Study Evaluating CMC-544 In B-Cell Non-Hodgkin's Lymphoma

MTD was defined as highest dose level for which no more than 1 participant in a dose cohort experienced dose limiting toxicity (DLT). DLT was defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to \[\>=\] 7 days), delayed recovery (less than or equal to \[\<=\] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 2 weeks.

Time frame: Baseline up to Day 28

Population: Safety population included all participants who received at least 1 dose of inotuzumab ozogamicin. This outcome measure was not planned to be analyzed in Part 2 of the study.

DLT was classified as per National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 3.0 and defined as any of the following events occurring during the first 21 days (or 28 days for participants treated every 4 weeks) days of study medication and considered at least possibly-related to study medication: any grade 3 or 4 non-hematologic toxicity except grade 3 alopecia, nausea, or vomiting, any grade 4 febrile neutropenia, any grade 4 thrombocytopenia or any bleeding episode requiring platelet transfusion, any grade 4 absolute neutrophil count (for a duration of greater than or equal to \[\>=\] 7 days), delayed recovery (less than or equal to \[\<=\] grade 1 or baseline) from a toxicity that delays the initiation of the next dose by more than 14 days.

Time frame: Baseline up to Day 28

Population: Safety population included all participants who received at least 1 dose of inotuzumab ozogamicin. Here number of participant analyzed (N) signifies participants evaluable for this outcome measure.

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE severity was defined to be the maximum toxicity grade of the treatment-emergent adverse events (TEAEs) experienced by the participants during the study. AE was assessed according to severity; Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening or disabling AE), Grade 5 (death related to AE). Participants with Grade 3 or higher grades TEAEs were reported.

Time frame: Baseline up to 42 days after last dose of study drug (up to Day 225)

Population: Safety population included all participants who received at least 1 dose of inotuzumab ozogamicin.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events (TEAE) are defined as any new event reported after first dose of study drug up to 42 days after last dose of study drug, or any event that is worse in severity than at any time during the baseline period. AEs included both SAEs and non-serious adverse events (non-SAEs).

Time frame: Baseline up to 42 days after last dose of study drug (up to Day 225)

Population: Safety population included all participants who received at least 1 dose of inotuzumab ozogamicin.

Duration of overall response was defined as the time from the date that measurement criteria were met for CR, CRu, or PR (whichever status was recorded first) until the first date that relapsed disease was objectively documented as per International Response Criteria for NHL, taking as reference for relapsed disease the smallest measurements recorded since the treatment started. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Population: Evaluable population was analyzed. DoR included evaluable participants who achieved CR, CRu, or PR. Here 'N' signifies number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of the study.

Participants with BOR=with complete response(CR),unconfirmed CR(CRu) or partial response (PR) as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical,radiographic sign of disease/related symptoms,normalization biochemical abnormalities related to NHL;if enlarged before therapy all lymph nodes,nodal masses,other organs regressed to normal size and spleen regressed in size,undetectable on physical exam,clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass \>1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by \>75% in product diameters and indeterminate bone marrow. PR:\>=50% decrease in sum of products of greatest diameters(SPD) of 6 largest dominant nodes/nodal masses,no increase in size of other nodes/spleen/liver, 50% decrease in SPD of splenic,hepatic nodules,involvement of other organs considered assessable,not measurable disease with exception of splenic,hepatic nodules.

Time frame: Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Population: Evaluable population was analyzed. Participants with diffuse or follicular lymphoma were analyzed. This outcome measure was not planned to be analyzed in Part 1 and Part 2 (Lead-in Cohort).

OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline up to Year 5

Population: Evaluable population: All participants who received at least 2 doses of study drug, had baseline tumor CT scan, and at least 1 post-baseline tumor assessment for anti-cancer clinical activity. Here 'N' represents number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of study.

Interval OS was based on Kaplan-Meier method. Survival was defined as the time period from the first dose of study drug until the date of death, censored at the participant's last contact date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline up to Year 5

Population: ITT population included all enrolled participants. Here 'N' signifies number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of the study.

PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per the International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Population: Evaluable population: All participants who received at least 2 doses of study drug, had baseline tumor computed tomography (CT) scan, and at least 1 post-baseline tumor assessment for anti-cancer clinical activity. Here 'N' represents number of participants evaluable for this outcome measure. This was not planned to be analyzed in Part 1 of study.

PFS was based on Kaplan-Meier estimates. PFS was defined as the time interval from the first dose of study medication until the first date on which relapsed disease, or progression (as per International Response Criteria for Non-Hodgkin Lymphoma) or death, was documented, censored at the last tumor evaluation date. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Population: Intent-to-treat (ITT) population included all enrolled participants. Here 'N' represents number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of the study.

Time to tumor progression was defined as the interval from the start of the treatment until the first date on which relapsed disease or progression is documented, censored at the last disease assessment. This outcome measure was analyzed in participants with follicular lymphoma or diffuse large B-cell lymphoma.

Time frame: Baseline, every 8 weeks up to Year 1, then every 12 weeks up to Year 2, and then every 6 months until tumor progression or death (up to Year 5)

Population: Evaluable population was analyzed. Here N signifies number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 and Part 2 (Lead-in Cohort) of the study.

Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or PR as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical, radiographic sign of disease/related symptoms, normalization biochemical abnormalities related to NHL; if enlarged before therapy all lymph nodes, nodal masses, other organs regressed to normal size and spleen regressed in size, undetectable on physical exam, clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass \>1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by \>75% in product diameters and indeterminate bone marrow. PR: \>=50% decrease in SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.

Time frame: Baseline up to 42 days after last dose (Day 225)

Population: Evaluable population: All participants who received at least 2 doses of study drug, had baseline tumor CT scan, and at least 1 post-baseline tumor assessment for anti-cancer clinical activity. Here 'N' represents number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of study.

Participants (having follicular or diffuse lymphoma) with objective response based assessment of CR, CRu or PR as per International Response Criteria for NHL. CR: Total disappearance of all detectable clinical, radiographic sign of disease/related symptoms, normalization biochemical abnormalities related to NHL; if enlarged before therapy all lymph nodes, nodal masses, other organs regressed to normal size and spleen regressed in size, undetectable on physical exam, clear bone marrow infiltrate. CRu: CR but allows for residual lymph node mass \>1.5 cm in greatest transverse diameter and all individual nodes previously merged were regressed by \>75% in product diameters and indeterminate bone marrow. PR: \>=50% decrease in SPD of 6 largest dominant nodes or nodal masses, no increase in size of other nodes, spleen or liver, 50% decrease in SPD of splenic, hepatic nodules, involvement of other organs considered assessable, not measurable disease with exception of splenic, hepatic nodules.

Time frame: Baseline up to 42 days after last dose of study drug (Day 225)

Population: ITT population included all enrolled participants. Here 'N' signifies number of participants evaluable for this outcome measure. This outcome measure was not planned to be analyzed in Part 1 of the study.