Drug Trials Snapshots: UKONIQ
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the UKONIQ Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
UKONIQ (umbralisib)
You-KON-ik
TG Therapeutics, Inc.
Approval date: February 5, 2021
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
UKONIQ is a drug used to treat adult patients with marginal zone lymphoma (MZL) when the disease has come back, or did not respond to treatment, and who have received at least one certain type of prior treatment.
Marginal zone lymphoma is a form of blood cancer.
How is this drug used?
UKONIQ is taken as a 200 mg tablet. Patients take 4 tablets (800 mg) once a day with food.
What are the benefits of this drug?
In a clinical trial with 69 patients with marginal zone lymphoma, 49% had a complete or partial shrinkage of their tumors (response).
UKONIQ was approved under FDA’s accelerated approval program, which provides earlier patient access to a promising new drug while the company continues to conduct clinical trials to confirm that the drug works well.
What are the benefits of this drug?
The table below summarizes efficacy results established on the basis of Overall Response Rate (ORR).
Table 1. Overall Response Rate (ORR) and Duration of Response (DOR) in Patients with Relapsed Marginal Zone Lymphoma
| Outcome per IRC | UKONIQ (N=69) |
|---|---|
| ORR, n (%)a | 34 (49) |
| 95% CI | 37.0, 61.6 |
| CR, n (%) | 11 (16) |
| PR, n (%) | 23 (33) |
| Duration of Response | |
| Median, months (95% CI)b | NR (9.3, NE) |
| Range, months | 0.0+, 21.8+ |
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
Source: UKONIQ Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: UKONIQ worked similarly in women and men.
- Race: The number of patients of races other than White was small; therefore, differences in how UKONIQ worked among races could not be determined.
- Age: UKONIQ worked similarly among patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes efficacy results by sex, race, and age. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Table 2. Demographic Subgroup Analysis of Overall Response Rate (ORR)
| Subgroup | Total | ORR, n (%) |
|---|---|---|
| Sex | ||
| Female | 36 | 17 (47) |
| Male | 33 | 17 (52) |
| Race | ||
| White | 57 | 26 (46) |
| Other* | 12 | 8 (67) |
| Age | ||
| < 65 years | 27 | 16 (59) |
| ≥ 65 years | 42 | 18 (43) |
Source: FDA Review
*Other includes Black, Asian, and Missing.
What are the possible side effects?
UKONIQ may cause serious side effects including infections, diarrhea or inflammation of the intestines, decreased level of infection-fighting white blood cells (neutropenia), abnormal liver blood tests and severe skin reactions. UKONIQ may also cause allergic reactions due to a certain inactive ingredient (FD&C Yellow #5) included in the tablets. In addition, taking UKONIQ can cause fetal harm and breastfeeding is not advised.
The most common side effects of UKONIQ are decreased kidney function (increased creatinine), diarrhea or inflammation of the intestines, fatigue, nausea, decreased level of infection-fighting white blood cells (neutropenia), abnormal liver blood tests, musculoskeletal pain, low levels of red blood cells (anemia), low levels of blood platelets (thrombocytopenia), upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.
What are the possible side effects?
The table below summarizes adverse reactions in adult patients with follicular lymphoma and marginal zone lymphoma who were treated with at least one dose of UKONIQ in combined clinical trials (safety population).
Table 3. Common Adverse Reactions (≥10% Incidence) in Patients With Follicular Lymphoma and Marginal Zone Lymphoma
| Adverse Reactions | UKONIQ N=221 |
|
|---|---|---|
| All Grades (%) |
Grade 3 or 4 (%) |
|
| Gastrointestinal Disorders | ||
| Diarrhea | 58 | 10 |
| Nausea | 38 | <1 |
| Vomiting | 21 | <1 |
| Abdominal paina | 19 | 3 |
| General Disorders and Administration Site Conditions | ||
| Fatigueb | 41 | 3 |
| Edemac | 14 | <1 |
| Pyrexia | 10 | 0 |
| Musculoskeletal and Connective Tissue Disorders | ||
| Musculoskeletal paind | 27 | 2 |
| Infections | ||
| Upper respiratory tract infectione | 21 | <1 |
| Metabolism and Nutrition Disorders | ||
| Decreased appetite | 19 | 2 |
| Skin and Subcutaneous Tissue Disorders | ||
| Rashf | 18 | 3 |
| Psychiatric Disorders | ||
| Insomnia | 14 | <1 |
Source: UKNOIQ Prescribing Information
aAbdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort
bFatigue includes fatigue, asthenia, lethargy
cEdema includes edema peripheral, face edema, pulmonary edema, fluid overload, generalized edema
dMusculoskeletal pain includes back pain, myalgia, pain in extremity, musculoskeletal pain, neck pain, spinal pain, musculoskeletal chest pain, musculoskeletal discomfort
eUpper respiratory tract infection includes upper respiratory tract infection, sinusitis, nasopharyngitis, rhinitis
fRash includes rash, rash maculo-papular, rash erythematous, rash pruritic, rash macular, exfoliative dermatitis
Table 4. Laboratory Adverse Reactions Reported (≥10%) in Patients With Follicular Lymphoma and Marginal Zone Lymphoma Treated with UKONIQ
| Laboratory Parameter | UKONIQ N=221 |
|
|---|---|---|
| All Gradesa (%) |
Grade 3 or 4a (%) |
|
| 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 |
Source: UKONIQ Prescribing Information
aLaboratory values were categorized using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 grading system.
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects were generally similar, in men and women. However, diarrhea, nausea, and vomiting were reported more frequently in women compared to men.
- Race: The number of patients of races other than White was small; therefore, differences in the occurrence of side effects among races could not be determined.
- Age: The occurrence of side effects was generally similar in patients younger and older than 65 years of age. However, 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 rate of infectious serious adverse reactions in patients 65 years of age or older (13%) compared to patients younger than 65 years of age (4%).
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes some of the common adverse reactions by sex and age subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Table 5. Subgroup Analysis of Common Adverse Reactions by Sex and Age
| Adverse reaction | Sex | Age | ||
|---|---|---|---|---|
| Men N=125 n (%) |
Women N=96 n (%) |
< 65 years N=98 n (%) |
≥ 65 years N=123 n (%) |
|
| Any Adverse Reaction | 125 (100) | 93 (97) | 96 (98) | 122 (99) |
| Diarrhea | 70 (56) | 59 (62) | 57 (58) | 72 (59) |
| Nausea | 41 (33) | 43 (45) | 36 (37) | 48 (39) |
| Vomiting | 21 (17) | 26 (27) | 19 (19) | 28 (23) |
Source: FDA Review
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the trials?
The FDA approved UKONIQ based on evidence from four clinical trials (Study TGR-1202-101, TGR 1202-202, UTX-TGR-205, and UTX-TGR-501) that included 221 adults with marginal zone lymphoma (37%) and follicular lymphoma (63%) who received at least one prior treatment for marginal zone lymphoma and two prior treatments for follicular lymphoma that did not work or was no longer working.
Trials were conducted at 85 sites in United States, Poland, United Kingdom, Spain, South Korea, Israel, Italy, Australia, and Slovakia.
The population that provided data for side effects of UKONIQ (safety population) is presented below. Demographics of the patients who provided data for evaluation of benefits (efficacy population) are presented in Table 8, under the MORE INFO section.
Figure 1 summarizes how many men and women were enrolled in the clinical trial used to evaluate the safety of UKONIQ (safety population).
Figure 1. Baseline Demographics by Sex (Safety Population)
Source: FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the clinical trials used to evaluate the safety of UKONIQ.
Figure 2. Baseline Demographics by Race (Safety Population)
Source: FDA Review
*Race was reported in 92% of patients. The pie chart and Table 6 reflect information on race in this group of patients.
Other includes American Indian or Alaska Native, Native Hawaiian or Pacific Islander and Missing.
Figure 3. Baseline Demographics by Age (Safety Population)
Adapted from FDA review and Prescribing Information
Who participated in the trials?
The tables below summarize the demographics of the safety and efficacy populations.
Table 6: Baseline Demographics of the Safety Population
| Demographic Characteristic | UKONIQ N = 221 n (%) |
|---|---|
| Sex, n (%) | |
| Men | 125 (57) |
| Women | 96 (43) |
| Race, n (%) | |
| White | 180 (81) |
| Black or African American | 12 (5) |
| Asian | 6 (2.7) |
| Othera | 5 (2.3) |
| Not reported | 18 (8) |
| Age (years) | |
| Median | 66 |
| Min, Max | 29, 88 |
| Age Group, n (%) | |
| < 65 years | 98 (44) |
| ≥65 years | 123 (56) |
| Ethnicity, n (%) | |
| Hispanic | 10 (4.5) |
| Non-Hispanic | 189 (86) |
| Not reported/unknown | 22 (10) |
| a Other includes American Indian or Alaska Native, Native Hawaiian or Pacific Islander and Missing | |
Table 7. Baseline Demographics of the Efficacy Population
| Demographic Characteristics | UKONIQ (N=69) n (%) |
|---|---|
| Age (years) | |
| Mean (SD) | 66 (10.0) |
| Median (minimum, maximum) | 67 (34, 88) |
| Age categories, n (%) | |
| <65 years | 27 (39) |
| ≥65 years | 42 (61) |
| Sex, n (%) | |
| Male | 33 (48) |
| Female | 36 (52) |
| Race, n (%) | |
| White | 57 (83) |
| Black or African American | 5 (7) |
| Asian | 2 (2.9) |
| Missing | 5 (7) |
| Region, n (%) | |
| US | 39 (57) |
| Non-US | 30 (43) |
| Weight (kg) | |
| Mean (SD) | 81.2 (20.97) |
| Median (minimum, maximum) | 80.0 (46.3, 165.0) |
| ECOG performance status, n (%) | |
| 0 | 38 (55) |
| 1 | 29 (42.0) |
| 2 | 2 (2.9) |
| MZL type, n (%) | |
| Extranodal | 38 (55) |
| Nodal | 20 (29) |
| Splenic | 11 (16) |
| Stage of disease at Screening, n (%) | |
| I | 4 (6) |
| II | 7 (10) |
| III | 12 (17) |
| IV | 44 (64) |
| Unknown | 2 (2.9) |
| Prior systemic therapy | |
| Median (minimum, maximum) | 2.0 (1, 6) |
| 1 | 34 (49) |
| 2 | 17 (25) |
| 3 | 8 (12) |
| >3 | 10 (14) |
| Anti-CD20 therapies, n (%) | 117 (100.0) |
| Anti-CD20 monotherapy only | 15 (22) |
| Anti-CD20 based chemoimmunotherapy | 52 (75) |
| Lenalidomide (mono or combo) | 4 (6) |
| Lenalidomide and anti-CD20 antibody | 3 (4.3) |
| Lenalidomide and rituximab | 3 (4.3) |
| BTK inhibitor | 2 (2.9) |
| Alkylating agent | 48 (70) |
Source: FDA Review
How were the trials designed?
The benefit and side effects of UKONIQ were evaluated in four clinical trials that included adult patients 29-88 years of age with follicular lymphoma and marginal zone lymphoma.
Trial 1 enrolled adult patients with follicular lymphoma after at least two prior treatments and marginal zone lymphoma after one prior treatment, that did not work or was no longer working. Patients received UKONIQ 800 mg orally once daily. Treatment continued until either disease worsened or patients experienced unacceptable toxicity. The benefit of UKONIQ was evaluated by measuring how many patients had complete or partial tumor shrinkage (response) and by how long that response lasted.
Trial 2 included patients with follicular lymphoma and marginal zone lymphoma whose disease has come back after at least two previous treatments. All patients received UKONIQ 800 mg oral daily until disease progression or unacceptable side effects. The benefit of UKONIQ was evaluated by measuring how many patients experienced complete or partial shrinkage of their tumors after treatment (response). Patients in Trial 2 were primarily evaluated for side effects for the purpose of this drug application.
Trial 3 enrolled patients with marginal zone lymphoma who had received one prior treatment. Patients received UKONIQ 800 mg orally once daily. The benefit of UKONIQ was evaluated by measuring how many patients had complete or partial tumor shrinkage (response) and how long that response lasted. Patients in Trial 3 were primarily evaluated for side effects for the purpose of this drug application.
Trial 4 was a long-term safety and efficacy extension study included patients with follicular lymphoma and marginal zone lymphoma who had completed treatment in Trial 2. Patients in Trial 4 were primarily evaluated for side effects.
How were the trials designed?
The safety and efficacy of UKONIQ were established in 4 clinical trials.
Efficacy of UKONIQ was evaluated in a single-arm cohort of Trial 1, an open-label, multi-center, multi-cohort trial including patients with relapsed or refractory marginal zone lymphoma after at least one prior systemic therapies, including an anti-CD20 containing regimen. 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.
Trial 2 was a first-in-human, open-label, Phase I study of UKONIQ administered as a single agent in patients with relapsed or refractory hematologic malignancies which included follicular lymphoma and marginal zone lymphoma. Patients included in this application received UKONIQ 800 mg orally once daily and were primarily evaluated for adverse events.
Trial 3 was an open-label, Phase II study of single agent UKONIQ in patients with non follicular indolent lymphomas that were relapsed or refractory following at least 1 prior standard therapy regimen. Patients with marginal zone lymphoma who received UKONIQ 800 mg orally daily were included in the safety evaluation of this application.
Trial 4 was an open-label, long-term safety and efficacy extension study for patients who completed treatment in parent studies including trial 2 and received UKONIQ 800 mg daily. Patients were primarily evaluated for adverse events for this application.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
PRESCRIBING INFORMATION