A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies

This is a multicenter, open-label, sequential-cohort, dose-escalation Phase 1 study of PRT543
in patients with advanced cancers who have exhausted available treatment options. Enrollment
will take place concurrently into two distinct patient groups (one for solid tumors/lymphomas
and one for hematological malignancies). The study will consist of 2 parts, a dose escalation
part, and once the recommended phase 2 dose (RP2D) has been determined, a cohort expansion
part with four separate cohorts. For patients, the study will include a screening phase, a
treatment phase, and a post treatment follow-up phase. An end-of-study visit will be
conducted within 30 days after the last dose of PRT543.

Inclusion Criteria:

- Metastatic or advanced solid tumor; or advanced diffuse large B-cell lymphoma; or
advanced mantle cell lymphoma; or relapsed myelodysplastic syndrome; or relapsed
myelofibrosis. All malignancies must be refractory to established therapies

- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

- Adequate organ function (bone marrow, hepatic, renal, cardiovascular)

- Female patients of childbearing potential must have a negative pregnancy test within 7
days of the start of treatment and must agree to use an effective method of
contraception during the trial

Exclusion Criteria:

- Primary malignancies of the Central Nervous System(CNS) or uncontrolled CNS metastases

- Requirement of pharmacologic doses of glucocorticoids

- Prior treatment with chimeric antigen receptor T cells (CAR-T cells)

- HIV positive; known active hepatitis B or C

- Known hypersensitivity to any of the components of PRT543

- Prior allogeneic bone marrow transplant; autologous hematopoietic transplantation less
than 100 days since transplantation