Participants must meet all the following inclusion criteria to be enrolled in the study:
1. Written informed consent is obtained prior to any procedures that are not considered standard of care.

2. ≥18 years of age.

3. In Part 1: a. Participants with histologically or cytologically confirmed advanced solid tumors, who have failed or are ineligible for standard of care therapies. b. Have progressed on at least one prior systematic anti-tumor regimen, and presence of at least one measurable or evaluable tumor lesion according to RECIST Version 1.1 (Section 13.4.1). Measurable lesions are required in the backfill period. c. In the backfill period, eligible tumor types are limited to high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, USC, clear cell RCC, papillary RCC and adenocarcinoma of NSCLC without actionable mutation of epidermal growth factor receptor (EGFR). For participants with NSCLC, presence of CDH6 expression through immunohistochemical examination of tumor tissue by central laboratory is required.

4. In Part 2: Participants must have a diagnosis of specific type of metastatic or locally advanced solid tumors and have progressed on or cannot benefit from the most recent systematic anti-tumor regimen (unless otherwise specified), with presence of at least one measurable lesion according to RECIST Version 1.1 (Section 13.4.1). 

Platinum-resistant ovarian cancer cohort:
a. Participants with histologically or cytologically confirmed high-grade serous ovarian cancer, high-grade endometrioid ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
b. Have platinum-resistant disease, defined as: Participants who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a best response of not progressive disease (PD), and then progressed between >90 days and ≤180 days after the date of the last dose of platinum; Participants who have received ≥ 2 lines of platinum therapy must have progressed ≤180 days after the date of the last dose of platinum. Note: Time interval of progression should be calculated from the date of the last administered dose of platinum therapy to the date of progression. 

Renal cell carcinoma cohort:
a. Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.
b. For clear cell RCC: Participants who have progressed on or after systemic treatment including a PD-1/PD-L1 checkpoint inhibitor and a VEGF-TKI, either given concurrently or in separate lines of therapy.
c. For papillary RCC: Participants without any prior systemic treatment is acceptable.

Uterine serous carcinoma cohort:
a. Participants with histologically- or cytologically-confirmed USC.  
b. Have progressed on or after systemic treatment that contained platinum-based chemotherapy. 

Non-Small Cell Lung Cancer cohort:
a. Participants with histologically- or cytologically-confirmed adenocarcinoma of NSCLC, and without actionable mutation of epidermal growth factor receptor (EGFR)
b. Presence of CDH6 expression through immunohistochemical examination of tumor tissue.
c. For participants with no actionable mutations: Have progressed on or after systemic treatment including anti-PD-1/PD-L1 antibody and platinum-based chemotherapy, either given concurrently or in separate lines of therapy. Progression within 6 months after completion of adjuvant therapy is considered failure of first-line therapy.
d. For participants with actionable mutations other than EGFR: Have failed at least one established standard anti-cancer targeted therapy, anti-PD-1/PD-L1 antibody and platinum-based chemotherapy (PD-1/PD-L1 and chemotherapy either given concurrently or in separate lines of therapy) or in the opinion of the Investigator have been considered ineligible for a particular form of standard of care therapy on medical grounds.

5. ECOG performance status score of 0 or 1 (Section 13.4.2).

6. Life expectancy of ≥12 weeks.

7. Have adequate organ function as indicated by the following laboratory values. Whole blood transfusion, blood component transfusion or colony-stimulating factors (e.g., GCSF, GM-CSF or recombinant erythropoietin) within 2 weeks prior to the laboratory tests are not allowed: 

Hematological:
c. ANC ≥1.5 × 109/L. 
d. Platelets ≥100 × 109/L.
e. Hemoglobin ≥90 g/L. Hepatic:
f. ALT and AST ≤2.5 × ULN, or ALT and AST ≤5.0 × ULN with liver metastasis.
g. Serum T-BIL ≤1.5 × ULN.
h. Serum albumin ≥ 30 g/L Renal:
i. Cr clearance ≥60.0 mL/min (calculated according to the Cockcroft-Gault formula). Coagulation:
j. Coagulation: INR ≤1.5 or prothrombin time ≤1.5 × ULN (for participant receiving anticoagulant therapy, the PT or INR must be within the therapeutic range of intended use for the anticoagulant). Cardiac:
k. LVEF >50%. 

8. WOCBP (Section 13.1.1) must have a negative serum pregnancy test within 72 hours prior to the start of study treatment. WOCBP or male participants are required to use highly effective contraceptive methods (Section 13.1.2), and agree to refrain from donating sperm/egg from signing of main informed consent through 180 days after the last dose of study treatment.

9. Able to provide tumor tissue sample (archival or newly obtained core or excisional biopsy) at biomarker-screening (for NSCLC in both Part 1 and 2) or screening (for nonNSCLC in Part 1) visit of a tumor lesion not previously irradiated for CDH6 testing. Note: Archival tissue should be obtained within 5 years of the date of informed consent. For Part 2: Willing to undergo fresh tumor biopsy at screening visit from a lesion that can be biopsied at an acceptable clinical risk as judged by the investigator. Note: If archival tissue is available from a prior biopsy performed ≤6 months of informed consent, the fresh biopsy may be waived.. 

A participant meeting any of the following criteria is not eligible to participate in this study:

Target Disease Exceptions

1. For Part 2: has clear cell, mucinous or sarcomatous histology, mixed tumors containing any histology, or low-grade/borderline ovarian cancer; mixed non-small cell and small cell carcinoma, or adenosquamous cell lung cancer with an adenocarcinoma component <50% (the participant is eligible if the adenocarcinoma component is ≥50%).

2. Any other malignancy within 2 years prior to the first dose of the study treatment except for localized cancers that are considered to have been cured and in the opinion of the Investigator present a low risk for recurrence. Examples include basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.

Medical Conditions

3. Participant has symptomatic central nervous system (CNS) metastases, or CNS metastases requiring CNS-directed local therapy (such as radiotherapy or surgery) or corticosteroids therapy within 2 weeks of first dose of study treatment.

4. History of bowel obstruction within 3 months prior to the first dose of study treatment.

5. Known psychiatric disorder or drug abuse that would interfere the study requirements.

6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring drainage or medical intervention within 4 weeks before the first dose of study treatment.

7. Any active infection requires systemic treatment via intravenous infusion within 2 weeks prior to the first dose of study treatment.

8. History of non-infectious pneumonitis that has required a course of oral or intravenous steroids to assist with recovery, or ILD or severe obstructive pulmonary disease. Prior/Concomitant Therapy

9. Prior exposure to other CDH6-targeted agents or an ADC with a topoisomerase I inhibitor payload (e.g., raludotatug deruxtecan/DS-6000).

10. Has not recovered (i.e., to CTCAE version5.0 Grade 1 or to baseline) from previous anticancer therapy-induced AEs. Note: Grade ≤2 AEs with no impact on participant safety are exceptions to this criterion and may qualify for the study, e.g., Grade ≤2 hair loss and neuropathy caused by chemotherapy.

11. Is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of first dose of SIM0505. Note: This does not include participation in the follow-up phase of a study.

12. Major surgery within 2 weeks of receiving the first dose of study treatment (minor procedures such as mediastinoscopy, insertion of a central venous access device, insertion of a feeding tube, needle biopsy and percutaneous nephrostomy are not considered major surgery). 

13. Has received prior anti-cancer therapies within the following time frames prior to the first dose of study treatment:

a.  Previous cytotoxic therapy, anticancer targeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks.

b.  Anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study treatment.

c.  Chinese medicines/herbal preparations with anticancer indication taken within 2 weeks.

d.  Radiation therapy <4 weeks. 

14. Use of any live vaccine therapy within 4 weeks prior to the first dose of study treatment.  

15. Administration of below medications (Section 13.4.6) ≤14 days prior to the first dose of SIM0505. a.  Strong and moderate CYP3A4 inhibitors b.  Drugs with known risk of TdP 

Concomitant disease/other exclusions

16. Known HIV infection or known AIDS.

17. Active hepatitis B (HBsAg or HBcAb positive, and HBV-DNA ≥2 000 IU/mL or ≥10 000 copies/mL) or hepatitis C (HCV antibody positive and HCV RNA ≥ ULN) infection; participant with HBsAg positive or detectable HBV-DNA at screening should receive antiviral treatment as per local practice during the study

18. Participants with clinically significant cardiovascular diseases, including but not limited to myocardial infarction, severe/unstable angina pectoris, primary cardiomyopathy, cerebrovascular accident (including transient cerebral ischemia, cerebral hemorrhage, cerebral infarction), or congestive heart failure (New York Heart Association class >2, Section 13.4.3) in the past 6 months prior to the first dose of the study treatment; symptomatic coronary heart disease requiring drug treatment; arrhythmia requiring drug treatment; QTcF interval >470 msec; or uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg despite adequate drug treatment).

19. History of allogeneic organ transplantation or graft-versus-host disease.

20. Known hypersensitivity to study drug or any of the excipients.

21. Participant is pregnant or breastfeeding.

22. Other conditions that researchers consider inappropriate for inclusion.