A Safety Study of SGN-2FF for Patients With Advanced Solid Tumors

This is a phase 1, open-label, multicenter, dose escalation study that will examine the
safety profile of SGN-2FF given orally to patients with advanced solid tumors. The primary
goal of the study is to identify the maximum tolerated dose (MTD), or optimal biological dose
(OBD) that does not exceed the MTD. The pharmacokinetics (PK) and antitumor activity of
SGN-2FF will also be evaluated. In this study, SGN-2FF will be evaluated as monotherapy and
as combination therapy with the standard approved dose of pembrolizumab.

The monotherapy portion of the study will be conducted in 2 sequential parts (Part A and Part
B). Part A will enroll patients for dose escalation to estimate the MTD /OBD and help
determine the dosing regimen that will be tested in Part B. The OBD will be evaluated by
assessing the activity of SGN-2FF, including pharmacodynamics, PK, and other observations in
dose escalation. Part B will explore the recommended dose/regimen in up to 3 focused
expansion cohorts.

The combination therapy portion of the study will be conducted in 2 sequential parts (Part C
and Part D). SGN-2FF will be administered orally according to the dose and schedule assigned,
with a lead-in period of 2 weeks prior to pembrolizumab administration. The lead-in period
may be discontinued based on emerging nonclinical and/or clinical data. Part C will enroll
patients for dose escalation to estimate the MTD /OBD and the dosing regimen that will be
tested in Part D. Part D will explore the recommended dose/regimen in up to 3 focused
expansion cohorts.

Safety will be monitored throughout the trial by the safety monitoring committee which will
meet frequently to review the emerging safety data and make dose-escalation and
dosing-interval recommendations. Antitumor activity will be assessed by radiographic imaging.
Patients may continue treatment until progression of their disease or intolerable side
effects.

Retreatment with SGN-2FF monotherapy or with SGN-2FF and pembrolizumab combination therapy is
permitted with medical monitor approval for patients who achieve stable disease, a complete
response, or partial response on study and then experience disease progression after
discontinuing prior treatment with SGN 2FF.

Inclusion Criteria:

- Patients with histologically or cytologically-confirmed, locally advanced, or
metastatic solid malignancy that is relapsed, refractory, or progressing following at
least 1 prior systemic therapy (Part A)

- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as
defined by RECIST 1.1

- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
1

- Patients in Part B must have histologically or cytologically-confirmed,
locally-advanced, or metastatic solid malignancy within the disease indications of
Part A

- Adequate baseline hematologic, renal, and hepatic function

- Patients for whom there is no further standard therapy available at the time of
enrollment (Part A)

- Patients with a histologically-confirmed, advanced solid malignancy meeting one of the
following criteria: (1) indication for which pembrolizumab is approved or (2)
relapsed, refractory, or progressive disease following at least 1 prior therapy and
for which no further standard therapy is a available (Parts C and D)

Exclusion Criteria:

- Patients with carcinomatous meningitis or active central nervous system (CNS)
metastases

- Patients with recent (within 14 days) or serious ongoing infection

- Patients requiring systemic treatment with corticosteroids (greater than 10 mg
prednisone equivalents) or immunosuppressive medications within 14 days of enrollment

- Patients with active known or suspected autoimmune disease or significant
autoimmune-related toxicity from prior immuno-oncology therapy

- Known active or latent tuberculosis

- Uncontrolled diabetes mellitus

- History of interstitial lung disease

- Gastrointestinal abnormality that would affect absorption of SGN-2FF

- Patients tested positive for hepatitis B or with a known, active hepatitis C infection

- Women who are pregnant or breastfeeding

- Patients with deep vein thrombosis (DVT)

- Contraindication to prophylactic anticoagulation