RYBREVANT® (amivantamab-vmjw) HCP

Treatment with RYBREVANT^® was evaluated in the CHRYSALIS trial

CHRYSALIS is a multicenter, open-label, multicohort study that included 129 adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease progressed on or after platinum-based chemotherapy.¹

Efficacy was evaluated in 81 patients with locally advanced or metastatic NSCLC who had EGFR exon 20 insertion mutations as determined by prospective local testing using tissue (94%) and/or plasma (6%) samples, whose disease had progressed on or after platinum-based chemotherapy.¹

Efficacy was evaluated by ORR according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by Blinded Independent Central Review (BICR). An additional efficacy outcome measure was duration of response (DOR) by BICR.¹

Baseline Characteristics for the Efficacy Population (n=81)¹
Median age	62 years (range: 42-84 years)
Female / Male	59% / 41%
Asian	49%
White	37%
Black	2.5%
Baseline body weight <80kg	74%
Adenocarcinoma	95%
Prior Immunotherapy	46%
ECOG performance status 1	67%
Median number of prior therapies	2 (range: 1-7 therapies)
Never smoked	53%
Metastatic disease	100%
Previous treatment for brain metastases	22%

Baseline Characteristics for the Efficacy Population (n=81)¹

Median age

62 years (range: 42-84 years)

Female / Male

59% / 41%

Asian

49%

White

37%

Black

2.5%

Baseline body weight <80kg

74%

Adenocarcinoma

95%

Prior Immunotherapy

46%

ECOG performance status 1

67%

Median number of prior therapies

2 (range: 1-7 therapies)

Never smoked

53%

Metastatic disease

100%

Previous treatment for brain metastases

22%

RYBREVANT^® demonstrated durable responses in the CHRYSALIS trial

ORR in patients with EGFR exon 20 insertion mutations (n=81)¹

*According to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as evaluated by Blinded Independent Central Review (BICR).

The median DOR was 11.1 months (95% CI: 6.9, NE)^1†

63% of patients who responded had a DOR of ≥6 months

^†Based on Kaplan-Meier estimates.

BICR, Blinded Independent Central Review; CI, confidence interval; CR, complete response; DOR, duration of response; EGFR, epidermal growth factor receptor; ILD, Interstitial Lung Disease; NE, not estimable; ORR, overall response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions

RYBREVANT^® can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting.

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT^®. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT^® due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT^® as recommended. Administer RYBREVANT^® via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT^® infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT^® based on severity.

Interstitial Lung Disease/Pneumonitis

RYBREVANT^® can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT^®, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT^® due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT^® in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions

RYBREVANT^® can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT^®, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT^® was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT^®.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT^®. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin.

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce or permanently discontinue RYBREVANT^® based on severity.

Ocular Toxicity

RYBREVANT^® can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT^®. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT^® based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal models, RYBREVANT^® can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT^®.

Adverse Reactions

The most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).

Please read full Prescribing Information for RYBREVANT^®.

cp-213274v2

Study Results

Treatment with RYBREVANT^® was evaluated in the CHRYSALIS trial

CHRYSALIS is a multicenter, open-label, multicohort study that included 129 adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease progressed on or after platinum-based chemotherapy.¹

RYBREVANT^® demonstrated durable responses in the CHRYSALIS trial

**ORR in patients with EGFR exon 20 insertion mutations (n=81)¹**

You are leaving the RYBREVANT^® website

Study Results

Treatment with RYBREVANT® was evaluated in the CHRYSALIS trial

CHRYSALIS is a multicenter, open-label, multicohort study that included 129 adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease progressed on or after platinum-based chemotherapy.1

RYBREVANT® demonstrated durable responses in the CHRYSALIS trial

ORR in patients with EGFR exon 20 insertion mutations (n=81)1

You are leaving the RYBREVANT® website

Treatment with RYBREVANT^® was evaluated in the CHRYSALIS trial

CHRYSALIS is a multicenter, open-label, multicohort study that included 129 adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease progressed on or after platinum-based chemotherapy.¹

RYBREVANT^® demonstrated durable responses in the CHRYSALIS trial

**ORR in patients with EGFR exon 20 insertion mutations (n=81)¹**

You are leaving the RYBREVANT^® website