• Signed the informed consent voluntarily and agreed to follow the program requirements

• Either sex

• Age: ≥18 years

• Has a life expectancy of ≥3 months

• Has histologically documented, incurable, locally advanced or metastatic epithelial origin malignant cancer, priority to include the following tumor types: NSCLC, HER2 - breast cancer, esophageal cancer, SCLC, NPC, and HNSCC.

• Has documented locally advanced or metastatic HER2 negative (by immunohistochemistry \[IHC\], score of 0 or 1) Hormone Receptor (HR) positive (HER2-, HR+) OR HER2 negative (IHC score of 0 to 2) HR negative breast cancer (HER2-, HR-) as per ASCO CAP criteria (ASCO CAP 2023; Wolff et al. 2023), not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease, must have received 1 prior line of chemotherapy for advanced disease and, when applicable and if approved in that region, a PD-1/PD-L1 inhibitor, either given concurrently or sequentially. When appropriate, must have progression on at least 1 prior line of hormonal therapy with or without a targeted therapy (such as CDK4/6, mTOR, or PI3-K inhibitors) administered for treatment of metastatic disease.

• In Dose Escalation and Dose finding portions of the study, for triple-negative breast cancer (TNBC, HER2-/HR-) participants must have received PARP inhibitors if a BRCA mutation is present and sacituzumab govitecan as second line treatment. Participants who are HER2 low must have received trastuzumab deruxtecan.

• Agree to provide archived tumor samples (tissue block or slides) from primary or metastatic sites within 2 years. In the event that no archival tissue is available a fresh tissue biopsy is highly encouraged but not mandatory.

• Has at least one measurable lesion based on RECIST V1.1 (with the exception of Prostate adenocarcinoma cohort, where subjects with bone metastasis are allowed)

• Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1

• Toxicity of previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0 (except for asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, elevated serum or plasma amylase/lipase, and elevated blood glucose; except for toxicity that the investigator determined to have no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, hypothyroidism stabilized by hormone replacement therapy, etc.)

⁃ Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%

⁃ Has adequate organ function before registration, defined as: a) Marrow Function: Absolute neutrophil count (ANC) ≥1.2×109 /L, Platelet count ≥100×109 /L, Hemoglobin (Hb) ≥90 g/L b) Hepatic function: Total bilirubin（TBIL≤1.5 ULN, AST and ALT without liver metastasis ≤2.5 ULN, AST and ALT with liver metastasis ≤5.0 ULN c) Renal function: Creatinine clearance ≥50 mL/min (According to the Cockcroft and Gault equation)

⁃ Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN

⁃ Urinary protein ≤2+ or ≤1000mg/24 hours

⁃ Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for 7 months for females and 4 months for males after the last dose of study treatment. An additional contraceptive method, such as a barrier method like a condom is required.

⁃ Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female subjects are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes. In addition, females \<55 years old must have a serum follicle stimulating hormone (fsh) level \> 40 mIU/mL to confirm menopause.

⁃ For subjects with NSCLC (EGFR mutation):

⁃ a) Evidence of documented EGFR TKI-sensitizing deletion mutation in EGFR Exon 19 (ex19del) or leucin-arginine substitution point mutation in EGFR Exon 21 (ex21L858R), the serine-isoleucine mutation in EGFR Exon 20 (ex20S768I), the leucine-glutamine substitution mutation in Exon 21 (ex21L861Q), or the glycine substitution (with alanine, cysteine, or serine) mutation in Exon 18 (ex18G719X) at or after the time of disease diagnosis and prior to initiation of treatment.

⁃ For Triple-Negative Breast Cancer (TNBC, HER2-/HR-):

⁃ a) Histologically or cytologically confirmed and documented locally advanced, recurrent inoperable or metastatic TNBC

⁃ For Esophageal adenocarcinoma

⁃ a) Has locally advanced or metastatic adenocarcinoma cell carcinoma of the esophagus or esophagogastric junction cancers, not amenable to curative surgery or radiation with documentation of radiological disease progression after one line of fluoropyrimidine and/or platinum-based chemotherapy treatment regimen for locally advanced or metastatic disease.

⁃ NOTE: Prior therapies such as trastuzumab, zolbetuximab, or IOs are allowed in the study.

⁃ For Prostate adenocarcinoma

⁃ a) Subject has metastatic castration-resistant prostate cancer (mCRPC) after progression on/after an androgen receptor pathway inhibitors (ARPI) treatment, such as abiraterone, enzalutamide, apalutamide and darolutamide.

⁃ Note: No prior chemotherapy including docetaxel is allowed Prior treatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) is allowed. Enrollment will be capped for lutetium Lu 177 vipivotide tetraxetan-naive participants at approximately 20 or participants with prior lutetium Lu 177 vipivotide tetraxetan treatment at approximately 20.

⁃ For NSCLC (EGFR wild type) with squamous histology

∙ Has documented locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease with predominantly squamous cell histology

‣ Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1).

‣ Progressed or intolerant to one line of platinum-based chemotherapy with α-PD-1/L1 monoclonal antibody given either concurrently or sequentially.

⁃ For NSCLC (EGFR wild type) with adenocarcinoma histology

∙ Has documented locally advanced or metastatic NSCLC, not amenable to curative surgery or radiation with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease with predominantly adenocarcinoma histology

‣ Must have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Must have no known genomic alterations in ROS proto-oncogene 1 (ROS1).

⁃ Progressed or intolerant to one line of platinum-based chemotherapy with α-PD-1/L1 monoclonal antibody given either concurrently or sequentially.

⁃ Ovarian adenocarcinoma

⁃ a) Has histologic documentation of epithelial ovarian, primary peritoneal, or fallopian tube cancer that has progressed or relapsed on or after a previous platinum-containing chemotherapy with or without a PARP inhibitor.

⁃ Note: participants with platinum-sensitive or platinum resistant recurrent ovarian cancer (PSR) are eligible. However, enrollment will be capped for platinum-sensitive or platinum resistant participants at approximately 20 each.

⁃ Prior bevacizumab treatment is allowed.

⁃ Endometrial carcinoma

⁃ a) Has relapsed, advanced and/or metastatic endometrial carcinoma, who have progressed on or after prior platinum-based chemotherapy with or without immuno-oncology (IO) treatment

⁃ For Cervical carcinoma Has relapsed, advanced and/or metastatic cervical carcinoma, who have progressed on or after prior platinum-based chemotherapy with or without immuno-oncology (IO) treatment