DS1025a: first-in-human test in advanced solid tumors

To be eligible to participate in this trial, an individual must meet all the following criteria:

1. Sign and date the main ICF, prior to the start of any trial-specific procedures.
2. Adults ≥18 years of age at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is \>18 years old).
3. Histologically documented, advanced, metastatic, or unresectable solid tumors.
4. Relapsed from, refractory to, or intolerant to appropriate therapies to provide clinical benefit for their condition as assessed by their physician and/or investigator.
5. Is willing to provide an adequate tumor tissue sample for biomarker analyses, as follows:

   1. An adequate archival tumor tissue sample obtained within 24 months prior to informed consent is available; or
   2. If adequate archival tumor tissue is not available, the participant is willing and able to undergo a fresh pretreatment tumor biopsy. The fresh biopsy will be performed only after the Investigator has confirmed that all other eligibility criteria are met and before the first administration of trial intervention on C1D1, provided that the procedure is considered clinically appropriate and at an acceptable risk by the Investigator.
6. Has measurable disease based on local CT/MRI imaging as assessment by the Investigator using RECIST v1.1; radiographic tumor assessment must be performed within 28 days prior to initiation of trial intervention.
7. ECOG PS of 0 or 1 assessed no more than 28 days prior to initiation of trial intervention.
8. Has adequate organ and bone marrow function as assessed by local laboratory within 28 days prior to initiation of trial intervention as defined in the protocol.
9. A WOCBP is eligible to participate if the following conditions are met:

   * Participant is not pregnant as confirmed by highly sensitive pregnancy test
   * Participant does not plan to breastfeed during the Trial Intervention Period and for at least 8 months after last dose of trial intervention.
   * Participant agrees to adhere to a contraceptive method that is highly effective with low user dependency only and agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during the Treatment Period and for at least the time needed to eliminate the trial intervention after the last dose.
10. A male participant capable of producing sperm is eligible to participate if he agrees to the following during the intervention period and for at least the time needed to eliminate the trial intervention:

    * Agree not to donate sperm.
    * Adhere to approved contraception method as specified in the protocol.

An individual who meets any of the following criteria will be excluded from participation in this trial:

1. Prior treatment with an anti-CD25 therapy.
2. Treatment discontinuation history due to toxicity to a DXd-ADC agent and considered not able to tolerate DS1025a based on the discussion between the investigator and the Sponsor (for participants who have DXd-ADC treatment history).
3. Inadequate washout period before initiation of trial intervention as specified in the protocol.
4. Has spinal cord compression or clinically active central nervous system tumors, including metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
5. Uncontrolled or significant cardiovascular disease as specified in the protocol.
6. Any of the following within the past 6 months prior to initiation of trial intervention: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
7. Participants with any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, or current ILD, or suspected ILD, or ILD that cannot be ruled out by imaging at screening.
8. Lung-specific intercurrent clinically significant illnesses as specified in the protocol.
9. Has clinically significant pulmonary compromise or requirement for supplemental oxygen.
10. History of other active malignancy within 3 years prior to initiation of trial intervention, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate \>90%) and treated with expected curative outcome
11. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 6.0, Grade ≤1 or baseline.
12. History of hypersensitivity to any excipients in DS1025a or any known contraindication to treatment with, including hypersensitivity to, the trial intervention.
13. Has a known history of HLH.
14. Has a known active infection, or reactivation of latent following infections as specified in the protocol among participants who received treatment such as antivirals, antifungals, or IV antibiotics within 14 days prior to first dose of trial intervention.
15. Has active or uncontrolled HBV infection.
16. Has active or uncontrolled HCV infection.
17. Has active or uncontrolled HIV infection.
18. Has an active, known, or suspected autoimmune disease.
19. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10 mg daily prednisone equivalents) or any other form of immunosuppressive therapy within 14 days prior to the trial intervention.