Study of Brentuximab Vedotin (SGN-35) in Pediatric Participants With Relapsed or Refractory (r/r) Systemic Anaplastic Large-Cell Lymphoma or Hodgkin Lymphoma

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is
being tested to treat children who have relapsed or refractory (r/r) anaplastic large-cell
lymphoma (sALCL) or Hodgkin lymphoma (HL). This study will look at the maximum tolerated dose
and/or recommended phase 2 dose, safety and pharmacokinetics of brentuximab vedotin along
with overall response of people who took brentuximab vedotin.

The study enrolled 36 patients. In the phase 1 portion of the study, 12 participants were
enrolled to receive brentuximab vedotin 1.4-1.8 mg/kg, 30-minute IV infusion, Day 1 of every
21-day cycle, until there was evidence of disease progression or unacceptable toxicity.

Once the maximum tolerated dose and/or recommended phase 2 dose and pharmacokinetics of
brentuximab vedotin was reached, participants were enrolled by diagnosis into two phase 2
study arms: relapsed or refractory sALCL or relapsed or refractory HL and received
brentuximab vedotin 1.8 mg/kg as 30-minute IV on Day 1 of every 21-day cycle for up to 16
cycles. One participant received a maximum of 20 cycles at the joint discretion of the
sponsor and the investigator for continued clinical benefit.

This multicenter trial is being conducted worldwide. The overall time to participate in this
study is approximately 5 years. Participants made multiple visits to the clinic, and were
contacted by telephone every 12 weeks for 12 months after the end of treatment (EOT) for
progression free survival and then every 6 months until death, study closure, or 2 years
after enrollment of the last participant for overall survival.

Inclusion Criteria:

- Male or female participants aged 2 to <18 years (5 to <18 years for Hodgkin lymphoma
[HL])

- Diagnosis of systemic anaplastic large-cell lymphoma (sALCL), or HL for which
standard, curative, life-prolonging, or palliative treatment does not exist or is no
longer effective

- Participants with sALCL must have documented anaplastic lymphoma kinase (ALK) status
and must be beyond first remission or refractory to front-line chemotherapy

- Participants diagnosed with any relapsed or refractory CD30+ hematologic malignancy
(e.g., primary mediastinal B-cell lymphoma) may be included in phase 1 of the study

- Participants with HL must be in their second of later relapse, have failed systemic
chemotherapy either as induction therapy for advanced stage disease or salvage
therapy, and were ineligible for, refused, or previously received a stem cell
transplant

- Performance score ≥ 60 from Lansky Play Performance Scale if ≤16 years

- Negative pregnancy test

- Fertile Participants must use 2 effective methods of contraception prior to and
through 6 months after the last dose of the study drug

Exclusion Criteria:

- Current diagnosis of primary cutaneous ALCL (those with systemic ALCL are eligible)

- Received an allogeneic stem cell transplant <3 months prior to the first dose of study
medication, or presence of polymerase chain reaction (PCR)-detectable cytomegalovirus
(CMV) in any post-allogeneic transplant participant

- Receiving immunosuppressive therapy

- Receiving systemic therapy for chronic graft-versus-host disease (topical therapy is
allowed)

- Previous treatment with any anti-CD30 antibody

- Therapeutic monoclonal antibody use within the longer of 6 weeks or 5 plasma
half-lives

- Systemic cardiac disease that would, in the opinion of the investigator or medical
monitor, interfere with assessment of efficacy or safety of the drug

- History of another primary malignancy not in remission for at least 3 years (the
following are exempt from the 3-year limit: nonmelanoma skin cancer and cervical
carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)

- Known active cerebral/meningeal disease, including signs or symptoms of progressive
multifocal leukoencephalopathy (PML) or any history of PML

- History of cirrhosis

- Active systemic viral, bacterial, or fungal infection requiring antimicrobial,
antiviral therapy or antifungal therapy within 2 weeks prior to the first dose of
study drug (routine antimicrobial prophylaxis is acceptable)

- Concurrent therapy with other anti-neoplastic or experimental agents

- Systemic corticosteroid therapy <7 days prior to first dose of the study medication

- Any serious underlying medical condition that, in the opinion of the investigator or
medical monitor, would impair their ability to receive or tolerate the planned
treatment

- Known hypersensitivity to recombinant proteins, murine proteins, or any excipient
contained in the drug formulation

- Received nitrogen mustard agents, melphalan, or BCNU therapy within 6 weeks prior to
the first study dose

- Prior autologous hematopoietic stem cell infusion <4 weeks prior to first study dose

- Grade 2 or greater unresolved toxicity from prior antineoplastic therapy

- Grade 2 or greater peripheral neuropathy

- Female participants who are both lactating and breastfeeding, or have a positive serum
pregnancy test during the screening period or a positive urine pregnancy test on Day 1
before the first dose of study drug

- Received local palliative radiation therapy <14 days prior to the first dose of study
medication

- Received radiation therapy to more than 25% of the bone marrow-containing spaces < 84
days prior to first dose of study medication

- Received a strong or listed moderate inhibitor of CYP3A4 <2 weeks prior to first study
dose

- Participants must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study