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

Inclusion Criteria: * 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 * 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 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. * 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