL.

               2. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

               3. Platelet count ≥ 100 x 109/L.

               4. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN).

               5. 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.

               6. 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. For 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 use a highly effective method of
             contraception. Such methods include:

               1. Combined (estrogen and progestogen containing) hormonal contraception associated
                  with inhibition of ovulation:

                    -  oral

                    -  intravaginal

                    -  transdermal

               2. Progestogen-only hormonal contraception associated with inhibition of ovula-tion:

                    -  oral

                    -  injectable

                    -  implantable

               3. Intrauterine device (IUD)

               4. Intrauterine hormone-releasing system (IUS)

               5. Bilateral tubal occlusion

               6. Vasectomized partner

               7. Sexual abstinence

        Exclusion Criteria:

          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 on-going 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 Carboplatin.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival (PFS) defined as the time from randomization to progressive disease (PD) or death, whichever occurs earlier. PD is based on investigator assess-ment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Time Frame:Up to 2.5 years. From date of randomization until date of progressive disease (PD) or death, whichever occurs earlier.
Safety Issue:
Description:PD is based on investigator assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Secondary Outcome Measures

Measure:OS
Time Frame:Up to 2.5 years. From date of randomization until date of death from any cause.
Safety Issue:
Description:Overall survival
Measure:ORR
Time Frame:Up to 2.5 years. From date of randomization to date of death death from any cause.
Safety Issue:
Description:Objective response rate
Measure:Efficacy regarding PFS
Time Frame:Up to 2.5 years. From date of randomization to date of death from any cause.
Safety Issue:
Description:Efficacy regarding Progression Free Survival depending on histologic subtype
Measure:Efficacy regarding OS
Time Frame:Up to 2.5 years. From date of randomization to date of death from any cause.
Safety Issue:
Description:Efficacy regarding Overall Survival depending on histologic subtype
Measure:Efficacy regarding ORR
Time Frame:Up to 2.5 years. From date of randomization to date of death from any cause.
Safety Issue:
Description:Efficacy regarding Objective Response Rate depending on histologic subtype
Measure:Serological progressive disease
Time Frame:Up to 2.5 years. From date of randomization to date of death death from any cause.
Safety Issue:
Description:Time to serological progressive disease according to GCIG criteria
Measure:Time to first subsequent treatment (TFST)
Time Frame:Up to 2.5 years. From date of randomization to date of death from any cause.
Safety Issue:
Description:Time to first subsequent treatment (TFST)
Measure:Time to second subsequent treatment (TSST)
Time Frame:Up to 2.5 years. From date of randomization until date of death from any cause.
Safety Issue:
Description:Time to second subsequent treatment (TSST)
Measure:Patient-reported outcomes
Time Frame:Up to 2.5 years. From date of randomization until date of death from any cause.
Safety Issue:
Description:Quality of Life (EORTC C-30)
Measure:Patient-reported outcomes
Time Frame:Up to 2.5 years. From date of randomization until date of death from any cause.
Safety Issue:
Description:Quality of Life (EORTC OV28)
Measure:Safety and tolerability
Time Frame:Up to 2.5 years. From date of randomization until date of death from any cause through study completion.
Safety Issue:
Description:Safety and tolerability of the used drugs evaluated by NCI CTCAE v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AGO Research GmbH

Last Updated

February 17, 2020