Trastuzumab Deruxtecan (DS-8201a) With Nivolumab in Advanced Breast and Urothelial Cancer

The purpose of this phase 1b (Phase 1/Phase 2) study is to assess the combination of a test
drug (DS-8201a) with nivolumab in participants with HER2-expressing breast and urothelial
cancer who had disease progression during or after prior therapies, did not respond to
standard therapies, or for whom no standard therapy is available.

The study will be performed in 2 parts.

- Part 1 is to test different doses of DS-8201a when given along with a fixed dose of
nivolumab, and establish the most effective and the maximum/recommended tolerated dose,
when used in combination with nivolumab

- Part 2 is to assess the efficacy and safety of this dose combination.

Inclusion Criteria:

1. Is the age of majority (adulthood) in their country

2. Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1

3. Has pathologically documented breast cancer or urothelial cancer that is unresectable
or metastatic, and refractory to or intolerant of existing therapy(ies) known to
provide clinical benefit, and as specified in each study cohort

4. Has an adequate archival tumor sample available for the central laboratory to
determine eligibility to participate

5. Has at least 1 measurable lesion per RECIST version 1.1

6. Has cardiac, bone marrow, kidney, liver, blood and clotting test results required per
protocol

7. Has had an adequate washout period before enrollment since previous surgery and other
treatment

8. If reproduction is possible, agrees to use protocol-defined methods of contraception
(or completely abstain from heterosexual intercourse) from screening to at least 5
months (females) or 7 months (males) after the last dose of study drug

9. Agrees to avoid harvesting sperm or ova for any reason from screening to at least 5
months (females) or 7 months (males) after the last dose of study drug

10. Has a life expectancy of at least 3 months

11. If eligible for Part 2, is eligible for Part 1

Exclusion Criteria:

1. Has received prior treatment with niovolumab or DS-8201a

2. Has medical history of myocardial infarction within 6 months before enrollment,
symptomatic congestive heart failure (CHF) (New York Heart Association classes II-IV),
or tropinin levels consistent with myocardial infarction 28 days before enrollment

3. Has a corrected QT interval by Fredericia (QTcF) prolongation to > 470 ms (females) or
> 450 ms (males) based on an average of the screening triplicate 12-lead
electrocardiogram

4. Has history of non-infectious interstitial lung disease (ILD)/pneumonitis (that
required steroids), has ILD/pneumonitis currently, or it cannot be ruled out by
imaging at screening

5. Has a condition (other than active autoimmune disease) that requires systemic
treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other
immunosuppressive medications within 14 days of starting study treatment

6. Is pregnant or breastfeeding, or planning to become pregnant

7. Is suspected to have certain other protocol-defined diseases based on past medical
history, physical exam, blood tests, eye test and imaging at screening period

8. Has received a live vaccine within 30 days before the first dose of study drug

9. Is related to the investigator or another employee of the sponsor or the study site

10. Is housed in an institution based on an order by the authorities or the court

11. Is pregnant, breastfeeding, or planning to become pregnant

12. Has participated in a therapeutic clinical study within 3 weeks before study drug
treatment, or is currently participating in other investigational procedures

13. Has or had any disease, psychiatric or medical condition, metastatic condition,
drug/medication use or other condition that might, per protocol or in the opinion of
the investigator, compromise:

1. safety or well-being of the participant or offspring

2. safety of study staff

3. analysis of results