Drug Trials Snapshots: TIVDAK

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 TIVDAK 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).

TIVDAK (tisotumab vedotin-tftv)
(tiv-dak)
Seagen Inc.
Approval date: 9/20/2021

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

TIVDAK is a drug used in adults with cervical cancer. TIVDAK may be used when cancer has come back or spread to other parts of the body and chemotherapy did not work or stopped working.

How is this drug used?

TIVDAK is given into a vein in your arm (intravenous infusion) by a healthcare professional once every 3 weeks. It takes about 30 minutes to get the TIVDAK infusion.

Who participated in the clinical trials?

The FDA approved TIVDAK based on evidence from one clinical trial (NCT03438396) including 101 patients with cervical cancer that came back or had spread to other parts of the body. Chemotherapy didn’t work or had stopped working for the patients. The trial was conducted at 36 sites in Europe and the United States.

What are the benefits of this drug?

The trial measured the number of patients whose tumors completely or partially shrank with treatment with TIVDAK. In the trial, 24 of 101 patients (24%) treated with TIVDAK had tumors that completely or partially shrank, and that lasted an average of 8 months.

TIVDAK was approved under FDA’s accelerated approval program. This program lets patients take a promising new drug while the company continues clinical trials to confirm that the drug works well.

What are the benefits of this drug (results of trials used to assess efficacy)?

Table 1 below summarizes efficacy results for the clinical trial based on overall response rate (ORR) and duration of response assessed by independent review committee using Response Evaluation Criteria in Solid Tumors v1.1.

Endpoint	TIVDAK N=101
Confirmed ORR (95% CI)	24% (15.9, 33.3)
Complete response rate	7%
Partial response rate	17%
Duration of response
Median duration of response, months1 (95% CI)	8.3 (4.2, NR)

Source: TIVDAK Prescribing information
¹ Based on patients (n=24) with a response by IRC
Abbreviations: CI, confidence interval; IRC, independent review committee; NR, not reached; ORR, overall response rate

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: All included patients were female; therefore, sex differences could not be determined.
• Race: Almost all patients were White; therefore, race differences could not be determined.
• Age: No patient aged 65 and above had complete or partial shrinkage of their tumor.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table 2 shows ORR by subgroup. Sex and race were not included in the subgroup analysis, as all patients were female and almost all patients were White.

Table 2. Exploratory Efficacy Subgroup Analyses

Age	N	# Responders	Confirmed ORR (95% CI)
<65 years	88	24	27.3% (18.3, 37.8)
≥65 years	13	0	0% (0, 24.7)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; ORR, overall response rate

What are the possible side effects?

Eye problems are common with TIVDAK and can also be serious. TIVDAK can cause changes to the surface of your eye. These changes can lead to dry eyes, eye redness, eye irritation, damage to the cornea in the eye (corneal ulcers), blurred vision, and severe vision loss.

TIVDAK can cause serious side effects including nerve problems (peripheral neuropathy), bleeding (hemorrhage), lung problems, and harm to an unborn baby.

The most common side effects of TIVDAK include lower numbers of red blood cells and white blood cells, tiredness, upset stomach (nausea), hair loss (alopecia), nosebleed, changes in kidney function tests, dry eye, abnormal blood clotting test results, diarrhea, and rash.

What are the possible side effects (results of trials used to assess safety)?

Table 3 below summarizes common adverse reactions.

Table 3. Adverse Reactions (≥10%) in Patients Who Received TIVDAK

Adverse Reaction	TIVDAK N=101
	All Grades %	Grade 3 or 4 %
General
Fatigue1	50	7
Pyrexia	16	1
Pruritis	13	1
Gastrointestinal disorders
Nausea2	41	0
Diarrhea3	25	2
Constipation	23	2
Abdominal pain4	23	1
Vomiting	17	2
Nervous system disorders
Peripheral neuropathy5	39	7
Skin and subcutaneous tissue disorders
lopecia	39	0
Rash6	25	0
Vascular disorders
Epistaxis	39	0
Hemorrhage7	32	6
Eye disorders
Conjunctival adverse reactions8	37	0
Dry eye9	29	0
Corneal adverse reactions10	21	3
Periorbital adverse reactions11	16	0
Musculoskeletal and connective tissue disorders
Myalgia12	21	0
Arthralgia	16	0
Pain in extremity13	13	1
Metabolism and connective tissue disorders
Decreased appetite	16	1
Infections
Urinary tract infection14	14	2
Investigations
Weight decreased	12	0

Source: TIVDAK Prescribing Information
^1. Fatigue includes fatigue and asthenia
². Nausea includes nausea and retching
^3. Diarrhea includes diarrhea, gastroenteritis, and colitis
⁴. Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, abdominal distention and abdominal discomfort
^5. Peripheral neuropathy includes neuropathy peripheral, peripheral sensorimotor neuropathy, polyneuropathy, peripheral sensory neuropathy, paresthesia, hypoesthesia, burning sensation, neuralgia, sensory loss, peripheral motor neuropathy, muscular weakness, gait disturbance, and hyperesthesia
^6. Rash includes rash, rash maculo-papular, rash macular, dermatitis acneiform, dermatitis allergic, and erythema
^7. Hemorrhage includes vaginal hemorrhage, hematuria, rectal hemorrhage, cystitis hemorrhagic, lower gastrointestinal hemorrhage, urinary bladder hemorrhage, hematochezia, anal hemorrhage, gingival bleeding, post procedural hemorrhage, radiation associated with hemorrhage, metrorrhagia, large intestinal hemorrhage, paranasal sinus hemorrhage, and hemoptysis
^8. Conjunctival adverse reactions include conjunctivitis, conjunctival abrasion, conjunctival erosion, conjunctival hyperemia, conjunctival scar, noninfective conjunctivitis, ocular hyperemia, and conjunctival hemorrhage
^9. Dry eye includes dry eye and lacrimation increased
^10. Corneal adverse reactions include keratitis, punctate keratitis, ulcerative keratitis, corneal erosion, corneal scar, keratopathy, and corneal bleeding
^11. Periorbital adverse reactions include blepharitis, meibomianitis, eye pruritus, entropion, trichiasis, chalazion, and meibomian gland dysfunction
^12. Myalgia includes myalgia, musculoskeletal discomfort, and musculoskeletal pain
^13. Pain in extremity includes pain in extremity and limb discomfort
^14. Urinary tract infection includes urinary tract infection, urinary tract infection bacterial, and cystitis

Were there any differences in side effects among sex, race and age?

• Sex: Everyone in the trial was female; therefore, sex differences could not be determined.
• Race: Almost everyone in the trial was White; therefore, race differences could not be determined.
• Age: Patients aged 65 years or older were more likely to experience severe or serious side effects than patients under 65 years old.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Table 4 shows a summary of adverse reactions by age subgroup. Sex and race analyses were not conducted because all patients were female and almost all patients were White.

Table 4. Summary of Adverse Reactions by Age

Subjects With Any Event	<65y N=88 n (%)	≥65y N=13 n (%)
All ARs	88 (100)	13 (100)
Serious ARs	36 (40.9)	7 (53.8)
Grade ≥3 ARs	52 (59.1)	9 (69.2)

Source: Adapted from FDA Review
Abbreviations: AR, Adverse reaction

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes patients enrolled in the clinical trial by sex.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes patients enrolled in the clinical trial by race.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review

Figure 3 summarizes patients enrolled in the clinical trial by age.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes patients enrolled in the clinical trial by ethnicity.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

Who participated in the trials?

The demographic characteristics of the trial population are summarized in Table 5.

Table 5. Demographic Characteristics

Demographic	TIVDAK N=101
Age, years
Median	50.0
Min, max	31, 78
Age category, n (%)
<65 years	88 (87.1)
≥65 years	13 (12.9)
Region, n (%)
EU	86 (85.1)
US	15 (14.9)
Race, n (%)
White	96 (95.0)
Black or African American	1 (1.0)
Asian	2 (2.0)
Other	2 (2.0)
Ethnicity, n (%)
Hispanic or Latino	6 (5.9)
Not Hispanic or Latino	95 (94.1)

Source: Adapted from FDA Review
Abbreviations: EU, European Union; US, United States

How were the trials designed?

TIVDAK was approved based on one clinical trial. The trial enrolled 101 adults with cervical cancer whose disease came back or had spread to other parts of the body. Chemotherapy did not work or had stopped working for the patients in the trial before they got TIVDAK.

All patients got TIVDAK every 3 weeks until their cancer got worse (disease progression) or the side effects were too severe.

The trial measured how many patients treated with TIVDAK had cancer that completely or partially shrank and how long the shrinkage lasted. It also provided data on side effects.

How were the trials designed?

The FDA approved TIVDAK based on one clinical trial (NCT03438396). This was an open-label, multicenter, single-arm trial that enrolled patients with recurrent or metastatic cervical cancer. Patients had received one or two prior systemic treatment regimens for their cancer, including a platinum-based regimen, before starting the trial.

Patients received TIVDAK 2.0 mg/kg by intravenous infusion (IV) every 3 weeks until disease progression or unacceptable toxicity. Patients received tumor imaging assessments every 6 weeks for the first 7 months. After that, tumor imaging assessments occurred every 3 months.

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

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