Drug Trials Snapshots: ANKTIVA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 ANKTIVA Prescribing Information for all 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).
ANKTIVA (nogapendekin alfa inbakicept-pmnl)
ank-tee’-vah
Altor BioScience, LLC, an indirect wholly-owned subsidiary of ImmunityBio, Inc.
Original Approval date: April 22, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
ANKTIVA is a drug to activate the immune system (the body system that helps fight disease) used together with another drug called Bacillus Calmette-Guerin (BCG) to treat a subtype of non-muscle invasive bladder cancer (NMIBC), called carcinoma in situ (CIS). It is used in patients for whom BCG treatment was not effective in treating their bladder cancer. This means that the disease either did not improve on treatment or recurred following treatment with BCG.
How is this drug used?
ANKTIVA is a liquid that is mixed with BCG and placed into the bladder using a catheter. The treatment stays in the bladder for about two hours, then the catheter is removed, and the patient is allowed to empty their bladder.
ANKTIVA with BCG is given once a week for six weeks. If there is still evidence of cancer at Month 3, ANKTIVA with BCG may be given once a week for another six weeks. After that, if there is complete response (CR; defined as no evidence of cancer), ANKTIVA with BCG is given once a week for three weeks at Months 4, 7, 10, 13, and 19 (for a total of 15 additional treatments). If there is an ongoing CR at Month 25 and later, additional ANKTIVA with BCG may be given once a week for three weeks at Months 25, 31, and 37 (for a maximum of nine additional treatments).
Who participated in the clinical trials?
The FDA approved ANKTIVA based on evidence from one clinical trial of 88 patients with a specific type of bladder cancer called BCG-unresponsive, high-risk, NMIBC with CIS with or without Ta/T1 papillary disease. The trial was conducted at 22 sites in the United States. There were additional patients included to assess safety who did not meet the FDA criteria for BCG-unresponsive disease required to be considered for response.
The same trial was used to assess efficacy and safety.
How were the trials designed?
The side effects of ANKTIVA with BCG were evaluated in one clinical trial of 88 adults with BCG-unresponsive, high-risk, NMIBC with CIS with or without papillary (Ta/T1) disease following transurethral resection. Efficacy was evaluated in a subset of 77 patients that the FDA considered evaluable for response. All patients received ANKTIVA with BCG. The efficacy of ANKTIVA with BCG was evaluated by measuring whether there was no evidence of disease (CR) when a patient was evaluated during treatment and how long there was no evidence of disease.
How were the trials designed?
The safety and efficacy of ANKTIVA with BCG was established in an open-label, single-arm, multicenter clinical trial. Patients with NMIBC with CIS who did not have a CR or have recurrent disease following adequate treatment with BCG within 12 months were enrolled in the study. All patients with papillary disease had undergone surgery to remove the cancer that could be removed. Residual CIS disease that could not be removed or otherwise destroyed was permitted in the trial. None of the patients had bladder cancer that had entered the muscle or other areas of the body.
Patients received ANKTIVA with BCG weekly during the first six weeks and then once a week every three weeks at 4, 7, 10, 13, and 19 months (for a total of 15 doses) for patients with no or low-grade disease. Patients with evidence of disease at three months could receive weekly treatments for an additional six weeks. For patients with no evidence of disease at Month 25 and later, additional doses may be administered once a week for three weeks at Months 25, 31, and 37 for a maximum of nine additional doses. Tumors were examined every three months for up to two years. The major measures of treatment success were no evidence of disease (CR at any time) and duration of response (how long CR continued).
DEMOGRAPHICS SNAPSHOT
Figure 2 summarizes how many patients by sex were in the trial used to evaluate the side effects of ANKTIVA with BCG.
Figure 2. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by race were in the trial used to evaluate the side effects of ANKTIVA with BCG.
Figure 3. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by age were in the trial used to evaluate the side effects of ANKTIVA with BCG.
Figure 4. Baseline Demographics by Age
Source: Adapted from FDA Review
There were no Hispanic patients in the trial.
Who participated in the trials?
Table 1. Baseline Demographics of Patients in the Clinical Trial, Safety Population
| Demographic Parameters | ANKTIVA + BCG |
|---|---|
| N=88 | |
| Sex, n (%) | |
| Male | 77 (87.5) |
| Female | 11 (12.5) |
| Age, years | |
| Mean (SD) | 72.6 (9) |
| Median (min, max) | 73 (50, 91) |
| Age group, years, n (%) | |
| <65 | 14 (16) |
| ≥65 | 74 (84) |
| Race, n (%) | |
| White | 79 (90) |
| Black or African American | 6 (7) |
| Asian | 1 (1) |
| American Indian or Alaska Native | 1 (1) |
| Unknown | 1 (1) |
| Ethnicity, n (%) | |
| Hispanic or Latino | 0 (0) |
| Not Hispanic or Latino | 88 (100) |
| Disease, n (%) | |
| CIS | 62 (70) |
| CIS + papillary | 26 (30) |
Source: Adapted from FDA Review
Abbreviations: BCG, Bacillus Calmette-Guerin; CIS, carcinoma in situ; SD, standard deviation
What are the benefits of this drug?
In one trial, 62% of patients who received ANKTIVA with BCG showed CR (no evidence of bladder cancer) at any time during the trial, and 58% of those patients had CR for over one year. Forty percent of patients with a CR at any time during the trial had a CR for over two years.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy results are shown in Table 2.
Table 2. Efficacy Results, Efficacy Population
| Parameter | ANKTIVA + BCG |
|---|---|
| N=77 | |
| Complete response rate, % (95% CI) | 62 (51, 73) |
| Duration of responsea, months | |
| Range | 0.0, 47.0+ |
| ≥12, n (%) | 28 (58) |
| ≥24, n (%) | 19 (40) |
Source: Adapted from FDA Review
+ Denotes ongoing response
a Based on 48 patients that achieved a complete response at any time; reflects period from the time complete response was achieved.
Abbreviations: BCG, Bacillus Calmette-Guerin; CI, confidence interval
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: Most patients in the clinical trial were male. The number of females in the trial was small; therefore, differences in how ANKTIVA worked among sexes could not be determined.
- Race: Most patients in the clinical trial were White. The number of patients of races other than White was small; therefore, differences in how ANKTIVA worked among races could not be determined.
- Age: Most patients in the clinical trial were older than 65 years of age. The number of patients younger than 65 years of age in the trial was small; therefore, differences in how ANKTIVA worked among age subgroups could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
CR rate at any time by subgroup is shown in Figure 5 and Table 3.
Figure 5. Complete Response at Any Time by Subgroup, CIS Patients, Efficacy Population
Source: Adapted from FDA Review
Abbreviations: BCG, Bacillus Calmette-Guerin; CI, confidence interval; CIS, carcinoma in situ; CR, complete response; CRR, complete response rate
Table 3. Complete Response Rate at Any Time by Subgroup, CIS Patients, Efficacy Population
| Complete Response | ||
|---|---|---|
| Subgroup | n/N (%) | 95% CI |
| Overall | 48/77 (62) | 51, 73 |
| Age, years | ||
| <65 | 9/13 (69) | 39, 91 |
| ≥65 | 39/64 (61) | 48, 73 |
| Sex | ||
| Male | 44/66 (67) | 54, 78 |
| Female | 4/11 (36) | 11, 69 |
| Race | ||
| White | 42/69 (61) | 48, 72 |
| Otherb | 5/7 (71) | 26, 96 |
| Baseline disease | ||
| CIS | 29/53 (55) | 40, 68 |
| CIS + papillary | 19/24 (79) | 58, 93 |
| Prior BCG doses | ||
| <12 | 11/14 (79) | 49, 95 |
| ≥12 | 37/63 (59) | 46, 71 |
Source: Adapted from FDA Review
a The 95% CIs were calculated using exact binomial method.
b Other includes: Black or African American (n=6), Asian (n=1), American Indian or Alaska Native (n=1), and unknown (n=1)
Abbreviations: BCG, Bacillus Calmette-Guerin; CI, confidence interval; CIS, carcinoma in situ
What are the possible side effects?
The most common side effects were increased creatinine (a measure of how well your kidneys filter waste from your blood), pain or burning when urinating, blood in urine, frequent daytime urination, immediate unstoppable urge to urinate, urinary tract infection, increased potassium levels in your blood, pain in the muscles, bones, ligaments, tendons, and nerves, chills, and fevers.
Other side effects include fatigue, nausea, bladder irritation, diarrhea, and the need to wake up at night to urinate.
Pain in the muscles, bones, ligaments, tendons, and nerves led some patients to stop taking ANKTIVA with BCG.
ANKTIVA with BCG treatment was interrupted in some patients because of urinary tract infection, pain or burning when urinating, blood in urine, and bladder irritation.
Delaying removal of the bladder can lead to the spread of cancer to the muscles of the bladder or other parts of the body, which can be fatal.
ANKTIVA with BCG may cause serious side effects including blood in urine.
What are the possible side effects (results of trials used to assess safety)?
Table 4 summarizes the adverse reactions in CIS patients.
Table 4. Adverse Reactions Occurring in ≥15% of Patients in CIS Patients, Safety Population
| Adverse Reaction | ANKTIVA + BCG, N=88 | |
|---|---|---|
| All Grades (%) | Grades 3 or 4 (%) | |
| Pain or burning when urinating | 32 | 0 |
| Blood in urinea | 32 | 3.4 |
| Frequent daytime urination | 27 | 0 |
| Immediate unstoppable urge to urinatea | 25 | 0 |
| Urinary tract infectiona | 24 | 2.3 |
| Pain in the muscles, bones, ligaments, tendons, and nervesa | 17 | 2.3 |
| Chills | 15 | 0 |
| Fever | 15 | 0 |
Source: ANKTIVA Prescribing Information
a Includes other related terms
Abbreviations: BCG, Bacillus Calmette-Guerin; CIS, carcinoma in situ
Clinically relevant adverse reactions in <15% of patients who received ANKTIVA with BCG included fatigue (14%), nausea (14%), bladder irritation (11%), diarrhea (9%), and the need to wake up at night to urinate (7%).
Table 5 summarizes the laboratory test abnormalities occurring in ≥15% of patients.
Table 5. Select Laboratory Test Abnormalities (≥15%) That Worsened From Baseline in Patients in CIS Patients, Safety Population
| Laboratory Abnormality | ANKTIVA + BCG, N=88 | |
|---|---|---|
| All Grades | Grades 3 or 4 | |
| (%) | (%) | |
| Increased creatinine | 76 | 0 |
| Increased potassium | 18 | 2 |
Source: ANKTIVA Prescribing Information
a The denominator used to calculate the rates was 88 based on the number of patients with a baseline value and at least one post-treatment value.
Abbreviations: BCG, Bacillus Calmette-Guerin; CIS, carcinoma in situ
Were there any differences in side effects among sex, race, and age?
- Sex: The majority of patients in the clinical trial were male. Differences in side effects between males and females could not be determined.
- Race: The majority of patients in the clinical trial were White. Differences in side effects among races could not be determined.
- Age: The majority of patients in the clinical trial were older than 65 years of age. Differences in side effects between patients younger and older than 65 years of age could not be determined.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 6. Subgroup Analysis of Treatment-Emergent Adverse Events – All Grades, Safety Population
| Demographic Subgroup | ANKTIVA + BCG |
|---|---|
| N=88 | |
| n/Ns (%) | |
| Sex | |
| Male | 73/77 (95) |
| Female | 11/11 (100) |
| Age group, years | |
| <65 | 14/14 (100) |
| ≥65 | 70/74 (95) |
| Racea | |
| White | 75/79 (95) |
| Otherb | 8/8 (100) |
Source: Adapted from FDA Review
a One patient’s race was unknown, and the patient was excluded from the racial subgroup analysis.
b Other includes 6 Black or African American patients, 1 Asian patient, and 1 American Indian or Alaska Native patient. There were so few patients that were not White that they were combined into one group to make comparison easier.
Abbreviations: BCG, Bacillus Calmette-Guerin; n, number of patients meeting criteria; N, number of patients in treatment arm; Ns, total number of patients for each specific subgroup and were assigned to that specific arm
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.