A Study of TAK-853 in Adult Participants With Folate Receptor Alpha-Positive Advanced Ovarian Cancer And Other Solid Tumors

Inclusion Criteria:

Phase 1 part:

1. Diagnosis, allowable prior therapy, and disease measurability requirements:

2. All participants must have a pathologically documented, following advancedsolid tumor known to express folate receptor alpha (FR alpha), that isresistant or refractory to standard treatment, for which no standard treatmentis available, or the participant refuses standard therapy.

• Ovarian cancer
• Endometrial cancer
• Non-small cell lung cancer (NSCLC)
• Triple-negative breast cancer (TNBC)
• Cholangiocarcinoma
• Colorectal cancer (CRC)
• Gastro-esophageal adenocarcinoma Note: Participants with a solid tumortype other than the above will be eligible as long as there is priordocumentation of tumor FR alpha expression.

2. All participants without prior documentation of tumor FR alpha expression byimmunohistochemistry (IHC) must be willing to provide an archival tumor tissueblock or slides, or undergo procedure to obtain a new biopsy using a low risk,medically routine procedure for IHC confirmation of FR alpha positivity of >=1%of viable tumor cells with membrane staining at >=1+ intensity for entry intoPhase 1 part

3. There is no upper limit on the number of prior cytotoxic or targeted therapiesthe participant may have received. Participants may have received priortreatment with investigational compounds targeting folate receptor excludingMIRV.

4. Participants must have measurable or non-measurable disease (such as largeabdominal masses that cannot be accurately measured) according to ResponseEvaluation Criteria in Solid Tumors (RECIST) 1.1.

5. Participant must have an Eastern Cooperative Oncology Group Performance Status (ECOGPS) of 0 or 1

6. Time from Prior Therapy:

• Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever isshorter (6 weeks for prior nitrosoureas or mitomycin C)

• FR alpha-targeted therapy: five half-lives or four weeks, whichever is longer

• Radiotherapy: wide-field radiotherapy (e.g. affecting at least 30% of the bonemarrow) completed at least four weeks, or focal radiation completed at leasttwo weeks, prior to starting study drug

4. Participants must have stabilized or recovered (Grade 1 or baseline) from all priortherapy-related toxicities

5. Major surgery must be completed four weeks prior to first dose of TAK-853.Participants must have recovered or stabilized from the side effects prior to studytreatment.

6. Participants must have adequate hematologic, liver and kidney function as defined bythe following parameters:

7. Absolute neutrophil count (ANC) >= 1.5*10^9/L (1,500/microliter) withoutgranulocyte colony stimulating factor (G-CSF) in the prior 10 days orlong-acting white blood cell (WBC) growth factors in the prior 20 days

8. Platelet count >= 100.0*10^9/L (100,000/microliter; without platelettransfusion in the prior 10 days)

9. Hemoglobin >= 9.0 g/dL without packed red blood cell (PRBC) transfusion in theprior 21 days

10. Serum creatinine =< 1.5* upper limit of normal (ULN) or estimated creatinineclearance of >= 30 mL/minute (as calculated using the Cockcroft Gaultequation),

11. Aspartate aminotransferase (AST) =< 2.5* ULN; alanine aminotransferase (ALT) =< 2.5* ULN (AST, ALT < 5* ULN if liver metastases), and

12. Total bilirubin =< 1.5* ULN (participants with documented diagnosis of Gilbertsyndrome are eligible if total bilirubin < 3.0* ULN)

13. Participants with central nervous system (CNS) disease involvement are eligible ifthey have had brain metastases resected or have received radiation therapy ending atleast 4 weeks prior to study Day 1 and they meet all of the following criteria:

14. Residual neurological symptoms =< Grade 1

15. No dexamethasone requirement, and

16. Follow-up MRI shows no progression of treated lesions and no new lesions appearing.

Phase 2 part:

1. Participants must have a confirmed diagnosis of high-grade serous epithelial ovariancancer, primary peritoneal cancer, or fallopian tube cancer

2. Participants must have platinum-resistant disease:

3. Participants who have only had 1 line of platinum-based therapy must havereceived at least 4 cycles of platinum, must have had a response (completeresponse [CR] or partial response [PR]) and then progressed between > 3 monthsand =< 6 months after the last dose date of platinum

4. Participants who have received 2 or 3 lines of platinum therapy must haveprogressed on or within 6 months after the date of the last dose of platinumNote: Progression should be calculated from the date of the last administereddose of platinum therapy to the date of the radiographic imaging showingprogression Note: Participants who are primary platinum-refractory duringfront-line treatment are excluded (see exclusion criteria)

5. Participants must have progressed radiographically on or after their most recentline of therapy

6. Participants must be willing to provide an archival tumor tissue block or slides, orundergo procedure to obtain a new biopsy using a low risk, medically routineprocedure for IHC confirmation of FR alpha expression (reported as "positive") asdefined by the Ventana FOLR1 Assay. Tumors must be confirmed FR alpha-high asdefined by FR alpha positivity of >=75% of viable tumor cells with membrane stainingat >=2+ intensity for entry into the Phase 2.

7. Participants must have at least one lesion that meets the definition of measurabledisease by RECIST v1.1 criteria (radiologically measured by the Investigator).

8. Participants must have received at least 1 but no more than 3 prior systemic linesof anticancer therapy, and for whom single-agent therapy is appropriate as the nextline of treatment: a. Neoadjuvant +- adjuvant considered one line of therapy b. Maintenance therapy (e.g., bevacizumab, poly-ADP ribose polymerase [PARP] inhibitors) will be consideredas part of the preceding line of therapy (i.e., not counted independently) c.Therapy changed due to toxicity in the absence of progression will be considered aspart of the same line (i.e., not counted independently) d. Hormonal therapy will becounted as a separate line of therapy unless it was given as maintenance

9. Participant must have an ECOG PS of 0 or 1

10. Time from prior therapy:

11. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)

12. Focal radiation completed at least 2 weeks prior to first dose of study drug

13. Participants must have stabilized or recovered (Grade 1 or baseline) from all priortherapy-related toxicities

14. Major surgery must be completed at least 4 weeks prior to first dose and theparticipant must have recovered or stabilized from the side effects of prior surgery

15. Participants must have adequate hematologic, liver, and kidney functions defined as:

16. ANC >= 1.5* 10^9/L (1,500/microliter) without G-CSF in the prior 10 days orlong-acting WBC growth factors in the prior 20 days

17. Platelet count >= 100* 10^9/L (100,000/microliter) without platelet transfusionin the prior 10 days

18. Hemoglobin >= 9.0 g/dL without PRBC transfusion in the prior 21 days

19. Serum creatinine =< 1.5* ULN or estimated creatinine clearance of >= 30mL/minute (as calculated using the Cockcroft Gault equation).

20. AST and ALT =< 3.0* ULN

21. Total bilirubin =< 1.5* ULN (participants with documented diagnosis of Gilbertsyndrome are eligible if total bilirubin < 3.0* ULN)

22. Serum albumin >= 2 g/dL

Exclusion Criteria:

Phase 1 part:

1. Participant with > Grade 1 peripheral neuropathy per National Cancer InstituteCommon Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

2. Participants with active or chronic corneal disorders, history of cornealtransplantation, or active ocular conditions requiring ongoing treatment/monitoringsuch as uncontrolled glaucoma, wet age-related macular degeneration requiringintravitreal injections, active diabetic retinopathy with macular edema, maculardegeneration, presence of papilledema, and/or monocular vision.

3. Serious concurrent illness, including, but not limited to the following:

4. Clinically relevant active infection including - Active hepatitis B or Cinfection (whether or not on active antiviral therapy)

• Human Immunodeficiency Virus (HIV) infection
• Active cytomegalovirus infection
• Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is notmandatory for study entry, testing should follow local clinical practiceguidelines and standards
• Any other known concurrent infectious disease requiring IV antibioticswithin 2 weeks before starting study drug Note: Testing at screening forhepatitis is required, while not required for the remaining infectionsabove unless clinically indicated. Participants with known hepatitis Bsurface antigen seropositivity and/or detectable hepatitis C virus RNAwill be excluded. Participants who have positive hepatitis B core antibodyand/or hepatitis B surface antibody can be enrolled but must have anundetectable serum hepatitis B virus DNA. Participants who have positivehepatitis C virus antibody must have an undetectable hepatitis C virus RNAserum level. Participants will be monitored and managed according toGuideline for the prevention of immunosuppressive therapy orchemotherapy-induced reactivation of hepatitis B virus infection (TheJapan Society of Hepatology 2022).

2. Participants with clinically significant cardiac disease including, but notlimited to, any one of the following:

• Myocardial infarction =< 6 months prior to first dose of study medication
• Unstable angina pectoris
• Uncontrolled congestive heart failure (New York Heart Association > classII)
• Uncontrolled >= Grade 3 hypertension (per NCI CTCAE v5.0)
• Uncontrolled cardiac arrhythmias
• Severe aortic stenosis
• >= Grade 3 cardiac toxicity following prior chemotherapy

3. History of multiple sclerosis or other demyelinating disease, Lambert-Eatonsyndrome (paraneoplastic syndrome), history of hemorrhagic or ischemic strokewithin the last six months, or alcoholic liver disease.

4. Previous clinical diagnosis of interstitial lung disease (ILD), includingpneumonitis.

5. Any other concomitant anti-cancer treatment such as immunotherapy, biotherapy,radiotherapy, chemotherapy, investigative therapy, or high-dose steroids; however,low-dose steroids and Luteinizing Hormone Releasing Hormone (LHRH) at doses thathave been stable for >= 14 days are permitted for participants with prostate cancer

6. Known hypersensitivity to previous monoclonal antibody therapy or maytansinoids, orstudy drugs and/or any of their excipients

7. Prior history of solid tumor malignancy within the last 3 years except foradequately treated basal cell or squamous cell skin cancer, in situ cervical cancer,in situ breast cancer, in situ prostate cancer (participants must have shown noevidence of active disease for 2 years prior to enrollment)

8. Participants with required use of folate-containing supplements (e.g., folatedeficiency)

9. Participants who have received prior allogeneic or autologous bone marrowtransplants

Phase 2 part:

1. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology,mixed tumors containing any of the above histologies, or low-grade or borderlineovarian tumor

2. Participants with primary platinum-refractory disease, defined as disease that didnot respond to (CR or PR) or has progressed within 3 months of the last dose offirst line platinum-containing chemotherapy

3. Participants with prior wide-field radiotherapy affecting at least 20% of the bonemarrow

4. Participants with > Grade 1 peripheral neuropathy per NCI CTCAE v5.0

5. Participants with active or chronic corneal disorders, history of cornealtransplantation, or active ocular conditions requiring ongoing treatment/monitoringsuch as uncontrolled glaucoma, wet age-related macular degeneration requiringintravitreal injections, active diabetic retinopathy with macular edema, maculardegeneration, presence of papilledema, and/or monocular vision

6. Participants with serious concurrent illness or clinically relevant activeinfection, including, but not limited to the following:

7. Active hepatitis B or C infection (whether or not on active antiviral therapy)

8. HIV infection

9. Active cytomegalovirus infection

10. Active COVID-19/SARS-CoV-2 infection. Although SARS-CoV-2 testing is notmandatory for study entry, testing should follow local clinical practiceguidelines and standards.

11. Any other concurrent infectious disease requiring IV antibiotics within 2 weeksbefore starting study drug Note: Testing at screening for hepatitis (a) isrequired, while not required for the remaining infections above (b-e) unlessclinically indicated.

Participants with known hepatitis B surface antigen seropositivity and/or detectable hepatitis C virus RNA will be excluded. Participants who have positive hepatitis B core antibody and/or hepatitis B surface antibody can be enrolled but must have an undetectable serum hepatitis B virus DNA.

Participants who have positive hepatitis C virus antibody must have an undetectable hepatitis C virus RNA serum level. Participants will be monitored and managed according to Guideline for the prevention of immunosuppressive therapy or chemotherapy-induced reactivation of hepatitis B virus infection (The Japan Society of Hepatology 2022).

7. Participants with history of multiple sclerosis or other demyelinating diseaseand/or Lambert-Eaton syndrome (paraneoplastic syndrome) 8. Participants withclinically significant cardiac disease including, but not limited to, any one of thefollowing:

8. Myocardial infarction =< 6 months prior to first dose of study medication

9. Unstable angina pectoris

10. Uncontrolled congestive heart failure (New York Heart Association > class II)

11. Uncontrolled >= Grade 3 hypertension (per NCI CTCAE v5.0)

12. Uncontrolled cardiac arrhythmias 9. Participants with a history of hemorrhagic orischemic stroke within six months prior to first dose of TAK-853 10. Participantswith a history of cirrhotic liver disease (Child-Pugh Class B or C) 11. Participantswith a previous clinical diagnosis of ILD, including pneumonitis 12. Participantswith required use of folate-containing supplements (e.g., folate deficiency) 13.Participants with prior hypersensitivity to monoclonal antibodies or maytansinoids

13. Participants with prior treatment with TAK-853 or other FR alpha-targetingagents 15. Participants with untreated or symptomatic CNS metastases 16.Participants with a history of other malignancy within 3 years prior to first doseof TAK-853 Note: does not include tumors with a negligible risk for metastasis ordeath (e.g., adequately controlled basal-cell carcinoma or squamous-cell carcinomaof the skin, or carcinoma in situ of the cervix or breast) 17. Prior knownhypersensitivity reactions to study drugs and/or any of their excipients