Drug Trials Snapshot: RYBREVANT

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 RYBREVANT 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).

RYBREVANT (amivantamab-vmjw)
(RYE–breh–vant)
Janssen Biotech, Inc.
Approval date: May 21, 2021

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

RYBREVANT is a prescription medicine use to treat adults with non-small cell lung cancer (NSCLC) that:

• has spread to other parts of the body (metastatic) or cannot be removed by surgery, and
• has a certain abnormal epidermal growth factor receptor (EGFR) mutation (exon 20 gene mutations) and
• whose disease has worsened while on or after chemotherapy that contains platinum.

How is this drug used?

RYBREVANT is given by a healthcare provider by intravenous infusion into the vein. The healthcare provider determines the dose based on the patient’s body weight. The healthcare provider will decide the time between doses as well as how many treatments will be given.

Who participated in the clinical trials?

The FDA approved RYBREVANT based on evidence from one clinical trial of (NCT02609776) 129 adult patients with advanced or metastatic non-small cell lung cancer (NSCLC) that has “EGFR” exon 20 gene mutations and whose disease has worsened while on or after chemotherapy that contains platinum. The trial was conducted at 53 sites in the United States, South Korea, Taiwan, Japan, Great Britain, France, Spain, Canada, China, and Australia.

All 129 patients that provided the data for the assessment of side effects of RYBREVANT (safety population) are presented below. 81 patients provided data for the assessment of the benefits of RYBREVANT (efficacy population) and they are presented in Table 1 The number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.

What are the benefits of this drug?

Forty percent of 81 patients with previously treated NSCLC experienced complete or partial shrinkage of their tumors. Shrinkage lasted at least 6 months for 63% of those patients.

RYBREVANT 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: Efficacy Results

Efficacy Parameter	RYBREVANT Prior Platinum-based chemotherapy treated (n=81)
Overall Response Rate (ORR), % (95% CI)	40 (29, 51)
Complete Response, %	3.7
Partial Response, %	36
Duration of Response (DOR)
Median, months (95% CI)	11.1 (6.9, NE)
Patients with DOR ≥ 6-months, %	63

NE=Not Estimable, CI=confidence interval.

RYBREVANT Prescribing Information

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

• Sex: RYBREVANT worked similarly in males and females.
• Race: RYBREVANT worked similarly in White and Asian patients. The number of patients of races other than White and Asian was small; therefore, differences in how RYBREVANT worked among all races could not be determined.
• Age: RYBREVANT worked similarly in patients below and above 65 years of age.

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

Table 2: Subgroup Analyses based on Overall Response Rate

Demographic Subgroup	Responders/n	ORR (95% CI)
Sex
Women	17/48	35 (22, 51)
Men	15/33	45 (28, 64)
Race
Asian	17/40	43 (27, 59)
White	13/30	43 (25, 63)
Black or African American	1/2	50 (1, 99)
Other	1/9	11 (0, 48)
Age
<65 years	21/48	44 (29, 59)
≥65 years	11/33	33 (18, 52)

FDA Review

What are the possible side effects?

RYBREVANT may cause serious side effects including infusion-related reactions, lung inflammation, skin problems, eye problems, and harm to an unborn baby.

The most common side effects of RYBREVANT are rash, infusion-related reactions, infected skin around the nail, muscle and joint pain, shortness of breath, nausea, feeling very tired, swelling of hands, ankles, feet, face, or all of your body, sores in the mouth, cough, constipation, vomiting, and changes in certain blood tests (for example, decreased albumin levels, increased glucose levels, increased liver enzymes).

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

Table 3: Adverse Reactions (≥ 10%) in patients who received RYBREVANT

	RYBREVANT (N-129)
Adverse Reactions	All Grades (%)	Grade 3 or 4 (%)
Skin disorders
Rasha	84	3.9
Pruritus	18	0
Dry skin	14	0
General disorders and administration-site conditions
Infusion related reaction	64	3.1
Fatigueb	33	2.3
Edemac	27	0.8
Pyrexia	13	0
Infections
Paronychia	50	3.1
Pneumoniad	10	0.8
Musculoskeletal disorders
Musculoskeletal paine	47	0
Respiratory, thoracic, and mediastinal disorders
Dyspneaf	37	2.3
Coughg	25	0
Gastrointestinal disorders
Nausea	36	0
Stomatitish	26	0.8
Constipation	23	0
Vomiting	22	0
Diarrhea	16	3.1
Abdominal Paini	11	0.8
Vascular disorders
Hemorrhagej	19	0
Metabolism and nutrition disorders
Decreased appetite	15	0
Nervous system disorders
Peripheral neuropathyk	13	0
Dizziness	12	0.8
Headachel	10	0.8

^a Rash: acne, dermatitis, dermatitis acneiform, eczema, eczema asteatotic, palmar-plantar erythrodysesthesia syndrome, perineal rash, rash, rash erythematous, rash maculo-papular, rash papular, rash vesicular, skin exfoliation, toxic epidermal necrolysis
^b Fatigue: asthenia, fatigue
^c Edema: eyelid edema, face edema, generalized edema, lip edema, edema, edema peripheral, periorbital edema, peripheral swelling
^d Pneumonia: atypical pneumonia, lower respiratory tract infection, pneumonia, pneumonia aspiration, and pulmonary sepsis
^e Musculoskeletal pain: arthralgia, arthritis, back pain, bone pain, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, spinal pain
^f Dyspnea: dyspnea, dyspnea exertional
^g Cough: cough, productive cough, upper airway cough syndrome
^h Stomatitis: aphthous ulcer, cheilitis, glossitis, mouth ulceration, mucosal inflammation, pharyngeal inflammation, stomatitis
ⁱ Abdominal pain: abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and epigastric discomfort
^j Hemorrhage: epistaxis, gingival bleeding, hematuria, hemoptysis, hemorrhage, mouth hemorrhage, mucosal hemorrhage
^k Peripheral neuropathy: hypoesthesia, neuralgia, paresthesia, peripheral sensory neuropathy
^l Headache: headache, migraine

RYBREVANT Prescribing Information

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 males and females
• Race: The occurrence of side effects was similar in White and Asian patients. The number of patients of races other than White and Asian was small; therefore, differences in the occurrence of side effects among all races could not be determined.
• 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 4: Subgroup Analysis of Adverse Events by Sex

	Women (N=79) n (%)	Men (N=50) n (%)
Patients with TEAEs	79 (100)	49 (98)
Patients with TEAEs Grade ≥3	37 (47)	16 (32)
Patients with Serious TEAEs	26 (33)	13 (26)

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Table 5: Subgroup Analysis of Adverse Events by Race

	Asian (N=71) n (%)	Non-Asian (N=48) n (%)
Patients with TEAEs	70 (99)	48 (100)
Patients with TEAEs Grade ≥3	22 (31)	24 (50)
Patients with Serious TEAEs	19 (27)	15 (31)

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Table 6: Subgroup Analysis of Adverse Events by Age

	< 65 years (N=76) n (%)	≥ 65 years (N=53) n (%)
Patients with TEAEs	76 (100)	52 (98)
Patients with TEAEs Grade ≥3	27 (36)	26 (49)
Patients with Serious TEAEs	15 (20)	24 (45)

TEAE=treatment-emergent adverse event
Adapted from FDA Review

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Demographics Snapshot

Figure 1 summarizes how many men and women were enrolled in the clinical trial used to evaluate the safety of RYBREVANT.

Figure 1. Baseline Demographics by Sex (Safety Population)

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

Figure 2. Baseline Demographics by Race (Safety Population)

Figure 3. Baseline Demographics by Age (Safety Population)

Table 7. Demographics of Patients in the Clinical Trial (efficacy population)

Demographic variable	RYBREVANT N=81
Sex, n (%)
Men	33 (41)
Women	48 (59)
Race, n (%)
Asian	40 (49)
White	30 (37)
Black or African American	2 (2.5)
Unknown	9 (11)
Age (years)
Median	62
Minimum, Maximum	(42, 84)
Age category, n (%)
<65 years	48 (59)
≥65 to < 75 years	26 (32)
≥75 years	7 (9)
Ethnicity, n(%)
Hispanic or Latino	3 (3.7)
Not Hispanic or Latino	68 (84)
Unknown	10 (12)

Table 8. Demographics of Patients in the Clinical Trial (safety population)

Demographic variable	RYBREVANT N=129
Sex, n (%)
Men	50 (39)
Women	79 (61)
Race, n (%)
Asian	71 (55)
White	45 (35)
Black or African American	3 (2.3)
Unknown	10 (8)
Age (years)
Median	62
Minimum, Maximum	(36, 84)
Age category, n (%)
<65 years	76 (59)
≥65 to < 75 years	42 (33)
≥75 years	11 (9)
Ethnicity, n(%)
Hispanic or Latino	4 (3.1)
Not Hispanic or Latino	114 (88)
Unknown	11 (9)

How were the trials designed?

The benefit and side effects of RYBREVANT for advanced or metastatic NSCLC with “EGFR” exon 20 gene mutations and whose disease has worsened while on or after treatment with platinum-based chemotherapy were evaluated in one clinical trial.

Depending upon the patient’s body weight, RYBREVANT was administered weekly for 4 weeks then every 2 weeks thereafter until either cancer progression or intolerable side effects occurred at a dose of 1050 mg if the patient’s body weight was less than 80 kg, or a dose of 1400 mg if the patient’s body weight was greater than or equal to 80 kg.

The benefit of RYBREVANT was evaluated by measuring the percentage of patients who achieved complete or partial shrinkage of their tumors (overall response rate) and by measuring the duration of that benefit (duration of response).

How were the trials designed?

There was one multicenter, non-randomized, open-label, multi-cohort trial that provided data to evaluate the safety and efficacy of RYBREVANT in adult patients with advanced or metastatic non-small cell lung cancer that has EGFR exon 20 gene mutations and whose disease has worsened while on or after treatment with platinum-based chemotherapy.

Patients received RYBREVANT (dose based on body weight) until unacceptable toxicity or disease progression. The major efficacy outcome measure for the cohort was overall response rate and duration of response as determined by blinded independent review committee according to RECIST v1.1.

Safety assessment was done on all patients who received at least one dose at the recommended dose(s) of RYBREVANT.

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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