HuMax-CD20 i(Ofatumumab) n Follicular Lymphoma (FL) Patients Refractory to Rituximab

Based on OR over a 6-month period from start of treatment, participants were classified as responders/non-responders as follows: participants with CR, CRu, or PR were classified as responders, whereas participants with Stable Disease (SD; achieving less than PR but not consistent with PD), Progressive Disease (PD; 50% increase from nadir in the products of the greatest perpendicular diameters of any previously identified node or appearance of any new node \>1 cm), or Not Evaluable (NE) participants were classified as non-responders.

Time frame: 6-month period from the start of treatment. There was a median time of response at Month 5.5 (participants were followed for up to 24 months).

Population: FAS

OR was assessed by an Independent endpoints Review Committee (IRC) according to the standardized response criteria for Non-Hodgkin's lymphoma. Participants with Complete Response (CR; complete disappearance of all detectable disease), Complete Response unconfirmed (CRu; any residual lymph node/nodal mass \>1.5 centimeters \[cm\] in its longest transverse diameter that regressed \>75% compared to baseline), or Partial Response (PR; \>=50% decrease in the sum of the product of diameters of indicator lesions) were defined as responders for OR.

Time frame: Start of treatment (Day 1 of Week 0) until 3 months after start of last infusion (up to Week 32)

Population: Full Analysis Set (FAS): all participants who were exposed to study drug irrespective of their compliance to the planned course of treatment

AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is AUC from the start of infusion extrapolated to infinity.

Time frame: Visit 9 (Week 7; up to 10 months after dose)

Population: FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

CL is the clearance of drug from plasma, which is defined as the volume of plasma from which drug is removed per unit time.

Time frame: Visit 9 (Week 7; up to 10 months after dose)

Population: FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

Blood samples were drawn from participants at Visits 1 and 2 for analysis of complement (CH50) levels. Analysis of CH50 was done in batches, and CH50 levels were measured two hours after the end of study medication infusion. Percent change from Screening (Visit 1, Week -2) = (value at Visit 2 minus the value at Visit 1 divided by the value at Visit 1) \* 100.

Time frame: Visits 1 (Week -2) and 2 (Week 0)

Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Cmax is defined as the maximum concentration of drug in plasma samples. Ctrough is defined as the trough plasma concentration (measured concentration at the end of a dosing interval \[taken directly before the start of the next infusion\]).

Time frame: Visit 9 (Week 7; up to 10 months after dose)

Population: FAS. Data were provided for the number of participants who had a value. Cmax was not reported for one participant due to missing data. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

The duration of response is defined as the time from the initial response (the first visit at which response was observed) to progression or death. For participants who were lost to follow-up, duration of response was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate duration of response.

Time frame: From start of treatment (Week 0) until Month 24

Population: FAS. Only those participants classified as responders were analyzed.

FcR poly. affect the affinity with which FcRs interact with immunoglobulin molecules and are prognostic factors that are indicative of altered responsiveness to treatment and/or survival. A blood sample was drawn at Visit 1 for analysis (done in batches of several samples) of FcR poly. (Fcgamma RIIIa Valine/Phenylalanine genotypes \[TT=thymidine/thymidine, TG=thymidine/guanine, GG=guanine/guanine\] and Fcgamma RIIa Arginine/Histidine genotypes \[AA=adenine/adenine, AG=adenine/guanine, GG=guanine/guanine\]). Responders must have met the criteria for CR, CRu, or PR at either Month 3 or Month 6. Fc receptor polymorphisms and C1qA-276 results are not included in this results summary.

Time frame: From first treatment (Visit 2) until Visit 12 (Month 6)

Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. A list of AEs experienced in the study at a frequency threshold of 5% can be found in the AE section.

Time frame: From first treatment (Visit 2) until Visit 18 (Month 24)

Population: FAS

B-cell lymphoma 2 (BCL2) is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. BCL2 mitochondrial ribonucleic acid (mRNA) was measured by polymerase chain reaction (PCR) from peripheral blood. Participants who had no post-screening data were categorized as Missing.

Time frame: Screening (Visit 1) until Month 24 (Visit 18)

Population: FAS. Only those participants who were BCL2 positive at Screening were analyzed.

HAHA are indicators of immunogenicity to ofatumumab. Blood samples were withdrawn from participants at Visits 1, 12, 13, and 18 for analysis of HAHA. Analysis of HAHA was done in batches.

Time frame: Visits 1 (Screening), 12 (Month 6), 13 (Month 9), and 18 (Month 24)

Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Overall survival is defined as the time from randomization until death. For participants who are lost to follow-up, overall survival will be censored at the date of the last attended visit at which the endpoint was assessed.

Time frame: First dose (Week 0) until 5 years

Population: FAS. As of the time of data cut-off, data for Overall Survival was not estimable because too few deaths have occurred at the time of study completion.

CD19 and CD20 are proteins found on the cell surface of B cells, and they can be detected in peripheral blood by flow cytometry. Flow cytometry of peripheral blood was performed for immediate analysis of cells with cluster of differentiation 19 (CD19+) and CD20+. The analysis will be done until a value is reached that is in the normal range. Percent change from Baseline (Visit 2) = (value at Visits 11 and 12 minus the value at Visit 2 divided by the value at Visit 2) \* 100.

Time frame: Visits 2 (Baseline), 11 (Month 3), and 12 (Month 6)

Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Tumor size was measured by computed tomography (CT) scan and was computed as the sum of product of diameters (SPD) for the indicator lesions. CT scans with contrast of the neck, thorax, abdomen, and pelvis were performed at Screening and during the follow-up period (Month 3, 6, 9, 12, 18, and 24). The change in tumor size from Screening (Visit 1) was presented per Radiologist 1 (R1) and Radiologist 2 (R2). Percent change from Screening (Visit 1, Week -2) = (value at Visits 11, 12, 13, 14, 16, and 18 minus the value at Visit 1 divided by the value at Visit 1) \* 100.

Time frame: Visits 1 (Week -2), 11 (Month 3), 12 (Month 6), 13 (Month 9), 14 (Month 12), 16 (Month 18), and 18 (Month 24)

Population: FAS. Data were provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Progression-free survival (PFS) is defined as the time from randomization until the first radiologically or clinically documented evidence of progression or death due to any cause, if sooner. For participants who were lost to follow-up, PFS was censored at the date of the last attended visit at which the endpoint was assessed. The Kaplan-Meier method was used to estimate PFS.

Time frame: From start of treatment (Week 0) until Month 24

Population: FAS

t1/2 is defined as terminal half-life, which is the time required for the amount of the drug in the body to decrease by half.

Time frame: Visit 9 (Week 7; up to 10 months after dose)

Population: FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data as of 28 April 2009.

Time to next FL (anti-lymphoma) therapy is defined as the time from randomization until the time of first administration of the next anti-lymphoma therapy other than ofatumumab. For participants who were lost to follow-up, the time was censored at the date of the last attended visit at which the endpoint was assessed.

Time frame: From start of treatment (Week 0) until Month 24

Population: FAS

Vss is the volume of distribution at steady state of ofatumumab.

Time frame: Visit 9 (Week 7; to up 10 months after dose)

Population: FAS. Data were provided for the number of participants for whom the parameter could be calculated. Participants withdrawn during the study were not analyzed. Interim results; data of 28 April 2009.