A Study of DB-1310 in Advanced/Metastatic Solid Tumors

Exclusion Criteria

• •1. Prior treatment with HER3 targeted therapy.
• •2. Prior treatment with antibody drug conjugate with topoisomerase I inhibitor (except topoisomerase I inhibitor HER2 ADC for backfilled subjects in Combo A of Phase 1 and subjects in Cohort 2e of Phase 2a, and not applicable for subjects enrolled for DLT observation in Phase 1).
• •3. Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
• •4. Has a medical history of myocardial infarction or unstable angina or cerebrovascular accident including transient ischemic attack (TIA) within 6 months before first dose. Or has uncontrolled hypertension (defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg).
• •5. Has any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiogram (ECG), e.g., complete left bundle branch block, third-degree heart block, second-degree heart block, or PR interval \> 250 milliseconds (ms).
• •6. Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) based on a 12-lead electrocardiogram (ECG) in triplicate.
• •7. Unable or unwilling to discontinue concomitant drugs that are known to prolong the QT interval.
• •For Combo B of Phase 1 and Cohort 2g, 2k of Phase 2a, patients currently receiving (or unable to stop use prior to receiving the first dose of Osimertinib) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3-week prior) (refer to Section 6.9.1) are ineligible, and all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4.
• •8. Has a history of (non-infectious) ILD/pneumonitis and/or radiation pneumonitis that required glucocorticoids, or has current ILD/pneumonitis and/or radiation pneumonitis, or where suspected ILD/pneumonitis and/or radiation pneumonitis cannot be ruled out by imaging at screening.
• •9. Have a lung-specific intercurrent clinically significant illness including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months prior to Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disorder, restrictive lung disease, significant pleural effusion etc.), and any autoimmune, connective tissue or inflammatory disorder with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis etc.), and/or prior pneumonectomy (complete).
• •10. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
• •11. Know human immunodeficiency virus (HIV) infection. Subjects should be tested for HIV prior to enrollment if required by local regulations or by the IRB/ EC.
• •12. Subjects have active viral (any etiology) hepatitis are excluded.
• •13. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by serum pregnancy tests performed within 7 days prior to Cycle 1 Day 1.
• •14. Has clinically active central nervous system (CNS) metastases, defined as untreated, or symptomatic, or requiring therapy with glucocorticoids or anticonvulsants to control associated symptoms. However, subjects with asymptomatic CNS metastases who are radiologically and neurologically stable for at least 4 weeks following CNS-directed radiotherapy or surgery, and who are on stable or decreasing doses of glucocorticoids equivalent to ≤10 mg/day prednisone are eligible for study entry.
• •15. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, grade ≤ 1 or baseline.
• •16. Has multiple primary malignancies within 5 years before enrollment, except adequately resected non-melanoma skin cancer (e.g., resected basal or squamous cell skin cancer), curatively treated in-situ disease (e.g., carcinoma in situ of the cervix or breast), other solid tumors curatively treated (e.g., \< T1 urothelial carcinoma), or contralateral breast cancer.
• •17. Has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation or evaluation of the clinical study in the opinion of the investigator.
• •18. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
• •19. Patients with other reasons that, in the opinion of the Investigator, make them unsuitable to participate in this study.
• •20. For Combo B of Phase 1 and Cohort 2g, 2k, 2m of Phase 2a, patients with refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of Osimertinib or capecitabine are ineligible.