A Study of DB-1311 in Advanced/​Metastatic Solid Tumors

• Drug: DB-1311

Inclusion Criteria:

1. Male or female adults (defined as ≥ 18 years of age or acceptable age according to local regulations at the time of voluntarily signing of informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment.).
2. Histologically or cytologically confirmed unresectable advanced/metastatic solid tumor that has relapsed or progressed on or after standard systemic treatments, or is intolerable with standard treatment; or for which no standard treatment is available.
3. At least one measurable lesion as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) version 1.1 criteria. Castrate-resistant prostatea walnut-shaped gland in the male reproductive system that is responsible for producing semen - a bodily fluid that acts as a vessel for sperm transport during ejaculation cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs (CRPC) participants with bone only disease may be eligible on a case-by- case basis after discussion with the Medical Monitorto check on, keep track of.
4. Has a life expectancy of ≥ 3 months.
5. Has an Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) performance status (PS) of 0-1.
6. Has LVEF ≥ 50% by either echocardiography (ECHO) or multiple-gated acquisition (MUGA) within 28 days before enrollment.
7. Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsyremoval of a section of tissue to analyse for cancer cells for the measurement of B7-H3 level and other biomarkers if no contraindication.Note: there is no minimum B7-H3 expression level mandatory for entry into the study.
8. Is capable of comprehending study procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the study and the schedule of assessments.
9. Male and female subjects of reproductive/childbearing potential must agree to use adequate contraceptive methods (e.g., double barrier or intrauterine contraceptive) during the study and for at least 4 months and 7 months after the last dosethe amount of medication taken of study drug, respectively.
10. Male subjects must not freeze or donate sperm starting at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening and throughout the study period, and at least 4 months after the final study drug administration.
11. Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
12. SCLC participants (Phase 2a Cohort 1 ONLY):
    • Pathologically documented locally advanced, or metastatic SCLC not amenable to curative surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence or radiation.
    • Prior therapy with at least one platinum-based line as systemic therapy for extensivestage disease with at least two cycles of therapy (except in the case of early objective PD).
    • Prior treatment regimens with irinotecan, topotecan or any other TOP I inhibitor including investigational TOP I inhibitors are not allowed.
13. NSCLC participants (Phase 2a Cohort 2 ONLY):
    • Pathologically documented locally advanced, or metastatic NSCLC and is not amenable to curative surgery or radiation.
    • Has received prior treatment with platinum-based chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells regimen and/or anti-PD-1/PD-L1 antibody-based regimen in the advanced/unresectable, or metastatic setting unless unable or unwilling. Participants with NSCLC known to harbor a genomic alteration(s) other than EGFR mutation(s) (e.g., ALK rearrangement, ROS1 rearrangement, KRAS G12C mutation, BRAF V600E mutation, NTRK1/2/3 Gene fusion, MET Exon 14 skipping, RET rearrangement etc.) for which treatment is available must have also received prior treatment with at least 1 genotype-directed therapy.
14. ESCC participants (Phase 2a Cohort 3 ONLY):
    • Pathologically documented locally advanced, or metastatic ESCC and is not amenable to curative surgery or radiation.
    • Having received at least one prior therapy for unresectable disease. Patients with recurrenceto occur or happen again within 6 months of completion of neoadjuvant or adjuvant therapy will be considered as having received one prior therapy for unresectable disease.
15. CRPC participants (Phase 2a Cohort 4 ONLY):
    • Pathologically documented metastatic adenocarcinomacancer arising from mucus-producing glands in organs of the prostate cancer.
    • Progressive metastatic CRPC as defined: 1) castrate levels of serum testosterone < 50 ng/dL AND 2) progressive disease as defined by PCWG3 criteria.
    • Having received prior docetaxel (before or after an AR-targeted therapy). Docetaxel rechallenge was allowed.
    • Having received prior novel hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone.
16. Melanomaa type of cancer that develops from melanocytes, which are the cells that produce pigment generally in the skin (but can develop in other areas of the body) participants (Phase 2a Cohort 5 ONLY)• Histologically or cytologically confirmed diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of unresectable Stage III or metastatic melanoma not amenable to local therapy, must have had either:
    • Previously treated with a PD-1 or PD-L1 inhibitor.
    • If participants with BRAF gene mutant melanoma, must have had a prior treatment regimen that included vemurafenib, dabrafenib, or another BRAF gene and/or mitogen-activated protein kinase (MEK) protein inhibitor.
17. HCC participants (Phase 2a Cohort 6 ONLY)
    • Histological/cytological confirmed diagnosis of HCC or clinically confirmed diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria, and:
    • Has received 1 or 2 prior systemic therapy regimens for recurrent or metastatic disease;
    • Has experienced disease progression during or after treatment with an anti-PD-1/L1 agent administered either as monotherapy or in combination.

    Note: Subjects basically should receive prior standard therapy.

    • However, if the investigator judges the therapy is not appropriate for the subject, the prior standard therapy is not necessarily mandated for the eligibility.

18. Cervical cancer participants (Phase 2a Cohort 7 ONLY)
    • Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
    • Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either:d. paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or e. paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or f. paclitaxel + topotecan + bevacizumab + anti-PD-(L)1 agent Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the subject was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required.
    • Has received 1 or 2 prior systemic therapy regimens for recurrent or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for recurrent or metastatic cervical cancer should be counted.
19. Participants with other solid tumors (Phase 2a Cohort 8 ONLY)
    • Histologically or cytologically confirmed solid tumors.
    • Progressed or relapsed after at least one prior standard therapeutic regimen (Patients who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving DB-1311 are available prior to consenting to participate in this trial).