First in Human Study of IMGN151 in Recurrent Gynaecological Cancers

Inclusion Criteria:

1. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

2. Dose-Escalation Phase: Recurrent endometrial cancer or high-grade serous epithelialovarian, fallopian tube, and primary peritoneal cancer (EOC) and who have exhaustedappropriate standard-of-care therapy.

3. Dose Optimization: Platinum-resistant, high-grade serous EOC (PROC) with no previousfolate receptor alpha (FRα)-directed therapy. Participants with PROC will have hadno more than 5 prior lines of therapy, with no more than 2 prior therapies sincedevelopment of platinum resistance.

4. Expansion Phase:

5. For Cohort A, recurrent endometrial cancer (high-grade endometrioid or seroushistology only) with 1-3 prior lines of therapy.

6. For Cohort B, PROC with no previous FRα-directed therapy and no more than 5prior lines of therapy, with no more than 2 prior therapies since developmentof platinum resistance.

7. For Cohort C, PROC with previous FRα-directed therapy with at least oneintervening anticancer therapy between prior FRα-directed therapy and IMGN151.

8. For Cohort D, EOC of one of the following histologies: carcinosarcoma,endometrioid, and low-grade serous carcinoma and have exhausted appropriatestandard-of-care therapy.

9. For Cohort E, cervical cancer including the following histologies: squamouscell carcinoma, adenocarcinoma, adenosquamous carcinoma with 1-4 prior lines oftherapy.

10. For participants with cervical cancer with Combined Positive Score (CPS) > 1 orwith endometrial cancer, prior checkpoint inhibitor therapy, alone or incombination, is required if available locally and medically appropriate.

11. Evaluable lesions

12. Dose-Escalation Phase: Participants may have radiologically evaluable ornonevaluable disease.

13. Dose Optimization and Expansion Phase: Participants must have at least 1 lesionthat meets the definition of measurable disease by RECIST v1.1 (radiologicallymeasured by the investigator).

14. Willing to provide an archival tumor tissue block or slides or to undergo aprocedure to obtain a new biopsy using a low-risk, medically routine procedure.

15. Participants must have stabilized or recovered (Grade 1 or baseline) from all priortherapy-related toxicities (except alopecia or hemoglobin within 10 days beforeCycle 1 Day 1).

16. Participants must have completed any major surgery at least 4 weeks prior to firstdose of IMGN151 and have recovered or stabilized from the side effects of priorsurgery prior to first dose of IMGN151.

17. Participants must have adequate organ and bone marrow function.

Exclusion Criteria:

1. Participants with ovarian cancer with histologies including clear cell, mucinous, orborderline ovarian tumor.

2. With the exception of participants enrolled in Cohort D, participants withovarian cancer with histologies including endometrioid, sarcomatous histology,mixed tumors containing any of the above histologies, as well as low-gradeserous carcinoma.

3. For Cohort A, participants with endometrial cancer with histologies other thanhigh-grade serous or high-grade endometrioid.

4. For Cohort E, participants with cervical cancer with histologies other thanadenocarcinoma, squamous cell carcinoma, and adenosquamous carcinoma.

5. For Cohort B and Dose Optimization: participants with primary platinum refractoryovarian cancer, defined as disease progression on or within 3 months completion offirst platinum-based treatment.

6. Radiation therapy of > 20% of the potential bone marrow

7. Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteriafor Adverse Events (CTCAE) v5.0

8. Participants with the following ocular history and/or concurrent disorders:

9. Active or chronic corneal epithelial disorders other than non-confluentsuperficial keratopathy/keratitis, including confluent superficial punctatekeratopathy/keratitis (SPK) not expected to resolve to non-confluence or betterwithin the screening window with standard-of-care intervention

10. History of corneal transplantation

11. Undergoing active postoperative management for refractive surgery, cataractsurgery, corneal cross-linking, or corneal complications of surgery

12. Active or chronic clinically significant (≥ Grade 3) corneal disorders (forexample, Fuch's dystrophy or neurotrophic keratitis)

13. Active ocular conditions requiring ongoing treatment/monitoring, such asglaucoma, which is not adequately controlled with medication or surgery, wetage-related macular degeneration requiring intravitreal injections, activediabetic retinopathy with macular edema, presence of papilledema, an ocularcondition with high risk of retinal detachment

14. Monocular vision with visual acuity in the worse-seeing eye (worse than 20/200or visual fields less than 20 degrees)

15. Serious concurrent illness or clinically relevant active infection.

16. A history of multiple sclerosis or other demyelinating disease and/or Lambert-Eatonsyndrome (paraneoplastic syndrome)

17. Participants with clinically significant cardiac disease.

18. A history of hemorrhagic or ischemic stroke within 6 months before enrollment

19. A history of cirrhotic liver disease (Child-Pugh Class B or C)

20. Participants with evidence of pneumonitis on baseline imaging or Participants with aprevious clinical diagnosis of noninfectious interstitial lung disease (ILD),including noninfectious pneumonitis

21. Participants with prior hypersensitivity to monoclonal antibodies (mAb)

22. Females who are pregnant or breastfeeding

23. For Dose Optimization and Expansion Phase: Participants who received a priorFRα-targeting agent, with the exception of participants enrolled in the priorFRα-targeting agent, ovarian cancer cohort (Cohort C).

24. Untreated or symptomatic central nervous system metastases

25. A history of other malignancy within 3 years before enrollment