A Phase 1-2 Dose-escalation and Expansion Study of ST101 in Patients With Advanced Unresectable and Metastatic Solid Tumors

⁃ Able and willing to sign informed consent form (ICF) and comply with the protocol and the restrictions and assessments therein.

• Male or female ≥18 years of age.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• Must have a locally advanced or metastatic inoperable tumor as follows:

∙ For the dose escalation/regimen exploration phase: melanoma, carcinoma, or sarcoma

‣ For the expansion phase: HR positive LA/MBC, melanoma, GBM, CRPC

• Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be biopsied based on the investigator's assessment) prior to the start of study treatment, and to repeat biopsy once during study treatment. Tissue obtained for the biopsy must not be previously irradiated (unless progressing following irradiation), but a new or progressing lesion in the radiation field is acceptable. Archived biopsies are acceptable for GBM patients.

• In the investigator's opinion, the patient may not derive clinical benefit from, or is ineligible for, a particular form of standard therapy on medical grounds, or the patient failed or did not tolerate one or more of other anti-cancer therapies:

⁃ a. For the dose escalation/regimen exploration phase up to 3 previous lines of systemic anticancer therapies are allowed. Since this is a FIH study, it's important that patients are not refractory to therapeutic intervention due to multiple lines of prior therapies.

⁃ a. For the expansion phase: i. HRpos LA/MBC must have progressed after prior 1-2 hormone-based therapies. Previous treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, mammalian target of rapamycin (mTOR) inhibitor or chemotherapy is allowed as monotherapy or in combination ii. Melanoma that has progressed after or on treatment with a CPI and have received 1-2 prior lines of therapy for their advanced/metastatic disease. Patients that have BRAF mutated disease should also have received one line of appropriate targeted therapy iii. Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen (surgery, radiotherapy, and temozolomide therapy). Patients that undergo tumor treating fields as an adjuvant to first line therapy are allowed.

⁃ iv. CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide or that are intolerant to these treatments.

• Evaluable disease per RECIST 1.1, modified RANO or PCWG3 with at least one target lesion

• Disease that progressed on, or is non-responsive to, the previous line of therapy per RECIST 1.1, modified RANO or PCWG3.

• If not menopausal or surgically sterile, willing to practice at least one of the following highly effective methods of birth control for at least a (partner's) menstrual cycle before and for four months after ST101 administration: (1) total abstinence from sexual intercourse with a member of the opposite sex; (2) sexual intercourse with vasectomized male/sterilized female partner; (3) combined (estrogen and progestogen containing) or progestogen-only hormonal contraception associated with inhibition of ovulation (oral, parenteral, transvaginal or transdermal) for at least 3 consecutive months prior to investigational product administration; (4) other acceptable forms of birth control (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicide or cream); (5) use of an intrauterine contraceptive device.

⁃ All previous anti-cancer therapy-related adverse events should have resolved to grade 1 or baseline value with the exception of alopecia. Levothyroxine is allowed for patients that previously received a CPI and experienced thyroid dysfunction.