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A Phase 2 Study of Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab in Endometrial Cancer (EC)

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ClinicalTrials.gov Identifier: NCT03835819
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
ImmunoGen, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Panagiotis Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying a drug combination as a possible treatment for endometrial cancer.

The drugs involved in this study are:

  • mirvetuximab soravtansine (IMGN853)
  • pembrolizumab

Condition or disease Intervention/treatment Phase
Endometrial Cancer Drug: Pembrolizumab Drug: IMGN853 Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved mirvetuximab soravtansine as a treatment for any disease.

The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved for other uses.

In this research study, the investigators are studying the combination of mirvetuximab soravtansine and pembrolizumab. Pembrolizumab is an immunotherapy that activates a patient's own immune system to recognize and kill tumor cells. Pembrolizumab by itself may not be enough to kill cancer cells in all people with cancer. In this study, all patients will receive mirvetuximab soravtansine and pembrolizumab. Mirvetuximab soravtansine is an antibody-drug conjugate. That is a type of agent that attaches a chemotherapy drug to a molecule that binds a protein on the outside of cancer cells. The protein targeted by mirvetuximab soravtansine is called folate receptor-alpha (FRα). FRα is expressed on the surface of certain cancers, including endometrial cancer cells. Mirvetuximab soravtansine is expected to kill cancer cells by delivering chemotherapy to cells that have high levels of FRα. To participate in this study, a sample of your tumor was previously tested, and was found to have high levels of FRα. Mirvetuximab soravtansine also may also active immune cells and improve the response to immunotherapies like pembrolizumab.

In this study, the investigators expect to learn whether the combination of pembrolizumab and mirvetuximab soravtansine can shrink endometrial cancers or prevent their growth for at least 6 months. The investigators will also learn more about the side effects patients experience who receive this treatment. The investigators also plan to learn more about which patients are likely to benefit from this treatment


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Two-stage, Study of Mirvetuximab Soravtansine (IMGN853) in Combination With Pembrolizumab in Patients With Microsatellite Stable (MSS) Recurrent or Persistent Endometrial Cancer (EC)
Estimated Study Start Date : March 31, 2019
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IMGN853 + Pembrolizumab
  • Pembrolizumab is administered intravenously once every 3 weeks
  • IMGN853 is administered intravenously once every 3 weeks
Drug: Pembrolizumab
Pembrolizumab is an immunotherapy that activates a patient's own immune system to recognize and kill tumor cells

Drug: IMGN853
Mirvetuximab soravtansine is an antibody-drug conjugate.
Other Name: Mirvetuximab soravtansine




Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 6 months ]
  2. Progression Free Survival [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Duration of response [ Time Frame: 2 years ]
  2. Overall Survival [ Time Frame: 2 Years ]
  3. Immune-related progression-free survival [ Time Frame: 2 years ]
  4. Immune-related progression of disease [ Time Frame: 2 Years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have advanced or recurrent serous or endometrioid endometrial cancer. In addition, the tumors must be:
  • microsatellite stable (MSS) as documented by either intact immunohistochemical (IHC) nuclear expression of the mismatch repair genes MSH2, MSH6, MLH1 and PMS2; or microsatelitte stable by polymerase chain reaction (PCR), next generation sequencing, or other CLIA-approved method;

AND

  • FRα positive by central immunohistochemistry (IHC, Section 9.1). If archival tissue does not meet FRα criteria, a fresh biopsy tumor sample may be submitted and used to meet this criterium. If a fresh tumor biopsy cannot be done safely the patient will not be allowed to enroll on this study.

    • Participants must have measurable disease as defined by RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
    • Prior therapy: Patients must have had one, but no more than two lines of chemotherapeutic regimen for management of endometrial carcinoma in the recurrent setting. Patients who have only received chemotherapy in the adjuvant setting will not be eligible for the study.
  • Prior hormonal therapy is allowed (no washout period is required after hormonal therapy) and does not count as a prior line of therapy. Hormonal therapy in combination with CDK4/6 inhibitors or mTOR or other PI3K-pathway inhibitors is allowed and does not count as a line of prior therapy.
  • Patients must NOT have received any class of drugs targeted to the PD-1/PD-L1 pathway or folate receptor orthologs.

    • Age 18 or greater years. Because insufficient dosing or adverse event data are currently available on the use of mirvetuximab soravtansine and pembrolizumab in participants <18 years of age, children are excluded. Endometrial cancer is rare in the pediatric population.
    • ECOG performance status 0 or 1
    • Participants must have normal organ and marrow function as defined below:
  • leukocytes ≥3,000/mcL
  • absolute neutrophil count ≥1,500/mcL
  • platelets ≥100,000/mcL
  • hemoglobin ≥ 9.0 g/dL
  • total bilirubin ≤ 1.5 x institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
  • creatinine ≤ institutional upper limit of normal OR
  • creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.

    -Time from prior therapy:

  • Systemic anti-neoplastic therapy: 5 half-lives or 4 weeks, whichever is shorter. Hormonal therapy is not considered anti-neoplastic therapy.
  • Radiotherapy: wide-field radiotherapy (e.g. > 30% of marrow-bearing bones) completed at least 4 weeks, or focal radiation completed at least 2 weeks, prior to starting study treatment

    • The effects of agents used in this study on the developing human fetus are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during study treatment, and for at least twelve weeks after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
    • Women of child-bearing potential must have a negative serum pregnancy test within 3 days prior to the first dose of study treatment.
    • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Participants who have had chemotherapy within 4 weeks or radiotherapy within 2 weeks prior to entering the study. Participants must have recovered from all AEs due to previous therapy to Grade 1 ≤ or baseline, except alopecia.
  • Participants who are receiving any other investigational agents.
  • Prior exposure to agents targeting the PD-1/PD-L1 pathway.
  • Required use of folate-containing supplements (e.g. folate deficiency).
  • Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to monoclonal antibodies (including antibody drug-conjugates or checkpoint inhibitors).
  • Uncontrolled intercurrent illness including, but not limited to, any of the following within 6 months of first study treatment: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled hypertension (≥ Grade 3), hypertensive crisis or hypertensive encephalopathy, uncontrolled cardiac arrhythmias, thrombotic or ischemic stroke, clinically-significant vascular disease (e.g. aortic aneurysm, or dissecting aneurysm), severe aortic stenosis, clinically significant peripheral vascular disease, or ≥ Grade 3 cardiac toxicity following prior chemotherapy, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Active or chronic corneal disorder, including but not limited to the following: Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, and also active ocular conditions requiring on-going treatment/monitoring such as wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, presence of papilledema, and acquired monocular vision.
  • Serious clinically-relevant active infection, including known HIV infection, varicella-zoster virus, cytomegalovirus infection, has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) or any other known concurrent infectious disease requiring IV antibiotics with within 2 weeks of study enrollment are ineligible because of the potential for immune side effects.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Current or prior use of immunosuppressive medication within 7 days prior to enrollment with the following exceptions to this exclusion criterion:

    • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
    • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, hypo-or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Pregnant or nursing women are excluded from this study because effects of agents used in this study on infants or the developing human fetus are unknown
  • Presence of other malignancies unless they are considered cured by patient's oncologist

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03835819


Contacts
Contact: Panagiotis Konstantinopoulos, MD, PhD 617-632-2334 Panagiotis_Konstantinopoulos@DFCI.HARVARD.EDU

Locations
United States, Massachusetts
Massachusetts General Hospital Cancer Center Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Oladapo O Yeku, MD       oyeku@partners.org   
Principal Investigator: Oladapo O Yeku, MD         
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Meghan Shea, MD       mshea4@bidmc.harvard.edu   
Principal Investigator: Meghan Shea, MD         
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Panagiotis Konstantinopoulos, MD, PhD    617-632-2334    Panagiotis_Konstantinopoulos@DFCI.HARVARD.EDU   
Principal Investigator: Panagiotis Konstantinopoulos, MD, PhD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
ImmunoGen, Inc.
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Panagiotis Konstantinopoulos, MD,PhD Dana-Farber Cancer Institute

Responsible Party: Panagiotis Konstantinopoulos, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03835819     History of Changes
Other Study ID Numbers: 18-602
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Panagiotis Konstantinopoulos, MD, PhD, Dana-Farber Cancer Institute:
Endometrial Cancer

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Pembrolizumab
Maytansine
Immunoconjugates
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs