CR rate=percent of participants who achieved CR or complete response with incomplete marrow recovery(CRi).CR=no evidence of new disease,absolute lymphocyte count(ALC) in peripheral blood<4x10^9 per liter(/L),regression of nodal masses to normal size <1.5 centimeters(cm) in longest diameter(LD),normal spleen and liver size,no constitutional symptoms,cytological/pathological evaluation of bone marrow(BM) smear/biopsy must be at least normocellular for age without evidence for typical chronic lymphocytic leukemia(CLL)/small lymphocytic lymphoma(SLL) lymphocytes by morphological criteria,peripheral blood counts with absolute neutrophil count(ANC)≥1.5x10^9/L or platelet≥100x10^9/L or hemoglobin≥110 grams per liter(g/L) without red blood cell(RBC) transfusions,all without need for exogenous growth factors.CRi=all CR criteria but with persistent anemia,thrombocytopenia,or neutropenia or hypocellular BM that is related to prior/ongoing drug toxicity(and not to CLL/SLL).

ITT population for Phase 2 consisted of all participants who received at least one dose of each study drug (ublituximab, umbralisib, and venetoclax). Percentages were rounded off to the nearest decimal point.

ORR=percent of participants who achieve CR,CRi,partial response(PR) or PR with lymphocytosis(PR-L).CR=no evidence of new disease;ALC<4x10^9/L;regression of nodal masses to<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10^9/L,platelet≥100x10^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline(BL) in ALC(or decrease to<4x10^9/L) or sum of products(SPD) of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive progressive disease(PD);platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.

ITT population for Phase 2 consisted of all participants who received at least one dose of each study drug (ublituximab, umbralisib, and venetoclax). Percentages were rounded off to the nearest decimal point.

PFS was assessed in participants treated with U2-V compared with U2. PFS was defined as the interval between randomization and the date of definitive PD (as confirmed by the IRC) or death due to any cause, whichever occurs first. Participants who had no event (progression or death) were censored at the day of their last adequate disease assessment. PD= appearance of new nodes >1.5 cm in the LD, >50% increase in greatest diameter, new or recurrent hepatomegaly or splenomegaly, new unequivocal extra-nodal lesion, new non-target disease, ≥50% increase from the nadir in the sum of products of diameters (SPD) of target lesions, ≥50% increase in the LD of an individual node or extra-nodal mass, splenic/hepatic enlargement of ≥50% from nadir, unequivocal increase in the size of non-target disease, transformation to a more aggressive histology, decrease in platelet count or Hgb, >50% decrease from the highest on-study platelet count, >20 g/L decrease from the highest on-study Hgb.

ITT population for Phase 3 consisted of all participants who were randomized. Percentages were rounded off to the nearest decimal point.

The MRD negativity rate was defined as the percentage of participants who achieved MRD negative status post-baseline, defined as a quantitative detection of less than one CLL/SLL cell in 10000 leukocytes by flow cytometry (MRD level, 10^-4) in blood or bone marrow (BM). If a participant was determined to be MRD negative by peripheral blood, a bone marrow aspirate was obtained to assess MRD in the bone marrow. Participants who did not have an MRD assessment at any post-baseline visits were considered non-responders and were included in the denominator when calculating MRD negativity rate.

In Phase 2, ITT population consisted of all participants who received at least one dose of each study drug (ublituximab, umbralisib, and venetoclax); and in Phase 3, ITT population consisted of all participants who were randomized. Percentages were rounded off to the nearest decimal point.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product. An AE does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is any AE that occur after first dosing of study medication and through the end of the study or through 30 days after the last dose of study treatment, or is considered treatment-related regardless of the start date of the event, or is present before first dosing of study medication but worsens in intensity or the investigator subsequently considers treatment-related.

Safety population consisted of all participants who received at least one dose of any study drug (ublituximab, umbralisib, and venetoclax).

TTR was defined as the interval from enrollment to first documentation of CR, CRi, PR, or PR-L. TTR was analyzed via Kaplan-Meier method. CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to <1.5cm LD; normal spleen ,liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10^9/L, platelet≥100x10^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC (or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.

ITT population for Phase 2 consisted of all participants who received at least one dose of each study drug (ublituximab, umbralisib, and venetoclax). Only responders i.e., participants with ORR were assessed for this outcome measure.

DOR=interval from 1st documentation of CR,CRi,PR or PR-L to earlier of 1st documentation of definitive PD or death from any cause.CR=no evidence of new disease;ALC<4x10^9/L;regression of nodal masses to<1.5cm LD;normal spleen,liver size;no constitutional symptoms;cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age;ANC≥1.5x10^9/L,platelet≥100x10^9/L,Hb≥110g/L.CRi=CR criteria but with persistent anemia,thrombocytopenia,neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from BL in ALC(or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/Blymphoid;no target,splenic,liver,or non-target disease with worsening that meets criteria for definitive PD;platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria;not≥50% decrease from BL in ALC/decrease to<4x10^9/L.PD=evidence of new disease per protocol-specififed criteria.

ITT population for Phase 2 consisted of all participants who received at least one dose of each study drug (ublituximab, umbralisib, and venetoclax). Only responders i.e., participants with ORR were assessed for this outcome measure.

CR rate=percent of participants who achieved CR or CRi. CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to <1.5 cm LD; normal spleen, liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC ≥1.5x10^9/L, platelet ≥100x10^9/L, Hb ≥110g/L. CRi=CR criteria but with persistent anemia,thrombocytopenia,or neutropenia/hypocellular BM related to prior/ongoing drug toxicity. CR assessment was subject to independent confirmation by the IRC in participants enrolled to the Phase 3 stage of the study.

ITT population for Phase 3 consisted of all participants who were randomized. Percentages were rounded off to the nearest decimal point.

ORR=percent of participants who achieve CR, CRi, PR or PR-L.CR=no evidence of new disease; ALC<4x10^9/L; regression of nodal masses to<1.5cm LD; normal spleen and liver size; no constitutional symptoms; cytological/pathological evaluation of BM smear/biopsy must be at least normocellular for age; ANC≥1.5x10^9/L, platelet≥100x10^9/L, Hb≥110g/L. CRi=CR criteria but with persistent anemia, thrombocytopenia, or neutropenia/hypocellular BM related to prior/ongoing drug toxicity.PR=no evidence of new disease,meets≥2 criteria:≥50% decrease from baseline (BL) in ALC (or decrease to<4x10^9/L) or SPD of target nodal lesions or CLL/SLL marrow infiltrate/B-lymphoid; no target, splenic, liver, or non-target disease with worsening that meets criteria for definitive PD; platelet>100x10^9/L or Hb≥110g/L or ≥50% increase from BL in each.PR-L=PR criteria but not had ≥50% decrease from BL in ALC/decrease to<4x10^9/L.

ITT population for Phase 3 consisted of all participants who were randomized. Percentages were rounded off to the nearest decimal point.

Overall Survival (OS) was defined as the interval from randomization to death from any cause. OS data was censored at the last documented date that the participant was confirmed alive for participants who withdrew consent or were lost to follow-up prior to the end of the study, and for participants whose vital status in the study could not be determined.

ITT population for Phase 3 consisted of all participants who were randomized.