A Phase 1 Multiple Ascending Dose Study of DS-3201B in Subjects with Lymphomas

DS-3201b is an experimental drug. It is not approved for regular use. It can only be used in
clinical research.

Adults with non-Hodgkin lymphoma (NHL) might be able to join this study if their disease:

- has come back after remission

- is not responding to current treatment

This study has three parts:

1. Dose Escalation is to find the safe dose of DS-3201b that adults with advanced NHL can
tolerate.

2. Dose Expansion is to:

- find out how effective DS-3201b is for rare types of NHL

- collect additional safety data

3. Drug-Drug Interaction (DDI) Cohort (US Only) is to evaluate the effect of DS-3201b on
the pharmacokinetics (PK) midazolam and digoxin when co-administered to patients with
NHL

Inclusion Criteria:

- Has hematocytological or pathological diagnosis of non- Hodgkin's lymphoma (NHL)

- Has relapsed from or is refractory to standard treatment or no standard treatment is
available

- Is the age of majority in their country (18 in the US and 20 in Japan) at the time of
informed consent

- Has Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

- Has at least one evaluable lesion site (not applicable for the DDI cohort)

- Has preserved organ function based on baseline laboratory data at screening tests

- If of reproductive potential, agrees to avoid harvesting ova or sperm, and to use a
protocol-defined form of contraception or avoid intercourse, during and upon
completion of the study, and for at least 3 months after the last dose of study drug

- Tumor biopsy collections:

1. willing to provide archived or fresh tumor tissue samples that are sufficient for
comprehensive genomic and/or proteomic analyses at baseline

2. [US only] willing to provide fresh on-treatment tumor biopsy if deemed acceptable
risk by the investigator

[Japan only] fresh on-treatment tumor biopsy should be performed if deemed
acceptable risk by the investigator

3. willing to provide optional fresh end-of-treatment biopsy

For ATL subjects:

- Has a positive test result for human T-lymphotropic virus type I antibody

- Has ATL subtype classified as acute, lymphomatous, or chronic with poor prognostic
factor

- Has diagnosis of relapse (including relapse after partial remission [PR]) or
treatment-resistant ATL at the time of informed consent after prior treatment with at
least 1 anti-cancer medication regimen

Exclusion Criteria:

- Has been diagnosed with protocol-defined cutaneous T-cell lymphoma or T-cell leukemia.
For DDI cohort, CTCL is not exclusionary.

- Has a history or presence of central nervous system (CNS) involvement

- Has a medical history, complication or other malignancy considered inappropriate for
participation in the study, or a serious physical or psychiatric disease, the risk of
which may be increased by participation in the study

- Has received drugs or other treatments not allowed by the protocol

- History of treatment with other enhancer of zeste (EZH) inhibitors

- Has had allogeneic hematopoietic stem cell transplantation (HTCP) within 90 days
before scheduled dosing on Cycle 1 Day 1

- Is pregnant or breastfeeding

- Is otherwise deemed ineligible to participate by the investigator or sub-investigator

DDI Cohort Only:

- Has received following medications within 14 days prior to study drug administration

- Any CYP3A inhibitors/inducers including weak CYP3A inhibitors/inducers, and P-gp
inhibitors, midazolam as well as digoxin