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

NCT03835819 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-602
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

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

Conditions

Endometrial Cancer

Keywords

Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  The objective response rate was determined by the frequency of patients who had objective tumor response, determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI, where objective response represents either a confirmed complete response (CR; disappearance of all target lesions) or a confirmed partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters); objective response = CR + PR. The ORR is therefore reported as the percentage of participants who achieved a CR or PR per RECIST v1.1.

  6 months

• Progression-Free Survival at 6 Months (PFS6)

  Progression-free survival at 6 months was determined by the frequency of patients who survived progression-free for at least 6 months after initiating study treatment by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), where disease progression represents at least a 20% increase in the sum of diameters of target lesions, appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.

  6 months

Secondary Outcomes (3)

• Progression-free Survival

  Interval from start of treatment to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first.

• Overall Survival

  Participants are followed for survival status from registration through up to 3 years after removal from study intervention

• Duration of Response

  Interval from best overall response to documented disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurs first.

Study Arms (1)

IMGN853 + Pembrolizumab

EXPERIMENTAL

* Pembrolizumab is administered intravenously once every 3 weeks * IMGN853 is administered intravenously once every 3 weeks

Drug: Pembrolizumab; Drug: IMGN853

Interventions

Pembrolizumab DRUG

Pembrolizumab is an immunotherapy that activates a patient's own immune system to recognize and kill tumor cells

Also known as: Keytruda

IMGN853 + Pembrolizumab

IMGN853 DRUG

Mirvetuximab soravtansine is an antibody-drug conjugate.

Also known as: Mirvetuximab soravtansine, Elahere

IMGN853 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have advanced or recurrent serous endometrial cancer. Patients with mixed histologies/tumors are eligible if the serous component is the dominant histological subtype. 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 three lines of chemotherapy for endometrial carcinoma.
• 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.
• Prior IO therapy targeted to the PD-1/PD-L1 pathway is allowed in up to 19 patients of the total cohort.
• Patients must NOT have received prior therapy with any folate receptor ortholog agents.
• 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

You may not qualify if:

• Participants who have had chemotherapy within 5 half-lives or 4 weeks (whichever is shorter) or radiotherapy within 2 weeks prior to entering the study. Patients completing wide-field radiotherapy (e.g. \>30% of marrow-bearing bones) must not have had treatment within 4 weeks prior to entering study. Participants must have recovered from all AEs due to previous therapy to Grade 1 ≤ or baseline, except alopecia. Participants with endocrine-related AEs who are adequately treated with hormone replacement are eligible.
• Participants who are receiving any other investigational agents.
• Participants with prior exposure to IO agents targeting the PD-1/PD-L1 pathway who discontinued therapy due to treatment-related toxicity deemed to be specifically related to IO therapy.
• 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.
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• ImmunoGen, Inc.: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01605, United States

Location

Northwell Cancer Institute

Lake Success, New York, 11042, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab; mirvetuximab soravtansine

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Dr. Panagiotis Konstantinopoulos
• Organization: Dana-Farber Cancer Institute

Panagiotis_Konstantinopoulos@dfci.harvard.edu

617-632-5269

Study Officials

• Rebecca Porter, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 11, 2019
• Study Start: January 2, 2020
• Primary Completion: June 4, 2024
• Study Completion (Estimated): May 1, 2027
• Last Updated: May 15, 2025
• Results First Posted: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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

Locations

US (3)