Johnson & Johnson : Janssen Submits Supplemental Biologics License Application to the U.S. Food and Drug Administration Seeking Approval of RYBREVANT® (amivantamab-vmjw) in Combination with Chemotherapy for the First-line Treatment of Patients with Locally Advanced or Metastatic EGFR Exon 20 Insertion Mutation-Positive Non Small Cell Lung Cancer

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Janssen Submits Supplemental Biologics License Application to the U.S. Food and Drug Administration Seeking Approval of RYBREVANT® (amivantamab-vmjw) in Combination with Chemotherapy for the First-line Treatment of Patients with Locally Advanced or Metastatic EGFR Exon 20 Insertion Mutation-Positive Non- Small Cell Lung Cancer

Application is supported by data from PAPILLON, the first randomized Phase 3 study to show clinically meaningful results in patients with NSCLC with EGFR exon 20 insertion mutations

RARITAN, New Jersey, August 25, 2023 - The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking the expanded approval of RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy (carboplatin-pemetrexed) for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. The sBLA is being reviewed by the FDA through the Real-Time Oncology Review (RTOR) program.*

"PAPILLON is the first randomized Phase 3 study in patients with NSCLC with EGFR exon 20 insertion mutations to show clinically meaningful results. This creates an opportunity to make a significant improvement to the standard of care for this patient population with high unmet medical need," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. "We look forward to working with the FDA through the RTOR pathway in pursuit of an approval for RYBREVANT plus chemotherapy as we simultaneously progress the development of this novel bispecific antibody in additional patient populations."

Following Breakthrough Therapy Designationfrom the U.S. FDA in 2020, RYBREVANT® received accelerated approvalin 2021 as the first fully-human, bispecific antibody for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations.2 The sBLA submission for RYBREVANT® is also intended to satisfy the regulatory requirements of the accelerated approval confirming the clinical benefit observed in the Phase 1 CHRYSALIS study.

The sBLA is supported by data from the Phase 3 PAPILLON (NCT04538664) clinical trial, a randomized, open-label study evaluating the efficacy and safety of RYBREVANT® in combination with chemotherapy as first-line treatment in patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.1,2 In July, Janssen announcedthe PAPILLON study met its primary endpoint with a statistically significant and clinically meaningful improvement in PFS (as measured by BICR) in patients receiving RYBREVANT® plus chemotherapy versus chemotherapy alone.1 The combination of RYBREVANT® and chemotherapy demonstrated a safety profile consistent with the safety profiles of the individual components.1

About PAPILLON

PAPILLON (NCT04538664) is a randomized, open-label Phase 3 study evaluating the efficacy and safety of RYBREVANT® in combination with chemotherapy, compared with chemotherapy alone, in newly diagnosed patients with advanced or metastatic NSCLC characterized by EGFR exon 20 insertion mutations.1 The primary endpoint of the study is PFS (using RECIST v1.1 guidelines**) as assessed by blinded independent central review (BICR). Secondary endpoints include overall response rate (ORR), PFS after first subsequent therapy, time to symptomatic progression and overall survival (OS).1 Patients who received chemotherapy alone were allowed to receive RYBREVANT® monotherapy in the second-line setting after confirmation of disease progression.1

About RYBREVANT®

RYBREVANT® (amivantamab-vmjw)receivedaccelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.2 This indication is approved under accelerated approval based on ORR and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT® has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer◊ prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.9†^

In addition to the Phase 3 PAPILLON study, RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:

• The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with lazertinib, a novel third generation EGFR TKI, versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or L858R substitution mutations.10
• The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.11
• The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in participants with advanced NSCLC.12
• The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.13
• The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous

(SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.14

• The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.15
• The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in participants with EGFR- mutated advanced or metastatic NSCLC.16
• The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.17
• The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.18
• The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion related reactions with RYBREVANT® in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.19

For more information, visit: https://www.RYBREVANT.com.

About Non-Small Cell Lung Cancer

Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to

85 percent of all lung cancer cases.20,21 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.22 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.23 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.22-28 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.29 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.30,31 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.32 Patients with EGFR exon 20 insertion mutations have a real-worldfive-year OS of 8 percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-worldfive-year OS of 19 percent.33

RYBREVANT® IMPORTANT SAFETY INFORMATION2

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