Drug Trials Snapshot: LYTGOBI

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 LYTGOBI 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).

LYTGOBI (futibatinib)
(light-GOH-bee)
Taiho Oncology Inc
Original Approval date: September 30, 2022

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

LYTGOBI is a drug used for the treatment of adults with a type of bile duct cancer (intrahepatic cholangiocarcinoma) that has spread to other parts of the body (metastatic) or cannot not be removed by surgery (unresectable). It should be used in patients who have been previously treated with chemotherapy and whose cancer has a certain type of abnormality in the FGFR2 gene.

How is this drug used?

LYTGOBI is a tablet that is taken by mouth once daily.

Who participated in the clinical trials?

The FDA approved LYTGOBI based on evidence from one clinical trial (NCT02052778) consisting of 103 patients with previously treated, locally advanced or metastatic intrahepatic bile duct cancer. The trial was conducted at 48 sites in the United States, Canada, Europe, and Asia.

How were the trials designed?

There was one trial that provided data for LYTGOBI approval. The trial enrolled adult patients with intrahepatic bile duct cancer (intrahepatic cholangiocarcinoma) who had been previously treated with chemotherapy for their advanced cancer and whose tumors had a certain type of abnormality in the FGFR2 gene.

Patients received LYTGOBI once daily by mouth until disease progression or the side effect became too toxic.

The trial measured the percentage of patients who achieved partial or complete shrinkage of their tumors and how long that shrinkage lasted (duration of response).

How were the trials designed?

There was one multi-center, open-label, single arm trial that provided data for approval of LYTGOBI. Enrolled patients were required to have locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma whose disease had progressed on or after at least one prior therapy, and an FGFR2 gene fusion or other rearrangement.

Patients received LYTGOBI 20 mg orally once daily until disease progression or unacceptable toxicity.

The major efficacy outcome measures were overall response rate and duration of response as determined by an independent review committee according to RECIST v1.1.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many male and female patients were enrolled in the clinical trial used to evaluate the safety and efficacy of LYTGOBI.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the safety and efficacy of LYTGOBI.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review

Figure 3 summarizes how many patients by age were in the trial used to evaluate the safety and efficacy of LYTGOBI.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes how many patients by ethnicity were in the trial used to evaluate the safety and efficacy of LYTGOBI.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

Who participated in the trials?

Demographic characteristics are summarized in Table 6.

Table 6. Demographic Characteristics

Demographic Parameter	LYTGOBI N=103 n (%)
Sex
Male	45 (44)
Female	58 (56)
Race
White	51 (49)
Asian	30 (29)
Black or African American	8 (8)
Native Hawaiian or Other Pacific Islander	1 (1)
Unknown	13 (13)
Age group, years
<65	80 (78)
≥65	23 (22)
Ethnicity
Hispanic or Latino	2 (2)
Not Hispanic or Latino	89 (86)
Unknown	12 (12)

Source: Adapted from FDA Review

What are the benefits of this drug?

In the trial, 42% (43 of 103) of patients treated with LYTGOBI experienced partial shrinkage of their tumors, also known as the overall response rate. Of these patients, 72% had tumor shrinkage lasting 6 months or longer and 14% had tumor shrinkage lasting 12 months or longer.

LYTGOBI 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 (results of trials used to assess efficacy)?

Table 1 summarizes the efficacy results based on the overall response rate and duration of response as determined by an independent review committee (IRC) according to guidelines for determining tumor shrinkage known as Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Table 1. Efficacy Results

Efficacy Parameter	LYTGOBI N=103
Overall response rate (95% CI)a	42% (32, 52)
Partial response, n (%)	43 (42)
Median duration of response, months (95% CI)b	9.7 (7.6, 17.1)
Duration of response ≥6 months, n (%)	31 (72)
Duration of response ≥12 months, n (%)	6 (14)

Source: LYTGOBI Prescribing Information
^a The 95% CI was calculated using Clopper–Pearson method.
^b The 95% CI was constructed based on a log-log transformed CI for the survival function.
Abbreviations: CI, confidence interval

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

• Sex: LYTGOBI worked similarly in females and males.
• Race: LYTGOBI worked similarly in White, Asian, and Black/African American participants.
• Age: The majority (78%) of patients were younger than 65 years of age and 22% of patients were 65 years of age and older. The observed response rate was larger for those age 65 years or older than for those younger than 65 years old.

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

Table 2 summarizes efficacy results by relevant demographic subgroups.

Table 2. Overall Response Rate as Assessed by IRC for Subgroups

Characteristics	N	Overall Response Rate (95% CI)
Sex
Male	45	38 (24, 54)
Female	58	45 (32, 59)
Race
White	51	41 (28, 56)
Asian	30	43 (26, 63)
Black or African American	8	50 (16, 84)
Other or unknown	14	36 (13, 65)
Age group, years
<65	80	35 (25, 47)
≥65	23	65 (43, 84)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; IRC, Independent review committee

What are the possible side effects?

LYTGOBI may cause serious side effects including detachment of retina (inner layer of the eye), increased phosphate levels in the blood, and harm to an unborn baby.

The most common side effects of LYTGOBI are nail toxicity, muscle and/or bone pain, constipation, and diarrhea.

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

Table 3 summarizes adverse reactions that occurred in ≥15% of patients treated with LYTGOBI.

Table 3. Adverse Reactions (≥15%) in Patients Receiving LYTGOBI

Adverse Reaction	LYTGOBI N=103
	All Gradesa (%)	Grade 3 (%)
Skin and subcutaneous tissue disorders
Nail toxicityb	47	1.9
Alopecia	34	0
Dry skin	29	0
Palmar-plantar erythrodysesthesia syndrome	21	4.9
Gastrointestinal disorders
Constipation	39	0
Diarrheac	39	1
Dry mouth	35	0
Stomatitisd	30	6
Abdominal paine	30	2.9
Nausea	24	1.9
Vomitingf	20	1
General disorders
Fatigueg	37	8
Metabolism and nutrition disorders
Decreased appetite	23	2.9
Musculoskeletal and connective tissue disorder
Musculoskeletal painh	43	3.9
Arthralgiai	25	0
Eye disorders
Dry eyej	25	1
Nervous system disorders
Dysgeusiak	25	0
Infections
Urinary tract infectionl	23	2.9
Investigations
Weight decreased	18	3.9

Source: LYTGOBI Prescribing Information
^a Graded per NCI CTCAE 4.03.
^b Includes nail toxicity, nail disorder, nail discoloration, nail dystrophy, nail hypertrophy, nail infection, nail pigmentation, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, and paronychia.
^c Includes diarrhea, colitis, and gastroenteritis.
^d Includes stomatitis, glossitis, mouth ulceration, mucosal inflammation, pharyngeal inflammation, and tongue ulceration.
^e Includes abdominal pain, abdominal discomfort, abdominal pain upper, gastrointestinal pain, and hepatic pain.
^f Includes vomiting and hematemesis.
^g Includes fatigue and asthenia.
^h Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, musculoskeletal stiffness, myalgia, neck pain, non-cardiac chest pain, pain in extremity, and spinal pain.
ⁱ Includes arthralgia and arthritis.
^j Includes dry eye, keratitis, lacrimation increased, photokeratitis, punctate keratitis, and ulcerative keratitis.
^k Includes dysgeusia, ageusia, and taste disorder.
^l Includes urinary tract infection, cystitis, and dysuria.
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events

Table 4. Select Laboratory Abnormalities (≥15%) Worsening From Baseline in Patients Receiving LYTGOBI

Laboratory Abnormalitya	LYTGOBI N=103
	All Gradesb (%)	Grades 3 or 4 (%)
Hematology
Decreased hemoglobin	52	6
Decreased lymphocytes	46	10
Decreased platelets	42	1
Decreased leukocytes	33	1.1
Decreased neutrophils	31	1.6
Chemistry
Increased phosphatec	97	39
Increased creatinined	58	0
Increased glucose	52	4.9
Increased calcium	51	1.2
Decreased sodium	51	15
Decreased phosphate	50	20
Increased alanine aminotransferase	50	7
Increased alkaline phosphatase	47	4.9
Increased aspartate aminotransferase	46	13
Decreased albumin	31	2.4
Increased creatine kinase	31	5
Increased bilirubin	28	0
Decreased glucose	25	0
Decreased potassium	22	2.1
Increased potassium	16	2
Coagulation
Increased activated partial thromboplastin time	36	8
Increased prothrombin international normalized ratio	25	0

Source: LYTGOBI Prescribing Information
^a Graded per NCI CTCAE 4.03.
^b Percentages are based on patients with data at both baseline and at least one post-baseline data value.
^c NCI CTCAE 4.03 does not define grades for increased phosphate. Laboratory value shift table categories were used to assess increased phosphorus levels (Grades ≥3 defined as >7 mg/dL).
^d Graded based on comparison to upper limit of normal.
Abbreviations: NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events

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

• Sex: The occurrence of side effects was similar in both the male and female patients.
• Race: All participants experienced side effects. The occurrence of grade 3 or 4 adverse events was similar in White and Asian participants. All Black or African American participants experienced a grade 3 or 4 adverse event.
• Age: The occurrence of side effects was similar in patients below and above 65 years of age.

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

Table 5 summarizes adverse reactions (side effects) by sex, race, and age.

Table 5. Summary of Adverse Events by Subgroup

Demographic Parameter	N	All Grades n (%)	Grade 3 or 4 n (%)
Sex
Male	45	45 (100)	33 (73)
Female	58	58 (100)	46 (79)
Race
White	51	51 (100)	37 (73)
Asian	30	30 (100)	24 (80)
Black or African American	8	8 (100)	8 (100)
Other or unknown	14	14 (100)	10 (71)
Age group, years
<65	80	80 (100)	63 (79)
≥65	23	23 (100)	16 (70)

Source: Adapted from FDA Review

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 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.

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