l benefit in a confirmatory trial(s). 1.2 follicular lymphoma ukoniq is indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma (fl) who have received at least three prior lines of systemic therapy. this indication is approved under accelerated approval based on overall response rate [see clinical studies ( 14.2 )] . continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

nfections occurred in 10% of 335 patients, with fatal infections occurring in <1%. the most frequent grade ≥3 infections included pneumonia, sepsis, and urinary tract infection. the median time to onset of grade ≥3 infection was 2.4 months (range: 1 day to 21 months) [see adverse reactions ( 6.1 )]. monitor for any new or worsening signs and symptoms of infection. for grade 3 or 4 infection, withhold ukoniq until infection has resolved. resume ukoniq at the same or a reduced dose [see dosage and administration ( 2.3 )]. provide prophylaxis for pneumocystis jirovecii pneumonia (pjp) during treatment with ukoniq [see dosage and administration ( 2.2 )] . withhold ukoniq in patients with suspected pjp of any grade and permanently discontinue in patients with confirmed pjp [see dosage and administration ( 2.2 )] . monitor for cytomegalovirus (cmv) infection during treatment with ukoniq in patients with a history of cmv infection. consider prophylactic antivirals during treatment with ukoniq to prevent cmv infection, including cmv reactivation [see dosage and administration ( 2.2 )]. for clinical cmv infection or viremia, withhold ukoniq until infection or viremia resolves. if ukoniq is resumed, administer the same or reduced dose and monitor patients for cmv reactivation by pcr or antigen test at least monthly [see dosage and administration ( 2.2 )] . 5.2 neutropenia serious neutropenia occurred in patients treated with ukoniq. grade 3 neutropenia developed in 9% of 335 patients and grade 4 neutropenia developed in 9% [see adverse reactions ( 6.1 )]. the median time to onset of grade 3 or 4 neutropenia was 45 days. monitor neutrophil counts at least every 2 weeks for the first 2 months of ukoniq and at least weekly in patients with neutrophil counts <1 ×10 9 /l (grade 3-4). consider supportive care as appropriate. withhold, reduce dose, or discontinue ukoniq depending on the severity and persistence of neutropenia [see dosage and administration ( 2.3 )]. 5.3 diarrhea or non-infectious colitis serious diarrhea or non-infectious colitis occurred in patients treated with ukoniq. any grade diarrhea or colitis occurred in 53% of 335 patients and grade 3 occurred in 9% [see adverse reactions ( 6.1 )]. the median time to onset for any grade diarrhea or colitis was 1 month (range: 1 day to 23 months), with 75% of cases occurring by 2.9 months. for patients with severe diarrhea (grade 3, i.e., > 6 stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, or peritoneal signs, withhold ukoniq until resolved and provide supportive care with antidiarrheals or enteric acting steroids as appropriate. upon resolution, resume ukoniq at a reduced dose. for recurrent grade 3 diarrhea or recurrent colitis of any grade, discontinue ukoniq. discontinue ukoniq for lifethreatening diarrhea or colitis [see dosage and administration ( 2.3 )]. 5.4 hepatotoxicity serious hepatotoxicity occurred in patients treated with ukoniq. grade 3 and 4 transaminase elevations (alt and/or ast) occurred in 8% and <1%, respectively, in 335 patients [see adverse reactions ( 6.1 )]. the median time to onset for grade 3 or higher transaminase elevations was 2.2 months (range: 15 days to 4.7 months). monitor hepatic function at baseline and during treatment with ukoniq. for alt/ast greater than 5 to less than 20 times uln, withhold ukoniq until return to less than 3 times uln, then resume at a reduced dose. for alt/ast elevation greater than 20 times uln, discontinue ukoniq [see dosage and administration ( 2.3 )] . 5.5 severe cutaneous reactions severe cutaneous reactions, including a fatal case of exfoliative dermatitis, occurred in patients treated with ukoniq. grade 3 cutaneous reactions occurred in 2% of 335 patients and included exfoliative dermatitis, erythema, and rash (primarily maculo-papular) [see adverse reactions ( 6.1 )] . the median time to onset of grade 3 or higher cutaneous reaction was 15 days (range: 9 days to 6.4 months). monitor patients for new or worsening cutaneous reactions. review all concomitant medications and discontinue any potentially contributing medications. withhold ukoniq for severe (grade 3) cutaneous reactions until resolution. monitor at least weekly until resolved. upon resolution, resume ukoniq at a reduced dose. discontinue ukoniq if severe cutaneous reaction does not improve, worsens, or recurs. discontinue ukoniq for life-threatening cutaneous reactions or sjs, ten, or dress of any grade [see dosage and administration ( 2.3 )]. provide supportive care as appropriate. 5.6 allergic reactions due to inactive ingredient fd&c yellow no. 5 ukoniq contains fd&c yellow no. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. although the overall incidence of fd&c yellow no. 5 (tartrazine) sensitivity in the general population is low, it is frequently seen in patients who also have aspirin hypersensitivity. 5.7 embryo-fetal toxicity based on findings in animals and its mechanism of action, ukoniq can cause fetal harm when administered to a pregnant woman. in animal reproduction studies, administration of umbralisib to pregnant mice during the period of organogenesis caused adverse developmental outcomes including embryo-fetal mortality and fetal malformations at maternal exposures comparable to those in patients at the recommended dose of 800 mg. advise pregnant women of the potential risk to a fetus. advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for one month after the last dose [see use in specific populations ( 8.1 , 8.3 )].

e warnings and precautions ( 5.1 )]. 2.3 dosage modifications for adverse reactions recommended dosage modifications of ukoniq for adverse reactions are presented in table 1 and the recommended dose reductions of ukoniq for adverse reactions are presented in table 2 . table 1: recommended dosage modifications of ukoniq for adverse reactions alt, alanine aminotransferase; anc, absolute neutrophil count; ast, aspartate aminotransferase; cmv, cytomegalovirus; pjp, pneumocystis jirovecii pneumonia; uln, upper limit of normal; sjs, stevens-johnson syndrome; ten, toxic epidermal necrolysis; dress, drug reaction with eosinophilia and systemic symptoms. a national cancer institute common terminology criteria for adverse events version 4.03. adverse reactions severity a dosage modification hematologic adverse reactions neutropenia [see warnings and precautions ( 5.2 )] anc 0.5 to 1 ×10 9 /l maintain ukoniq. if anc 0.5 to 1 × 10 9 /l recurs or is persistent, then withhold ukoniq until anc 1 × 10 9 /l or greater, then resume at same dose. anc less than 0.5 × 10 9 /l withhold ukoniq until anc 0.5 × 10 9 /l or greater, then resume at same dose. if recurrence, then resume at reduced dose. thrombocytopenia [see adverse reactions ( 6.1 )] platelet count 25 to less than 50 × 10 9 /l with bleeding or platelet count less than 25 × 10 9 /l withhold ukoniq until platelet count 25 × 10 9 /l or greater and resolution of bleeding (if applicable), then resume at same dose. if recurrence, withhold until resolution and then resume at reduced dose. nonhematologic adverse reactions infection, including opportunistic infection [see warnings and precautions ( 5.1 )] grade 3 or 4 withhold ukoniq until resolved, then resume at same or reduced dose. pjp for suspected pjp, withhold ukoniq until evaluated. for confirmed pjp, discontinue ukoniq. cmv infection or viremia withhold ukoniq until infection or viremia resolves, then resume at same or reduced dose. alt or ast elevation [see warnings and precautions ( 5.4 )] ast or alt greater than 5 to less than 20 times uln withhold ukoniq until return to less than 3 times uln, then resume at reduced dose. ast or alt greater than 20 times uln discontinue ukoniq. diarrhea or noninfectious colitis [see warnings and precautions ( 5.3 )] mild or moderate diarrhea (up to 6 stools per day over baseline) or asymptomatic (grade 1) colitis if persistent, withhold ukoniq until resolved, then resume at same or reduced dose. if recurrence, withhold until resolution and then resume at reduced dose. adverse reactions severity a dosage modification severe diarrhea (greater than 6 stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, peritoneal signs withhold ukoniq until resolved, then resume at reduced dose. for recurrent severe diarrhea or recurrent colitis of any grade, discontinue ukoniq. life-threatening discontinue ukoniq. severe cutaneous reactions [see warnings and precautions ( 5.5 )] severe withhold ukoniq until resolved, then resume at reduced dose or discontinue. if recurrence after re-challenge, discontinue ukoniq. life-threatening discontinue ukoniq. sjs, ten, dress (any grade) discontinue ukoniq. other adverse reactions [see adverse reactions ( 6.1 )] severe withhold ukoniq until resolved, then resume at the same or reduced dose. life-threatening discontinue ukoniq. table 2: recommended dose reductions of ukoniq for adverse reactions dose reduction dosage first 600 mg orally daily second 400 mg orally daily subsequent permanently discontinue ukoniq in patients unable to tolerate 400 mg orally daily

served in the clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in the general patient population. the pooled safety population described in warnings and precautions reflects exposure to ukoniq as monotherapy at a dosage of 800 mg orally once daily in 335 adults with hematologic malignancies in studies tgr-1202-101, tgr-1202-202, utx-tgr-205, and utx-tgr-501. among these 335 patients who received ukoniq, 52% were exposed for 6 months or longer and 30% were exposed for greater than one year. relapsed or refractory follicular lymphoma and marginal zone lymphoma the safety of ukoniq was evaluated in a pooled safety population that included 221 adults with marginal zone lymphoma (37%) and follicular lymphoma (63%) enrolled in three single-arm, open-label trials (study tgr-1202-101, tgr-1202-202, and utx-tgr-205) and one open-label extension trial (study utx-tgr-501) [see clinical studies ( 14.1 , 14.2 )] . these trials required hepatic transaminases ≤ 2.5 times upper limit of normal (uln), total bilirubin ≤ 1.5 times uln, and creatinine clearance ≥ 30 ml/min. no patients had prior exposure to a pi3k inhibitor. patients received ukoniq 800 mg orally once daily. among these 221 patients who received ukoniq, 60% were exposed for 6 months or longer and 34% were exposed for greater than one year. the median age was 66 years (range: 29 to 88 years), 43% were female, and 97% had an eastern cooperative oncology group (ecog) performance status of 0 to 1. race was reported in 92% of patients; of these patients, 89% were white, 6% were black, and 3% were asian. patients had a median of 2 prior therapies (range 1 to 10). serious adverse reactions occurred in 18% of patients who received ukoniq. serious adverse reactions that occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). fatal adverse reactions occurred in <1% of patients who received ukoniq, including exfoliative dermatitis. permanent discontinuation of ukoniq due to an adverse reaction occurred in 14% of patients. adverse reactions which resulted in permanent discontinuation of ukoniq in ≥5% of patients included diarrhea-colitis (6%) and transaminase elevation (5%). dose reductions of ukoniq due to an adverse reaction occurred in 11% of patients. adverse reactions which required dose reductions in ≥4% of patients included diarrhea-colitis (4%). dosage interruptions of ukoniq due to an adverse reaction occurred in 43% of patients. adverse reactions which required dosage interruption in ≥5% of patients included diarrhea-colitis (18%), transaminase elevation (7%), neutropenia (5%), vomiting (5%), and upper respiratory tract infection (5%). the most common (≥15%) adverse reactions, including laboratory abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash. table 3 provides the adverse reactions in the pooled safety population of 221 patients with marginal zone lymphoma and follicular lymphoma who received the recommended dosage. table 3: adverse reactions reported (≥10%) in patients with marginal zone lymphoma and follicular lymphoma who received ukoniq in pooled safety population a abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort b fatigue includes fatigue, asthenia, lethargy c edema includes edema peripheral, face edema, pulmonary edema, fluid overload, generalized edema d musculoskeletal pain includes back pain, myalgia, pain in extremity, musculoskeletal pain, neck pain, spinal pain, musculoskeletal chest pain, musculoskeletal discomfort e upper respiratory tract infection includes upper respiratory tract infection, sinusitis, nasopharyngitis, rhinitis f rash includes rash, rash maculo-papular, rash erythematous, rash pruritic, rash macular, exfoliative dermatitis adverse reactions ukoniq n=221 all grades (%) grade 3 or 4 (%) gastrointestinal disorders diarrhea 58 10 nausea 38 <1 vomiting 21 <1 abdominal pain a 19 3 general disorders and administration site conditions fatigue b 41 3 edema c 14 <1 pyrexia 10 0 musculoskeletal and connective tissue disorders musculoskeletal pain d 27 2 infections upper respiratory tract infection e 21 <1 metabolism and nutrition disorders decreased appetite 19 2 skin and subcutaneous tissue disorders rash f 18 3 psychiatric disorders insomnia 14 <1 clinically relevant adverse reactions in <10% of patients who received ukoniq included urinary tract infection (9%), dyspnea (7%), pneumonia (6%), sepsis (3%), colitis (2%), pneumonitis (<1%), and exfoliative dermatitis (<1%). table 4 provides the laboratory abnormalities in the pooled safety population of 221 patients with marginal zone lymphoma and follicular lymphoma who received the recommended dosage. table 4: select laboratory abnormalities (>20%) that worsened from baseline in patients with marginal zone lymphoma and follicular lymphoma who received ukoniq in pooled safety population a laboratory values were categorized using the national cancer institute common terminology criteria for adverse events (nci-ctcae) version 4.03 grading system. laboratory parameter ukoniq n=221 all grades a (%) grade 3 or 4 (%) hematologic neutrophil decreased 33 16 hemoglobin decreased 27 3 platelets decreased 26 4 chemistry creatinine increased 79 0 alanine aminotransferase increased 33 8 aspartate aminotransferase increased 32 7 potassium decreased 21 4

y in mice, pregnant animals were administered oral doses of umbralisib at 100, 200, and 400 mg/kg/day during the period of organogenesis. malformations were observed at doses of 200 mg/kg/day (cleft palate) and 400 mg/kg/day (cleft palate and nasopharyngeal fistula). additional findings occurred starting at the dose of 100 mg/kg/day and included folded retina, delayed ossification of sternebrae and vertebrae, increased resorptions, and increased post-implantation loss. the exposure (auc) at a dose of 100 mg/kg/day in mice is approximately equivalent to the human exposure at the recommended dose of 800 mg. in an embryo-fetal development study in rabbits, pregnant animals were administered oral doses of umbralisib at 30, 100, and 300 mg/kg/day during the period of organogenesis. administration at 300 mg/kg/day resulted in maternal toxicity (decreased food consumption and body weight) and reduced fetal weights. the exposure (auc) at 300 mg/kg/day in rabbits is approximately 0.03 times the exposure in human patients at the recommended dose of 800 mg. 8.2 lactation risk summary there are no data on the presence of umbralisib in human milk or the effects on the breastfed child or milk production. because of the potential for serious adverse reactions from umbralisib in the breastfed child, advise women not to breastfeed during treatment with ukoniq and for one month after the last dose. 8.3 females and males of reproductive potential ukoniq may cause fetal harm when administered to a pregnant woman [see use in specific populations ( 8.1 )]. pregnancy testing verify pregnancy status in females of reproductive potential prior to initiating ukoniq. contraception females advise females of reproductive potential to use effective contraception during treatment with ukoniq and for one month after the last dose. males advise males with female partners of reproductive potential to use effective contraception during treatment with ukoniq and for one month after the last dose. infertility males based on the findings from mice and dogs, ukoniq may impair male fertility [see nonclinical toxicology ( 13.1 )]. trend for reversibility was noted in dogs 30 days after the last dose. 8.4 pediatric use safety and effectiveness of ukoniq have not been established in pediatric patients. 8.5 geriatric use of the 221 patients with mzl or fl who received ukoniq in clinical studies, 56% of patients were 65 years of age and older, while 19% were 75 years of age and older. no overall differences in effectiveness or pharmacokinetics were observed between these patients and younger patients. in patients 65 years of age and older, 23% experienced serious adverse reactions compared to 12% in patients younger than 65 years of age. there was a higher incidence of infectious serious adverse reactions in patients 65 years of age or older (13%) compared to patients younger than 65 years of age (4%). 8.6 renal impairment no dose adjustment is recommended in patients with mild or moderate renal impairment (creatinine clearance [clcr] 30 to 89 ml/min estimated by cockcroft-gault equation) [see clinical pharmacology ( 12.3 )] . ukoniq has not been studied in patients with severe renal impairment ([clcr] < 30 ml/min). 8.7 hepatic impairment no dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [uln] and ast > uln or total bilirubin >1 to 1.5 × uln and any ast) [see clinical pharmacology ( 12.3 )] . ukoniq has not been studied in patients with moderate (total bilirubin > 1.5 to 3 × uln and any ast) or severe hepatic impairment (total bilirubin > 3 × uln and any ast).

0, 200, and 400 mg/kg/day during the period of organogenesis. malformations were observed at doses of 200 mg/kg/day (cleft palate) and 400 mg/kg/day (cleft palate and nasopharyngeal fistula). additional findings occurred starting at the dose of 100 mg/kg/day and included folded retina, delayed ossification of sternebrae and vertebrae, increased resorptions, and increased post-implantation loss. the exposure (auc) at a dose of 100 mg/kg/day in mice is approximately equivalent to the human exposure at the recommended dose of 800 mg. in an embryo-fetal development study in rabbits, pregnant animals were administered oral doses of umbralisib at 30, 100, and 300 mg/kg/day during the period of organogenesis. administration at 300 mg/kg/day resulted in maternal toxicity (decreased food consumption and body weight) and reduced fetal weights. the exposure (auc) at 300 mg/kg/day in rabbits is approximately 0.03 times the exposure in human patients at the recommended dose of 800 mg.

iac electrophysiology the effect of ukoniq on qt interval has not been fully characterized. 12.3 pharmacokinetics umbralisib exposures increased proportionally over a dose range of 200 mg to 1000 mg once daily (0.25 to 1.25 times the recommended dosage). a 6.4- and 3.8-fold accumulation of auc and c max of umbralisib, respectively, were observed at the recommended dosage. the mean (cv%) steady-state auc and c max were 141 μg*h/ml (46%) and 7.3 μg/ml (39%), respectively, at the recommended dosage. absorption the median time to reach peak plasma concentration (t max ) is approximately 4 hours. effect of food administration of a single dose of ukoniq with a high-fat, high calorie meal (approximately 917 calories with 171 calories from protein, 232 calories from carbohydrate, and 502 calories from fat) in healthy subjects increased auc and c max of umbralisib by 61% and 115%, respectively, relative to fasting conditions. distribution the mean (cv%) apparent central volume of distribution of umbralisib is 312 (185%) l. the plasma protein binding is ≥99.7% and was independent of concentration between 2 and 5 μm. mean blood-to-plasma ratio is 0.6. elimination the mean (cv%) apparent clearance of umbralisib is 15.5 (52%) l/h with effective half-life of 91 (42%) hours. metabolism umbralisib is metabolized by cyp2c9, cyp3a4, and cyp1a2 in vitro. excretion approximately 81% of the dose was recovered in feces (17% unchanged) and 3% in urine (0.02% unchanged) following a single radiolabeled dose of umbralisib 800 mg to healthy subjects. specific populations no clinically significant differences in the pharmacokinetics of umbralisib were observed based on age (18 to 87 years old), sex, race (white and black), body weight (44 to 165 kg), mild hepatic impairment (total bilirubin ≤ uln and ast > uln or total bilirubin >1 to 1.5 × uln and any ast), or mild and moderate renal impairment (clcr 30 to 89 ml/min, estimated by the cockcroft-gault equation). the effect of other race/ethnicity, severe renal impairment (clcr 15 to 29 ml/min) and dialysis, or moderate to severe hepatic impairment (total bilirubin ≤ uln and ast > uln or total bilirubin > uln and any ast) on umbralisib pharmacokinetics is unknown. drug interaction studies clinical studies no clinically significant differences in umbralisib pharmacokinetics were observed when used concomitantly with omeprazole, a proton pump inhibitor. coadministration of ukoniq with strong cyp3a4 inhibitors and inducers or moderate cyp2c9 inhibitors and inducers have not been studied. coadministration of ukoniq with sensitive substrates of cyp3a4, cyp2c8, cyp2c9 and cyp2c19, or p-gp substrates have not been fully characterized. in vitro studies cytochrome p450 (cyp) enzymes: umbralisib is a substrate of cyp1a2, cyp2c9, and cyp3a4, but is not a substrate of cyp2b6, cyp2c8, cyp2c19, cyp2d6, and ugt1a1. umbralisib inhibits cyp2c8, cyp2c9, cyp2c19, and cyp3a4, but does not inhibit cyp1a2, cyp2b6, and cyp2d6. umbralisib induces cyp3a4. transporter systems: umbralisib is not a substrate to p-gp, bcrp, oat1, oat3, oct2, oatp1b1, oatp1b3, mate1, and mate2-k. umbralisib inhibits p-gp.

ndent of concentration between 2 and 5 μm. mean blood-to-plasma ratio is 0.6. elimination the mean (cv%) apparent clearance of umbralisib is 15.5 (52%) l/h with effective half-life of 91 (42%) hours. metabolism umbralisib is metabolized by cyp2c9, cyp3a4, and cyp1a2 in vitro. excretion approximately 81% of the dose was recovered in feces (17% unchanged) and 3% in urine (0.02% unchanged) following a single radiolabeled dose of umbralisib 800 mg to healthy subjects. specific populations no clinically significant differences in the pharmacokinetics of umbralisib were observed based on age (18 to 87 years old), sex, race (white and black), body weight (44 to 165 kg), mild hepatic impairment (total bilirubin ≤ uln and ast > uln or total bilirubin >1 to 1.5 × uln and any ast), or mild and moderate renal impairment (clcr 30 to 89 ml/min, estimated by the cockcroft-gault equation). the effect of other race/ethnicity, severe renal impairment (clcr 15 to 29 ml/min) and dialysis, or moderate to severe hepatic impairment (total bilirubin ≤ uln and ast > uln or total bilirubin > uln and any ast) on umbralisib pharmacokinetics is unknown. drug interaction studies clinical studies no clinically significant differences in umbralisib pharmacokinetics were observed when used concomitantly with omeprazole, a proton pump inhibitor. coadministration of ukoniq with strong cyp3a4 inhibitors and inducers or moderate cyp2c9 inhibitors and inducers have not been studied. coadministration of ukoniq with sensitive substrates of cyp3a4, cyp2c8, cyp2c9 and cyp2c19, or p-gp substrates have not been fully characterized. in vitro studies cytochrome p450 (cyp) enzymes: umbralisib is a substrate of cyp1a2, cyp2c9, and cyp3a4, but is not a substrate of cyp2b6, cyp2c8, cyp2c19, cyp2d6, and ugt1a1. umbralisib inhibits cyp2c8, cyp2c9, cyp2c19, and cyp3a4, but does not inhibit cyp1a2, cyp2b6, and cyp2d6. umbralisib induces cyp3a4. transporter systems: umbralisib is not a substrate to p-gp, bcrp, oat1, oat3, oct2, oatp1b1, oatp1b3, mate1, and mate2-k. umbralisib inhibits p-gp.

station day 7 in females. adverse findings were observed at doses of 150 and 300 mg/kg/day and included decreased testicular and epididymis weights, decreased sperm mobility and counts, increased post-implantation loss, and increased resorption. the dose of 150 mg/kg results in an exposure approximately 1.3 times the human exposure (auc) at the recommended dose of 800 mg.

adverse findings were observed at doses of 150 and 300 mg/kg/day and included decreased testicular and epididymis weights, decreased sperm mobility and counts, increased post-implantation loss, and increased resorption. the dose of 150 mg/kg results in an exposure approximately 1.3 times the human exposure (auc) at the recommended dose of 800 mg.

ittee (irc) using criteria adopted from the international working group criteria for malignant lymphoma. the median follow-up time was 20.3 months (range: 15.0 to 28.7 months). efficacy results are shown in table 5 . table 5: efficacy results in patients with mzl (study 205) ci, confidence interval; cr, complete response; dor, duration of response; irc, independent review committee; orr, overall response rate; ne, not evaluable; nr, not reached; pr, partial response. a per irc according to revised international working group criteria b based on kaplan-meier estimation + denotes censored observation endpoint total (n=69) orr, n (%) a 34 (49) 95% ci 37.0, 61.6 cr, n (%) 11 (16) pr, n (%) 23 (33) dor median, months (95% ci) b nr (9.3, ne) range, months 0.0 + , 21.8 + the median time to response was 2.8 months (range: 1.8 to 21.2 months). overall response rates were 44.7%, 60.0%, and 45.5% for the 3 mzl sub-types (extranodal, nodal, and splenic, respectively). 14.2 follicular lymphoma the efficacy of ukoniq was evaluated in a single-arm cohort of study utx-tgr-205, an open-label, multi-center, multi-cohort trial (nct02793583). patients with relapsed or refractory fl were required to have received at least two prior systemic therapies, including an anti-cd20 monoclonal antibody and an alkylating agent. the trial excluded patients with grade 3b fl, large cell transformation, prior allogeneic transplant, history of cns lymphoma, and prior exposure to a pi3k inhibitor. patients received ukoniq 800 mg orally once daily until disease progression or unacceptable toxicity. a total of 117 patients with fl were enrolled in this cohort. the median age was 65 years (range: 29 to 87 years), 38% were female, 80% were white, 4% were black, 73% had stage iii-iv disease, 38% had bulky disease and 97% had a baseline ecog performance status of 0 to 1. patients had a median of 3 prior lines of therapy (range: 1 to 10), with 36% refractory to their last therapy. efficacy was based on overall response rate as assessed by an independent review committee (irc) using criteria adopted from the international working group criteria for malignant lymphoma. the median follow-up time was 20.1 months (range: 13.5 to 29.6 months). efficacy results are shown in table 6 . table 6: efficacy results in patients with relapsed or refractory fl (study 205) ci, confidence interval; cr, complete response; dor, duration of response; irc, independent review committee; orr, overall response rate; pr, partial response. a per irc according to revised international working group criteria b based on kaplan-meier estimation + denotes censored observation endpoint total (n=117) orr, n (%) a 50 (43) 95% ci 33.6, 52.2 cr, n (%) 4 (3.4) pr, n (%) 46 (39) dor median months (95% ci) b 11.1 (8.3, 16.4) range, months 0.0 + , 20.9 + the median time to response was 4.4 months (range: 2.2 to 15.5 months).

] . hepatotoxicity advise patients that ukoniq may cause significant elevations in liver enzymes and the need for periodic monitoring of liver tests. advise patients to report symptoms of liver dysfunction including jaundice (yellow eyes or yellow skin), abdominal pain, bruising, or bleeding [see warnings and precautions ( 5.4 )] . severe cutaneous reactions advise patients that ukoniq may cause a severe skin rash and to notify their healthcare provider immediately if they develop a new or worsening skin rash [see warnings and precautions ( 5.5 )]. embryo-fetal toxicity advise pregnant women and females of reproductive potential of the potential risk to a fetus. advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see warnings and precautions ( 5.7 ) , use in specific populations ( 8.1 , 8.3 )]. advise females of reproductive potential to use effective contraceptive during treatment with ukoniq and for one month after the last dose [see use in specific populations ( 8.3 )] . advise males with female partners of reproductive potential to use effective contraceptive during treatment with ukoniq and for one month after the last dose [see use in specific populations ( 8.3 )] . lactation advise women not to breastfeed during treatment with ukoniq and for one month after the last dose [see use in specific populations ( 8.2 )] . infertility advise males of reproductive potential that ukoniq may impair fertility [see use in specific populations ( 8.3 )]. allergic reactions due to inactive ingredient fd&c yellow no. 5 advise patients that ukoniq contains fd&c yellow no. 5 (tartrazine), which may cause allergic-type reactions in certain susceptible persons [see warnings and precautions ( 5.6 )]. administration inform patients to take ukoniq orally once daily at approximately the same time each day with food and how to make up a missed or vomited dose. advise patients to swallow tablets whole. advise patients not to crush, break, cut or chew tablets [see dosage and administration ( 2.1 )] . distributed by: tg therapeutics, inc. 343 thornall street, suite 740 edison, nj 08837 for patent information: https://www.tgtherapeutics.com/our-products/patent/ ukoniq™ is a trademark of tg therapeutics, inc. © tg therapeutics, inc. 2020