Study Evaluating Inotuzumab Ozogamicin (CMC-544) In Indolent Non-Hodgkins Lymphoma

CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (less than or equal to \[≤\]1.5 cm in their greatest transverse diameter \[GTD\] for nodes more than \[\>\]1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the sum of the product diameters (SPD) of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by greater than or equal to \[≥\]50% in the SPD or GTD (for single nodules). With exception of splenic and hepatic nodules, involvement of other organs was usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: Intent to treat (ITT) population: all participants who were enrolled into the study.

Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: Participants with Follicular NHL who responded.

Duration of response was measured from the first date of response until the first date that the objective progression of disease (PD) or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: Participants with Indolent NHL who responded.

Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.

Time frame: 6, 12 and 24 months

Population: ITT population (participants with NHL type defined as follicular).

Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.

Time frame: Any time up to 2 years after enrollment. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population (participants with NHL type defined as follicular).

Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.

Time frame: Any time up to 2 years after enrollment. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population.

Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to progression of disease or death from any cause. Events were defined as death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population (participants with NHL type defined as follicular).

Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to progression of disease or death from any cause. Events were defined as death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: 6, 12 and 24 months

Population: ITT population (participants with NHL type defined as follicular).

Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population.

Kaplan-Meier: a rule for calculating an estimate of survival. PFS was defined as time from enrollment to death from any cause without progression, progression during and after treatment, and initiation of all new anti-cancer treatments for the lymphoma. For participants with no event, censorship occurred at the date of last valid disease assessment. PD was defined in accordance with the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: 6, 12 and 24 months

Population: ITT population.

Kaplan-Meier: a rule for calculating an estimate of survival. OS was defined as the time from enrollment to death from any cause. For participants without death, censorship occurred at the date of last contact.

Time frame: 6, 12 and 24 months

Population: ITT population.

Triplicate 12-lead electrocardiogram (ECG) measurements were performed approximately 2 minutes apart. ECG assessments were pre-specified in the protocol to be time-matched with selected pharmacokinetic (PK) samples in order to conduct a concentration-QTc analysis. A study-specific QT correction factor was estimated using the un-averaged triplicate data and was used to calculate the study-specific corrected QT (QTcS). QTcS interval versus serum concentrations were modeled using a population analysis approach to identify potential effects of total calicheamicin exposure. Results for drug effects were based on the median Cmax for total calicheamicin across all participants: median Cmax was 61.3 ng/mL

Time frame: Cycle 1: pre-dose, 1 hour; Cycle 3 & 4: pre-dose, 1, 3, 48, 168 hours; Cycle 6 (if applicable): pre-dose; end of treatment: during clinic visit

Population: There were 80 participants in the analysis dataset, but time-matched PK-ECG data only existed for 73 participants (35 female).

Includes all TEAEs: any event that emerged after the first dose of the study treatment during the treatment period that was absent before administration of any study treatment, or worsened during the treatment period relative to the pre-treatment state.

Time frame: Protocol reporting period: from informed consent to at least 28 days after the last dose.

Population: Safety Population - includes all participants who received at least 1 dose of study medication. This population only excluded participants who never received any study medication.

CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population (participants with NHL type defined as follicular).

CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy. PR was defined as \>50% decrease in the SPD of up to 6 index lesions. No increase in size of other nodes, liver or spleen. Splenic and hepatic nodules must have regressed by ≥50% in the SPD or greatest transverse diameter (for single nodules). With exception of splenic and hepatic nodules, involvement of other organs was usually assessable and no measurable disease should be present. No progression of non-target disease or new lesions.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population (participants with NHL type defined as follicular).

CR was defined as complete disappearance of all target lesions and disease-related symptoms; all nodes must have decreased to normal (≤1.5 cm in their greatest transverse diameter for nodes \>1.5 cm before therapy) or ≤1 cm (short axis) in previously involved node; enlarged spleen prior to therapy must have regressed and be non-palpable; bone marrow lymphoma: infiltrate must have been cleared on repeat bone marrow aspirate and biopsy.

Time frame: Assessed for up to 2 years, including planned assessments every 8 to 12 weeks from first dose of study drug. Follow-up period may have been extended beyond 2 years due to dosing delays and allowed study visit windows.

Population: ITT population.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to the beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Maximum QTcF was categorized as less than or equal to (≤) 450 msec, \>450 msec to ≤480 msec, \>480 msec to ≤500 msec and \>500 msec. Participants are reported only once under the maximum QTcF interval observed at any of the time-points. Maximum increase from baseline was categorized as \<30 msec, ≥30 to \<60 msec (borderline) and ≥60 msec (prolonged) were summarized.

Time frame: Screening; Cycle 1: pre-dose & 1 hour; Cycles 3 and 4: pre-dose, 1, 3, 48, and 168 hours; Cycle 6: pre-dose; end of treatment: 28 to 56 days post-last dose.

Population: Safety Population

Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: 6, 12 and 24 months

Population: Participants with Follicular NHL who responded.

Duration of response was measured from the first date of response until the first date that the objective PD or symptomatic deterioration or initiation of new anticancer therapy for the lymphoma or death from any cause is documented. Participants without an event were censored at the date of the last valid tumor assessment. A valid tumor assessment visit was defined as the tumor assessment visit with overall response of CR, PR, stable disease (SD), or PD, but not 'Not Done' or 'Unknown'. PD was defined according to the International Response Criteria for NHL: 1) New lesion or increase by ≥50% of previously involved sites from nadir, 2) New lesion(s) \>1.5 cm (any axis); ≥50% increase in SPD of \>1 node; or ≥50% increase in longest diameter of previously identified node \>1 cm in short axis, 3) \>50% increase from nadir in the SPD of any previous lesions (splenic or hepatic) and 4) New or recurrent involvement in bone marrow.

Time frame: 6, 12 and 24 months

Population: Participants with Indolent NHL who responded.