A Safety Study of PF-08046044/SGN-35C in Adults With Advanced Cancers

Inclusion Criteria:

• Tumor type

• For dose escalation and back fill and dose optimization (Parts A and B):

• Participants with a histologically confirmed lymphoid neoplasm who in thejudgement of the investigator have no appropriate standard therapy available atthe time of enrollment and are a candidate for PF-08046044/SGN- 35C treatment.Eligible subtypes and treatment status are as follows:

• Participants with relapsed/refractory (R/R) cHL: should have received atleast 3 prior systemic therapies including autologous stem cell transplant [ASCT] (ASCT and the associated high-dose chemotherapy prior to ASCT areconsidered to be 1 prior line, along with post-transplant consolidation ifprogression has not occurred between transplant and start ofconsolidation) or an anti-PD-1 agent (or refused/were ineligible); or 2prior systemic therapies if, according to the investigator, no otherappropriate standard treatment is available.

• Participants with R/R PTCL (excluding systematic anaplastic large celllymphoma [sALCL]): should have received at least 2 prior systemictherapies, or 1 prior systemic therapy if, according to the investigator,no other appropriate standard treatment is available.

• Participants with R/R sALCL: should have received at least 2 priorsystemic therapies, including 1 brentuximab vedotin-containing regimen, or 1 prior line of systemic therapy including brentuximab vedotin,cyclophosphamide, doxorubicin, and prednisone.

• Participants with R/R DLBCL: should have received at least 2 priorsystemic therapies, including ASCT and chimeric antigen receptor (CAR)T-cell therapy, or were ineligible, or refused.

• Participants with PTCL and DLBCL must have a detectable cluster ofdifferentiation 30 (CD30) expression level (≥1%) in tumor tissue from the mostrecent biopsy obtained at or after relapse by local testing.

• For dose expansion (Part C):

• Participants are eligible irrespective of CD30 expression on tumor tissue;however, participants must provide tumor tissue for evaluation of CD30expression from the most recent biopsy obtained at or after relapse.

• Participants with cHL, PTCL, sALCL, and DLBCL: Eligible subtypes are the sameas defined in Parts A and B

• If activated, the biology cohort may enroll the populations included in PartsA, B, and C.

• Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1

• Fluorodeoxyglucose positron emission tomography (FDG-PET) avid and bidimensionalmeasurable disease as documented by radiographic technique (spiral computedtomography [CT] preferred)

Exclusion Criteria:

• Previous exposure to any antibody-drug conjugates (ADCs) with camptothecin-basedpayload.

• History of another malignancy within 3 years before the first dose of study drug, orany evidence of residual disease from a previously diagnosed malignancy. Exceptionsare malignancies with a negligible risk of metastasis or death

• Active central nervous system (CNS) disease related to the underlying malignancy.Participants with a history of CNS disease related to the underlying malignancy areallowed if prior CNS disease has been treated and the participant is clinicallystable (defined as not currently receiving steroid treatment for symptoms related tocerebral/meningeal disease and with no ongoing related AE).

• Received previous ASCT infusion <12 weeks prior to the first dose of SGN-35C.

• Previous allogeneic stem cell transplant (SCT) if they meet any of the followingcriteria:

• <100 days from allogeneic SCT. Participants ≥100 days from allogeneic SCT whoare stable without immunosuppressive therapy for at least 12 weeks arepermitted.

• Active acute or chronic graft-versus-host disease (GVHD) or receivingimmunosuppressive therapy as treatment for or prophylaxis against GVHD.

• History of clinically significant GI bleeding, intestinal obstruction, or GIperforation within 6 months of initiation of trial treatment.