Safety Study of SEA-CD40 in Cancer Patients

The study will be conducted in the following parts:

Part A: Intravenous (IV) monotherapy dose-regimen finding for solid tumors --
Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to
define the IV SEA-CD40 monotherapy maximum tolerated dose (MTD) and/or the optimal biological
dose (OBD) regimens in patients with solid tumors. The ability to increase the dose intensity
(to give additional doses within a treatment cycle) may be evaluated.

Part B: IV monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor
expansion cohorts may be enrolled where patients will be treated with doses at or below the
IV SEA-CD40 monotherapy MTD and/or OBD determined in Part A.

Part C: IV monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible
dose-interval modification to lengthen the treatment cycle, to define the IV SEA-CD40
monotherapy MTD and/or the OBD regimens in patients with lymphomas. The ability to increase
the dose intensity (to give additional doses within a treatment cycle) may be evaluated.

Part D: IV monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion
cohorts may be enrolled where patients will be treated with doses at or below the IV SEA-CD40
monotherapy MTD and/or OBD determined in Part C.

Part E: Combination therapy dose-regimen finding for solid tumors -- IV SEA-CD40
dose-escalation to define the MTD and/or the OBD regimen to be administered in combination
with standard approved dose of pembrolizumab in patients with solid tumors.

Part F: Combination therapy solid tumor expansion cohorts -- Disease-specific solid tumor
expansion cohorts may be enrolled where patients will be treated with IV SEA-CD40 and
pembrolizumab combination therapy; doses of SEA-CD40 will be at or below the MTD and/or OBD
determined in Part E.

Part G: Subcutaneous (SC) injection (injected under the skin) monotherapy dose-regimen
finding for solid tumors -- Dose-escalation, and possible dose-interval modification to
lengthen the treatment cycle, to define the SC SEA-CD40 monotherapy maximum tolerated dose
(MTD) and/or the optimal biological dose (OBD) regimens in patients with solid tumors.

Part H: SC monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor
expansion cohorts may be enrolled where patients will be treated with doses at or below the
SC SEA-CD40 monotherapy MTD and/or OBD determined in Part G.

(Note: There is no Part I)

Part J: SC monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible
dose-interval modification to lengthen the treatment cycle, to define the SC SEA-CD40
monotherapy MTD and/or the OBD regimens in patients with lymphomas.

Part K: SC monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion
cohorts may be enrolled where patients will be treated with doses at or below the SC SEA-CD40
monotherapy MTD and/or OBD determined in Part J.

In Parts A, C, E, G, and J, a maximum feasible dose (MFD) will be defined if an MTD and/or
OBD cannot be identified. Parts B, D, F, H, and K will explore the recommended dosing regimen
once the MTD and/or OBD, or MFD (if the MTD and/or OBD cannot be identified) has been
determined.

Inclusion Criteria:

- (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Histologically confirmed advanced
malignancy, either: (a) Metastatic or unresectable solid malignancy; or (b) Classical
Hodgkin lymphoma (HL), or diffuse large B-cell lymphoma (DLBCL), or indolent lymphoma
(including follicular lymphoma [FL])

- (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- Relapsed, refractory, or
progressive disease, specifically: (a) Solid tumors: Following at least 1 prior
systemic therapy, and no further standard therapy is available for the patient's
advanced solid tumor at the time of enrollment; or (b) Classical HL: Following at
least 2 prior systemic therapies in patients who are not candidates for autologous
stem cell transplant (SCT), or following failure of autologous SCT; or (c) DLBCL:
Following at least 1 prior systemic therapy; patients must have also received
intensive salvage therapy unless they refused or were deemed ineligible; or (d)
Indolent lymphoma: Following at least 1 prior chemoimmunotherapy regimen that included
an anti-CD20 monoclonal antibody and for which no other more appropriate treatment
option exists

- (Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed
advanced or metastatic solid malignancy for which pembrolizumab treatment is approved.
In Part F, other advanced solid tumor indications may be eligible as identified by the
Sponsor.

- Representative baseline tumor tissue sample is available

- Measurable disease

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

- Adequate baseline hematologic, renal, and hepatic function

- Recovery to Grade 1 of any clinically significant toxicity attributed to prior
anticancer therapy prior to initiation of study drug administration

Exclusion Criteria:

- Prior chemotherapy, small molecule inhibitors, and/or other investigational anticancer
agents (excluding investigational monoclonal antibodies) within 4 weeks

- Prior radiotherapy: therapeutic radiotherapy within 4 weeks, or palliative
radiotherapy (to non-CNS disease) within 1 week

- Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology
doublet used as the prior line of therapy)

- Prior monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates within
4 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)

- Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient
experienced disease progression on the prior treatment)

- Recent or ongoing serious infections within 2 weeks

- Known positivity for hepatitis B infection

- Known active hepatitis C infection

- Active autoimmune or auto-inflammatory ocular disease within 6 months

- Known or suspected active organ-threatening autoimmune disease

- Active central nervous system tumor or metastases

- Patients with lymphomas: prior allogeneic SCT

- Patients in Part E or Part F: history of severe immune-mediated adverse reactions or
severe hypersensitivity to pembrolizumab