DB-1311 in Combination with BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors

Prior treatment

• Prior treatment with B7H3 targeted therapy.
• Prior treatment with antibody-drug conjugate with topoisomerase inhibitor (e.g., trastuzumab deruxtecan).
• Is a candidate to locoregional treatment (including surgical resection, stereotactic radiation therapy or tumor ablation) with potential to induce complete or near complete response and prolonged tumor control (sometimes described as “radical” intent), per investigator’s assessment.
• Has an uncontrolled concomitant or intercurrent illness, that in the opinion of the investigator, contra-indicates trial participation, limits compliance with trial procedures or substantially increases the risk of incurring AEs, including conditions specified in Section 5.4 of the protocol.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline. Toxicities that have resolved with sequelae (e.g., tracheostomy, chronic use of feeding tube, replacement hormones) are allowed, if not associated with increased risk of complications per investigator’s assessment.
• Use of any IMP within 28 days or five half-lives if known (whichever is longer) before administration of first dose of trial treatment or ongoing participation in the active treatment phase of another interventional clinical trial or prior randomization or treatment in a previous trial with the same IMPs as the current trial, regardless of treatment assignment.

Other illness

• Has a medical, psychological, or social condition or substance abuse which, in the opinion of the investigator, could compromise their wellbeing if they participate in the trial, or that could prevent, limit, or confound the protocol-specified assessments or procedures, or that could impact adherence to protocol-described requirements.
• Has uncontrolled or significant disease or disorder, or history of specific diseases and disorders, as detailed in Section 5.4 of the protocol.
• Has a history of allergies, hypersensitivities, or intolerance to the trial treatments including any excipients thereof.
• Has a history of another primary malignancy within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated or have a known additional malignancy that is progressing or requires treatment.

Other

• Is vulnerable individual as per ICH E6 definition, i.e., are individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. This includes all sponsor, trial site, or third party (e.g., CRO, vendor) personnel directly involved in the conduct of the trial and their family members or dependents, as well as all trial site personnel otherwise supervised by the investigator.
• Please see Section 5.4 of the protocol for additional Cohort/Arm-specific exclusion criteria.

• Adults aged ≥ 18 years or acceptable age according to local regulations at the time of voluntarily signing informed consent
• Are POCBP who agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the trial, starting at the time of giving informed consent and continuously until 8 months after the last dose of DB-1311 or DB-1305, or until 6 months after the last dose of BNT327, whichever occurs last.
• Are males who are fertile or if they are potentially fertile (i.e., are not surgically [e.g., have had a vasectomy] or congenitally sterile) and sexually active with a partner of childbearing potential, who agree to use condoms and to ask their female sexual partners to practice a highly effective form of contraception during the trial, starting at the time of giving informed consent and continuously until 5 months after the last dose of DB-1311 or DB-1305, or until 6 months after the last dose of BNT327, whichever occurs last.
• Are potentially fertile males who are willing to refrain from sperm donation, starting at the time of giving informed consent and continuously until 5 months after the last dose of DB-1311 or DB-1305, or until 6 months after the last dose of BNT327, whichever occurs last.
• Please see Section 5.3 of the protocol for additional Cohort/Arm-specific inclusion criteria.
• At least one measurable lesion as assessed by the Investigator according to RECIST v1.1 criteria.
• Has a life expectancy of ≥ 3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 (see Section 8.4.3 of the protocol for details).
• Has adequate organ function within 7 days prior to enrollment/randomization, as defined in Section 5.3 of the protocol.
• Has adequate treatment washout period prior to the first dose of trial treatment, as defined in Section 5.3 of the protocol. Previous effective treatment will not be discontinued due to study participation.
• Is capable of comprehending trial procedures and risks outlined in the informed consent and able to provide written consent and agree to comply with the requirements of the trial and the schedule of assessments.
• Are POCBP (participant of childbearing potential) who have a negative serum beta-hCG pregnancy test.
• Are POCBP who agree to practice a highly effective form of contraception and to require their male partners to use condoms starting at the time of giving informed consent and continuously until 8 months after the last dose of DB-1311 or DB-1305, or until 6 months after the last dose of BNT327, whichever occurs last.