Trial Outcomes & Findings for A Study on Pharmacokinetics (PK), Efficacy and Safety of Subcutaneous (SC) Versus Intravenous (IV) Rituximab, in Combination With CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) in Previously Untreated Participants With CD20 Positive Diffuse Large B-Cell Lymphoma (DLBCL) (NCT NCT04660799)

Last Updated: 2023-10-12

Results Overview

For this pharmacokinetics (PK) primary outcome measure the serum rituximab Ctrough for SC and IV administrations were measured at Cycle 7, 21 days after study treatment administration for Cycle 7 (pre-dose of Cycle 8). Geometric mean ratio and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline and are reported in the statistical analysis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

50 participants

Primary outcome timeframe

At Cycle 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

Results posted on

2023-10-12

Participant Flow

This study was conducted at 9 centers in China.

Eligible participants were stratified during randomization according to International Prognostic Index (IPI) scores (IPI 0-2 = low to low-intermediate risk versus IPI 3-5 = high-intermediate to high risk). IPI risk factors include Ann Arbor Stage III or IV, age \>60 years, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance status \>/=2, extranodal involvement \>/=2.

Participant milestones

Participant milestones
Measure	Rituximab IV+CHOP Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Overall Study STARTED	24	26
Overall Study COMPLETED	17	18
Overall Study NOT COMPLETED	7	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Rituximab IV+CHOP Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Overall Study Progressive Disease	1	1
Overall Study Death	2	1
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	2	5

Baseline Characteristics

A Study on Pharmacokinetics (PK), Efficacy and Safety of Subcutaneous (SC) Versus Intravenous (IV) Rituximab, in Combination With CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) in Previously Untreated Participants With CD20 Positive Diffuse Large B-Cell Lymphoma (DLBCL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.	Total n=50 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 10.1 • n=5 Participants	55.0 years STANDARD_DEVIATION 15.5 • n=7 Participants	58.7 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Cycle 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

Population: The Per Protocol PK population included all enrolled participants who adhered to the protocol and were assigned to arms as treated. Exclusions were made for the following reasons: missing Ctrough Cycle 7 sample, Cycle 7 Ctrough sample collected with more than 3 days deviation from planned date on Day 22, given a dose that deviated from the planned dose by \>20% within 3 cycles (from Cycle 5), a Cycle 7 dose delay of more than 7 days, an assay error impacting Cycle 7 Ctrough measurement.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=19 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=24 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Subcutaneous Serum Rituximab Trough Concentration (Ctrough SC) and Intravenous Serum Rituximab Trough Concentration (Ctrough IV)	90.7 micrograms/milliliter (mcg/mL) Geometric Coefficient of Variation 21.1	137.4 micrograms/milliliter (mcg/mL) Geometric Coefficient of Variation 36.3

SECONDARY outcome

Timeframe: During Cycle 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

The area under the curve (AUC) for serum rituximab concentration versus time after dosage was measured for SC and IV administrations during Cycle 7. Geometric mean ratio and 90% confidence interval were estimated based on an ANCOVA model adjusted for tumor load at baseline and are reported in the statistical analysis.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=17 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=21 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Observed SC and IV Rituximab Area Under the Curve (AUCsc and AUCiv)	3050.7 day*mcg/mL Geometric Coefficient of Variation 17.8	3806.7 day*mcg/mL Geometric Coefficient of Variation 27.2

SECONDARY outcome

Timeframe: At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

Population: PK analyses were based on all participants with at least one PK assessment. PK analyses were analyzed as treated. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete, where the PK analysis might be influenced.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=22 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Maximum Observed Serum Concentration (Cmax) of Rituximab Cycle 2	200 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 18.3	144 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 29.6
Maximum Observed Serum Concentration (Cmax) of Rituximab Cycle 7	255 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 14.6	228 micrograms per milliliter (mcg/mL) Geometric Coefficient of Variation 28.3

SECONDARY outcome

Timeframe: At Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=22 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Time to Cmax (Tmax) of Rituximab Cycle 2	0.14 day Interval 0.09 to 0.94	5.42 day Interval 1.88 to 13.9
Time to Cmax (Tmax) of Rituximab Cycle 7	0.16 day Interval 0.1 to 1.03	1.99 day Interval 1.84 to 6.91

SECONDARY outcome

Timeframe: At Cycles 2 and 7 (one cycle=21 days), 21 days after study treatment administration, up to 21 weeks

Ctrough was measured at Cycle 2 and Cycle 7, 21 days after study treatment administration for each cycle (pre-dose of Cycle 3 and Cycle 8, respectively).

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=20 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Trough Serum Concentration (Ctrough) of Rituximab Cycle 2	43.2 mcg/mL Geometric Coefficient of Variation 26.5	63.5 mcg/mL Geometric Coefficient of Variation 36.9
Trough Serum Concentration (Ctrough) of Rituximab Cycle 7	90.7 mcg/mL Geometric Coefficient of Variation 21.1	137 mcg/mL Geometric Coefficient of Variation 36.3

SECONDARY outcome

Timeframe: During Cycles 2 and 7 (one cycle=21 days): pre-dose, within 15 minutes of end of infusion, 24 hours post-dose, Days 3, 7, 15, 21, up to 21 weeks

AUC is the area under the serum concentration curve over the dosing interval of 21 days during Cycle 2 and Cycle 7.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=20 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Area Under the Curve (AUC) of Rituximab Cycle 2	1730 day*mcg/mL Geometric Coefficient of Variation 21.5	2130 day*mcg/mL Geometric Coefficient of Variation 31.1
Area Under the Curve (AUC) of Rituximab Cycle 7	3050 day*mcg/mL Geometric Coefficient of Variation 17.8	3810 day*mcg/mL Geometric Coefficient of Variation 27.2

SECONDARY outcome

Timeframe: 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Population: The intent-to-treat (ITT) population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

Per LRC, CR based on positron emission tomography- computed tomography (PET-CT) was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, immunohistochemistry (IHC) negative.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Complete Response Rate (CRR) as Determined by the Independent Review Committee (IRC) Using Lugano Response Criteria (LRC) for Malignant Lymphoma	62.5 percentage of participants Interval 40.59 to 81.2	80.8 percentage of participants Interval 60.65 to 93.45

SECONDARY outcome

Timeframe: 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Population: The ITT population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

ORR=CR+PR. Per LRC: CR by PET-CT: complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass; no new lesions, no FDG-avid disease in bone marrow; CR by CT: complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 cm in LDi, no extralymphatic disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow; PR by PET-CT: partial MR in lymph nodes and extralymphatic sites with a score of 4 or 5 with reduced uptake compared with baseline + residual masses of any size; no new lesions, residual uptake higher than in normal bone marrow but reduced compared with baseline; PR by CT: ≥ 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 target nodes and extranodal sites; non-measured lesion absent/normal, regressed, but no increase; spleen regressed by \>50 % in length beyond normal; no new lesions.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Objective Response Rate (ORR), Complete Response (CR) or Partial Response (PR), as Determined by Investigator and IRC Using Lugano Response Criteria (LRC) for Malignant Lymphoma Investigator	70.8 percentage of participants Interval 48.91 to 87.38	88.5 percentage of participants Interval 69.85 to 97.55
Objective Response Rate (ORR), Complete Response (CR) or Partial Response (PR), as Determined by Investigator and IRC Using Lugano Response Criteria (LRC) for Malignant Lymphoma IRC	66.7 percentage of participants Interval 44.68 to 84.37	80.8 percentage of participants Interval 60.65 to 93.45

SECONDARY outcome

Timeframe: 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Population: The ITT population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

CRR was assessed according to the IWG Response Criteria for NHL 1999 guidelines and included CR and CR unconfirmed (CRu). CR was defined as complete disappearance of all clinical and radiographic evidence of disease and disease-related symptoms, regression of lymph nodes to normal size, absence of splenomegaly, and absence of bone marrow involvement. CRu was defined as disappearance of clinical and radiographic evidence of disease and absence of splenomegaly, with regression of lymph nodes by \> 75 % but still \>1.5 cm in size, and indeterminate bone marrow assessment.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
CRR, as Determined by IRC Using International Working Group (IWG) Response Criteria for Non-Hodgkin's Lymphoma (NHL) 1999 Guidelines	58.3 percentage of participants Interval 36.64 to 77.89	65.4 percentage of participants Interval 44.33 to 82.79

SECONDARY outcome

Timeframe: 6-8 weeks after the last dose of study treatment or 4-8 weeks after last dose of study treatment for early discontinuation (up to approximately 32 weeks)

Population: The ITT population consisted of all randomized participants. Participants are assigned to the treatment group to which they were randomized.

Per LRC, CR based on PET-CT was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake ≤ mediastinum; 3 = uptake \> mediastinum but ≤ liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of FDG-avid disease in bone marrow. Per LRC, CR based on CT was defined as complete radiologic response in lymph nodes and extralymphatic sites with target nodes/nodal masses regressing to ≤ 1.5 centimeters (cm) in longest transverse diameter (LDi) and no extralymphatic sites of disease; absence of non-measured lesion; organ enlargement regressing to normal; no new lesions; normal bone marrow by morphology, if indeterminate, IHC negative.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
CRR, as Determined by the Investigator Using Lugano Response Criteria for Malignant Lymphoma	58.3 percentage of participants Interval 36.64 to 77.89	76.9 percentage of participants Interval 56.35 to 91.03

SECONDARY outcome

Timeframe: AEs were reported up to 28 days after the last dose (up to approximately 7 months), and SAEs were reported up to 6 months after the last dose of study treatment (up to approximately 1 year)

Population: The safety analysis population consisted of all randomized participants who received at least one dose of study drug, with participants grouped according to treatment received.

AE: any untoward medical occurrence in a subject administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. New disease, exacerbation of existing disease, recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test associated with symptoms or leading to a change in study/concomitant treatment or discontinuation from study drug as well as events related to protocol-mandated interventions are considered AEs. SAEs: any event that met any of these criteria: fatal, life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, medically significant or required intervention to prevent any of the outcomes listed here.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	24 Participants	26 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	11 Participants	8 Participants

SECONDARY outcome

Timeframe: Up to 24 hours after the last dose of study treatment (up to approximately 24 weeks)

Population: The safety analysis population consisted of all randomized participants who received at least one dose of study drug, with participants grouped according to treatment received.

Adverse events occurring within 24 hours after administration of rituximab (rituximab IV or rituximab SC) and considered related to the study drug, were considered as ARRs. ARRs could present with one or more of the following symptoms: allergic reaction, arthralgia, bronchospasm, chills, cough, dizziness, dyspnoea, headache, hypertension, hypotension, myalgia, nausea, pruritus, pyrexia, rash, tachycardia, urticaria, vomiting.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Number of Participants With Rituximab Administration-related Reactions (ARRs)	6 Participants	7 Participants

SECONDARY outcome

Timeframe: From baseline up to 6 months after the last dose of study treatment (up to approximately 1 year)

Population: The immunogenicity analysis population consisted of all participants with at least one anti-drug antibody (ADA) assessment. Participants were grouped according to treatment received or, if no treatment was received prior to study discontinuation, according to treatment assigned.

Reported here is the number of participants who had a positive ADA assay result at baseline or post-baseline. The post-baseline results are divided in treatment-enhanced ADAs and treatment-induced ADAs. Treatment-enhanced ADAs are participants with a positive ADA result at baseline who had one or more post-baseline titer results that was at least 0.60 titer unit greater than the baseline titer result. Treatment-induced ADAs include participants with negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=24 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP n=26 Participants Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Number of Participants Positive for Anti-drug Antibodies (ADAs) to Rituximab Post-baseline: Treatment-enhanced	1 Participants	0 Participants
Number of Participants Positive for Anti-drug Antibodies (ADAs) to Rituximab Baseline	2 Participants	1 Participants
Number of Participants Positive for Anti-drug Antibodies (ADAs) to Rituximab Post-baseline: Treatment-induced	1 Participants	1 Participants

SECONDARY outcome

Timeframe: From baseline up to 6 months after the last dose of study treatment (up to approximately 1 year)

Population: The immunogenicity analysis population consisted of all participants with at least one anti-rHuPH20 assessment. Participants were grouped according to treatment received or, if no treatment was received prior to study discontinuation, according to treatment assigned.

Reported here is the number of participants who had a positive anti-rHuPH20 antibody assay result at baseline or post-baseline. The post-baseline results are divided in treatment-enhanced anti-rHuPH20 antibodies and treatment-induced anti-rHuPH20 antibodies. Treatment-enhanced anti-rHuPH20 antibodies are participants with a positive anti-rHuPH20 antibody result at baseline who had one or more post-baseline titer results that was at least 0.60 titer unit greater than the baseline titer result. Treatment-induced anti-rHuPH20 antibodies include participants with negative or missing baseline anti-rHuPH20 antibody result(s) and at least one positive post-baseline anti-rHuPH20 antibody result.

Outcome measures

Outcome measures
Measure	Rituximab IV+CHOP n=26 Participants Participants received 8 cycles of intravenous (IV) rituximab in combination with 6 or 8 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy administered every 3 weeks.	Rituximab SC+CHOP Participants received 1 cycle of IV plus 7 cycles of subcutaneous (SC) rituximab in combination with 6 or 8 cycles of CHOP chemotherapy administered every 3 weeks.
Number of Participants Positive for Anti-rHuPH20 Antibodies Baseline	2 Participants	—
Number of Participants Positive for Anti-rHuPH20 Antibodies Post-baseline: Treatment-enhanced	1 Participants	—
Number of Participants Positive for Anti-rHuPH20 Antibodies Post-baseline: Treatment-induced	1 Participants	—

Adverse Events

Rituximab IV+CHOP

Serious events: 11 serious events

Other events: 24 other events

Deaths: 2 deaths

Rituximab SC+CHOP

Serious events: 8 serious events

Other events: 26 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER