• Identification of the maximum tolerated dose and identification of the recommended dose of XmAb2513 for evaluation in future studies. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

• Safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  
• Assessment of immunogenicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  
• Objective response rate, disease control rate, and progression free survival. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  
• Change in solCD30 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  

A Phase 1 Study of Every Other Week XmAb™2513 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma

An open-label, multi-dose, single-arm, Phase 1 dose escalation study of XmAb2513 will be conducted to define the MTD or recommended dose(s) for further study, to determine safety and tolerability, to characterize PK and immunogenicity, and to evaluate antitumor activity of XmAb2513 in patients with HL and ALCL (non-cutaneous) and who have received two or more prior therapeutic regimens. There will be no intra-patient dose escalation.

The trial target Patients who are > 18 years old with a histological diagnosis of Hodgkin Lymphoma (HL) or Anaplastic Large Cell Lymphoma (ALCL [non-cutaneous] ) and who have received two or more prior therapeutic regimens, one of which should include hematopoietic cell transplant, either autologous or allogeneic transplant.

Treatment is given every 2 weeks for 4 doses. Patients with CR/PR/SD may continue until PD or a max of 8 doses. All patients will complete 3 months of follow-up.

Administration of XmAb2513 (0.3, 1.0, 3.0, 6.0, 9.0 , 12.0 mg/kg) IV over 2 hours. Initial dosing will occur using an accelerated dose escalation design. Dose escalation will be divided into two segments: the initial accelerated escalation phase and the standard escalation phase. During the initial accelerated dose escalation phase, dose escalation may occur after treatment of one patient per cohort provided that there is no DLT and no Grade 2 or greater, treatment-related toxicity. Treatment-related is defined as probably or possibly related to study drug. The dose escalation safety assessment period will include data from the first 4 weeks of treatment (2 doses or one cycle).

At the point that a patient experiences a treatment-related DLT or treatment-related, Grade 2 or greater toxicity (based on the NCI CTCAE version 3) during the dose escalation safety assessment period, the initial accelerated escalation phase will end, the standard dose escalation phase will begin, and the cohort in which the event occurred will be expanded to a total of 3 patients (2 additional patients will be enrolled).

From this point forward the standard 3+3 dose escalation rules will apply (the standard escalation phase). If none of 3 patients have a DLT then dose escalation to the next level will occur. If 1 of the 3 patients experiences a DLT, then the cohort will be further expanded to 6 patients (3 additional patients will be enrolled). If there are no additional patients with a DLT, dose escalation to the next higher dose level will occur. During the dose escalation period, any cohort with 2 or more patients experiencing a DLT will have exceeded the MTD and there will be no further dose escalation.

Safety/tolerability will be assessed by Physical examination, clinical laboratory tests [hematology and blood chemistry, urinalysis, PT/PTT, international normalized ratio (INR)] HAHA, cytokine levels, vital signs, and toxicity assessment.

Clinical disease activity: CT of neck, chest, pelvis and abdomen will be performed at the completion of 8 weeks of therapy, CT/PET will be performed at weeks 8 and 16.

FDG PET scanning will be used to monitor anti-CD30 metabolic effects and incorporated into response criteria.

Blood samples will be analyzed for serum levels of XmAb2513 and soluble CD30. Human anti- XmAb2513 antibodies will also be monitored.

Inclusion Criteria:

• Diagnosed with HL or ALCL.
• Patients must provide tumor tissue for confirmation of histologic diagnosis and presence of CD30 in the tumor tissue. Archived paraffin embedded samples are acceptable for patients who have no prior exposure to another anti-CD30 therapy and samples should be provided from the most recent biopsy and if possible from the original biopsy as well. Patients who have previously received anti-CD30 regimens must also have a biopsy performed and assessed for CD30 expression prior to study enrollment to confirm the presence of CD30 in the tumor tissue. The biopsy may be performed during the screening period or may have been performed after progression from the last anti-tumor therapy was completed.
• Patients who have previously received any targeted anti-CD30 therapies are eligible provided that the therapy was completed at least 6 months prior to enrollment, there is no residual toxicity, and there is evidence of CD30 positivity on recent or new biopsy. Additionally, these patients must be negative for anti-XmAb2513 antibodies.
• Patients should have at least one radiographically measurable site of disease of 1.5 cm in the largest dimension.
• Patients must have completed all anti-cancer treatment > 4 weeks prior to enrollment. Patients who have received a hematopoietic cell transplant must have completed immunosuppressive treatment, including systemic corticosteroids for > 3 months prior to enrollment.
• Patients must have received two or more prior therapeutic regimens, one of which should include hematopoietic cell transplant, either autologous or allogeneic transplant.
• Patients must be 18 years of age.

• Required baseline laboratory data:

  • Platelet count 80,000/mm3 (patients must not be platelet transfusion-dependent as evidenced by maintenance of platelet count above 50,000/mm3 in the 28 days prior to enrollment without transfusion)
  • Absolute neutrophil count > 1,500/mm3
  • Creatinine ≤ 1.5 times ULN
  • ALT (SGPT) /AST (SGOT) ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times ULN
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

Exclusion Criteria:

• Patients receiving treatment with an investigational agent, concurrently or within 28 days prior to dosing in this study.
• Patients with known HL or ALCL involvement of either the leptomeningeal or central nervous system.
• Patients who received prior anti-CD30 therapy AND with anti-XmAb2513 antibodies in serum detected by the Xencor screening assay.
• Patients requiring treatment with oral or intravenous corticosteroids or other oral or intravenous immunosuppressive agents.
• Patients that have been designated Class III or IV by the New York Heart Association criteria.
• Patients with a history of myocardial infarction or stroke within the last 6 months.
• Patients with known hypersensitivity to any excipient contained in the drug formulation.
• Patients with active infection are not eligible. This includes patients requiring anti-infective treatment during the 4 week period prior to enrollment. Patients on prophylactic anti-infective agents will be eligible provided they have no signs of active infection.
• Patients who are known to be HIV, Hepatitis B, or Hepatitis C positive.
• Patients with a history of prior malignancy other than HL or ALCL that have not been in remission for greater than 5 years, with the exception of basal or squamous skin carcinoma, cervical carcinoma in situ on biopsy, or localized prostate cancer (Gleason score < 5).
• Patients who are pregnant or breastfeeding.
• Patients with major surgery or radiation therapy within four weeks prior to enrollment.