A Phase I Study of SIM0505 in Participants With Advanced Solid Tumors

Inclusion Criteria:

1. Written informed consent is obtained prior to any procedures that are not consideredstandard of care

2. ≥18 years of age.

3. In Part 1:

4. Participants with histologically or cytologically confirmed advanced solidtumors, who have failed or are ineligible for standard of care therapies.

5. Have progressed on at least one prior systematic anti-tumor regimen, andpresence of at least one evaluable lesion according to RECIST Version 1.1.Measurable lesions are required in the backfill period.

6. In the backfill period, eligible tumor types are limited to high-grade serousovarian cancer, high-grade endometrioid ovarian cancer, USC, clear cell RCC,papillary RCC and adenocarcinoma of NSCLC without actionable mutation ofepidermal growth factor receptor (EGFR). For participants with NSCLC, presenceof CDH6 expression through immunohistochemical examination of tumor tissue bycentral laboratory is required.

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

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.

Renal cell carcinoma cohort:

a. Participants with histologically- or cytologically-confirmed clear cell RCC or papillary RCC.

Uterine serous carcinoma cohort:

a. Participants with histologically- or cytologically-confirmed USC.

Non-Small Cell Lung Cancer cohort:

1. Participants with histologically- or cytologically-confirmed adenocarcinoma of NSCLCwithout actionable mutation of EGFR.

2. Presence of CDH6 expression through immunohistochemical examination of tumor tissue.

3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

4. Life expectancy of ≥12 weeks. 7. Have adequate organ function as indicated by thelaboratory values listed within the protocol.

5. Women of childbearing potential (WOCBP)must have a negative serum pregnancy testwithin 72 hours prior to the start of study treatment. WOCBP or male participantsare required to use highly effective contraceptive methods , and agree to refrainfrom donating sperm/egg from signing of informed consent through 180 days after thelast dose of study treatment.

6. Able to provide tumor tissue sample (archival or newly obtained core orexcisional biopsy) at biomarker-screening (for NSCLC in both Part 1 and 2) orscreening (for non-NSCLC in Part 1) visit of a tumor lesion not previouslyirradiated for CDH6 testing.

Exclusion Criteria:

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

2. Any other malignancy within 2 years prior to the first dose of the studytreatment except for localized cancers that are considered to have been curedand in the opinion of the Investigator present a low risk for recurrence.

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

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

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

6. Uncontrollable pleural effusion, pericardial effusion, or ascites requiringdrainage or medical intervention within 4 weeks before the first dose of studytreatment.

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

8. History of non-infectious pneumonitis that has required a course of oral orintravenous steroids to assist with recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.

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

10. Major surgery within 2 weeks of receiving the first dose of study treatment.

11. Has received prior anti-cancer therapies within the following time frames priorto the first dose of study treatment; Previous cytotoxic therapy, anticancertargeted small molecules (e.g., tyrosine kinase inhibitors), hormonal agents within 2 weeks, Anti-cancer antibody or ADC within 5 half-lives or 4 weeks (whichever isshorter) prior to the first dose of study treatment, Chinese medicines/herbalpreparations with anticancer indication taken within 2 weeks and/or Radiationtherapy <4 weeks.

12. Use of any live vaccine therapy within 4 weeks prior to the first dose of studytreatment.

13. Administration of below medications≤14 days prior to the first dose of SIM0505;Strong and moderate CYP3A4 inhibitors and Drugs with known risk of Torsades dePointes (TdP).

14. Known human immunodeficiency virus (HIV) infection or known acquiredimmunodeficiency syndrome (AIDS).

15. Active hepatitis B or hepatitis C infection 18. Participants with clinicallysignificant cardiovascular diseases. 19. History of allogeneic organ transplantationor graft-versus-host disease. 20. Known hypersensitivity to study drug or any of theexcipients. 21. Participant is pregnant or breastfeeding. 22. Other conditions thatresearchers consider inappropriate for inclusion.