Medical Access Program for DS-9606a (DS-9606) in Patients With Advanced Testicular Germ Cell Tumors

Patients are only eligible after signing the informed consent form (ICF) (see also signature by an impartial witness) and must meet all of the following criteria to be eligible for the MAP:

1. Sign and date the ICF prior to the start of any trial- specific qualification procedures.

2. All patient must be Male adults ≥18 years or the minimum legal adult age (whichever is greater) at the time the ICF is signed.

   The patient with histologically or cytologically documented advanced/metastatic testicular GCT, including seminoma, non-seminoma, and mixed histology type, defined as patients who have progressed after at least 2 prior lines of platinum-based chemotherapy. Progression may be assessed based on radiographical progression and/or elevation of tumor markers (AFP and/or HCG). Prior HDCT with SCT is allowed but not required for program entry. Retroperitoneal GCT that are considered to be from testicular origin are eligible.

3. The patient has an ECOG PS of 0 or 1.

4. The patient meets required BL local laboratory data (within 14 days prior to C1D1) as specified in the protocol. Growth factors/transfusions are not allowed 2 weeks before SCR laboratory assessments.

5. The patient, if 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 program intervention. The length of time required to continue contraception after last dose for the trial intervention is 195 days (approx. 6.5 months).

   • Avoid donating sperm.

   • Adhere to either of the following contraception methods:

     • True abstinence from penile-vaginal intercourse, when this is in line with the preferred and usual lifestyle of the patient, OR
     • Uses a penile/external condom when having penile-vaginal intercourse with a NPOCBP PLUS partner use of an additional contraceptive method, as a condom may break or leak.

   Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the program interventions are more stringent than the requirements above, the local label requirements are to be followed.

6. The patient is willing and able to comply with scheduled visits, program intervention administration plan, laboratory tests, other program procedures, and program restrictions.

Patients who meet any of the following criteria will not be eligible for the MAP.

1. The patient has a known secondary malignancy arising from teratoma (e.g, Teratoma with malignant transformation) actively part of the current GCT disease.
2. The patient has received prior therapy with other CLDN6-targeted agents or ADC that delivers PBD payload.
3. The patient has an inadequate washout period before C1D1 as specified in the protocol.
4. The patient has clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis, defined as untreated or symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Patients with untreated stable and asymptomatic brain metastases or patients with treated brain metastases who are no longer symptomatic and who require no treatment with steroids may be included in the program if they have recovered from the acute toxic effect of radiotherapy.
5. The patient has had any of the following within the past 6 months: cerebrovascular accident, transient ischemic attack, other arterial thromboembolic event, or pulmonary embolism.
6. The patient has uncontrolled or significant cardiovascular disease as specified in the protocol.
7. The patient has a history of ILD/pneumonitis irrespective of steroid use, or current ILD, or current suspected ILD, or ILD that cannot be ruled out by imaging at screening.
8. The patient has a clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e, pulmonary emboli within 3 months of the program enrollment, severe asthma, severe COPD, restrictive lung disease, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
9. The patient uses chronic systemic corticosteroids or other immunosuppressive medications >10 mg/day of prednisone or equivalent, with exceptions as noted in protocol.
10. The patient has a history of malignancy other than disease under the program within the 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%) and have been treated with expected curative outcome (e.g., adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, ductal carcinoma in situ, or Stage I uterine cancer).
11. The patient has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute - common terminology criteria for adverse events (NCI-CTCAE) version 5.0, Grade ≤ 1 or BL.
12. The patient has a history of hypersensitivity to any excipients in DS-9606a or any known contraindication to treatment with DS-9606a, including hypersensitivity to the program intervention(s).
13. The patient has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
14. The patient has a history of capillary leak syndrome (CLS).
15. The patient has a history of clinically significant pleural or pericardial effusion, edema, or other fluid accumulation that is difficult to treat or refractory to treatment.
16. The patient has a history of nephrotic syndrome.
17. The patient has evidence of severe or uncontrolled systemic diseases (including active bleeding diatheses or active infection; psychiatric illness/social situations, substance abuse) or other factors which, in the treating physician's opinion, make it undesirable for the patient to participate in the program or which would jeopardize compliance with the protocol. SCR for chronic conditions is not required.
18. The patient has an active or uncontrolled HBV or HCV infection. Hepatitis B and C SCR testing is required.
19. The patient has an active or uncontrolled HIV infection. Patients must be tested for HIV viral load during the SCR Period if acceptable by local regulations or IRBs/IECs.
20. The patient has psychological, social, familial, or geographical factors that would prevent regular FU.
21. The patient has received live attenuated vaccines within 30 days prior to first treatment intervention.
22. The patient has had prior or ongoing clinically relevant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the treating physician's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the program intervention; or confound the assessment of program results.