(Amivantamab-Vmjw) NCCN Compendium Communication

RYBREVANTTM (amivantamab-vmjw) NCCN Compendium Communication – May 2021

Name: Cindy Toso, PharmD Company/Organization: Janssen Biotech, Inc. Address: 850 Ridgeview Drive Horsham, PA 19044 Phone: 215-325-4244 Email: [email protected] Date of request: May 24, 2021 NCCN Guidelines® Panel: Non-Small Cell Lung Cancer

Dear NCCN,

As follow-up to our Janssen Biotech, Inc. submission on April 27, 2021, I respectfully request the NCCN Guidelines® Non-Small Cell Lung Cancer Panel review the enclosed FDA approved labeling for RYBREVANTTM (amivantamab-vmjw).1

Please note that this submission (Inquiry #02218774) is a replacement to our previous submissions on May 24, 2021 (02218161) and May 21, 2021 (Inquiry #02206315).

Specific Changes: We request the inclusion of a new compendium monograph for amivantamab-vmjw and updates to the NCCN Guidelines® that include amivantamab-vmjw as a Category 1 targeted therapy for advanced or metastatic NSCLC with EGFRex20 insertion mutations, as well as inclusion of molecular testing for EGFRex20 insertion mutation within the biomarker testing algorithms. Specifically in the NCCN Guidelines® Non- Small Cell Lung Cancer, Version 4.2021:

• Systemic Therapy for Advanced or Metastatic Disease (NSCL-18-22) o Biomarker Testing Results, add a new row for EGFR Exon 20 Insertion Mutation (NSCL-19) and o Add a new EGFR Activating Mutation algorithm specific to EGFR Exon 20 insertion mutations • Targeted Therapy or Immunotherapy for Advanced or Metastatic Disease (NSCL-J) o Add a new sub-heading for “EGFR Exon 20 Insertion Mutation,” bullet “Subsequent therapy,” sub-bullet “amivantamab-vmjw”

FDA Clearance: The FDA approved RYBREVANT (amivantamab-vmjw) on May 21, 20212 for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum- based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. Information on FDA-approved tests is available at: http://www.fda.gov/Companion Diagnostics.1 Amivantamab received Breakthrough Therapy Designation from the FDA in March 2020 for this population.3

Rationale: Among uncommon EGFR mutations in NSCLC, EGFRex20 insertion is the most prevalent type of mutation and constitutes the third most common type of EGFR mutation in NSCLC overall (after exon 19 deletions and L858R point mutation in exon 21).4,5 EGFRex20 insertion mutations are often underdetected by conventional PCR testing;6,7 thus, diagnostic molecular profiling, as with next generation sequencing (NGS) technology,8-10 is important for early identification and appropriate characterization of patients.6,7 Most EGFRex20 insertion mutations in NSCLC have been associated with insensitivity or resistance to currently available small-molecule EGFR TKIs and are associated with poor prognosis (93% increased risk of progression or death and a 5-year overall survival of 8% with EGFREx20 insertion compared to common EGFR mutations);11 therefore, this represents an area of high unmet medical need.11-15 Amivantamab has been evaluated in this setting and demonstrates clinical efficacy in patients with EGFRex20 insertion mutations who have progressive disease following platinum-based chemotherapy as summarized in the CHRYSALIS study oral presentation.16

REFERENCES

1. RYBREVANT (amivantamab-vmjw) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT- pi.pdf.

2. PR Newswire. FDA approves first targeted therapy for subset of non-small cell lung cancer; https://www.prnewswire.com/news-releases/fda-approves-first-targeted-therapy-for-subset-of-non-small- cell-lung-cancer-301296998.html. May 21, 2021. Accessed May 21, 2021.

3. Janssen Announces U.S. FDA Breakthrough Therapy Designation Granted for JNJ-6372 for the Treatment of Non-Small Cell Lung Cancer. https://www.jnj.com/janssen-announces-u-s-fda-breakthrough-therapy- designationgranted-for-jnj-6372-for-the-treatment-of-non-small-cell-lung-cancer. Accessed May 21, 2021. 4. Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. Feb 2013;8(2):179-184. 5. Wang F, Li C, Wu Q, Lu H. EGFR exon 20 insertion mutations in non-small cell lung cancer. Transl Cancer Res. 2020;9(4):2982-2991. 6. Riess JW, Gandar DR, Frampton GM, et al. Diverse EGFR Exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thorac Oncolo. 2018;13(10):1560- 1568. 10.1016/j.jtho.2018.06.019. 7. Bauml JM, Viteri S, Minchom A, et al. Underdiagnosis of EGFR Exon 20 insertion mutation variants: estimates from NGS-based real-world datasets. Oral presentation presented at: International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer Singapore (WCLC 2020); January 28-31, 2021; Worldwide Virtual Event. 8. FDANews. FDA grants EAP designation to Guardant’s NGS-based liquid biopsy. February 21, 2018. https://www.fdanews.com/articles/185711-fda-grants-eap-designation-to-guardants-ngs-based-liquid- biopsy. Accessed March 2021. 9. Guardant Health announces collaboration with Janssen to develop liquid biopsy companion diagnostic. July 08, 2020. https://www.globenewswire.com/news-release/2020/07/08/2059237/0/en/Guardant-Health- Announces-Collaboration-with-Janssen-to-Develop-Liquid-Biopsy-Companion-Diagnostic.html. Accessed March 2021. 10. Thermo Fisher Scientific signs agreement with Janssen to co-develop companion diagnostic for cancer [press release]. March 12, 2020. https://thermofisher.mediaroom.com/2020-03-12-Thermo-Fisher- Scientific-Signs-Agreement-with-Janssen-to-Co-Develop-Companion-Diagnostic-for-Cancer. Accessed March 2021. 11. Girard N, Bazhenova L, Minchom A, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Oral presentation presented at: International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer Singapore (WCLC 2020); January 28-31, 2021; Worldwide Virtual Event. 12. Vyse S, Huang PH. Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. Signal Transduct Target Ther. 2019;4:5. 13. Arcila ME, Nafa K, Chaft JE, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013;12(2):220-229. 14. Yasuda H, Park E, Yun C-H, et al. Structural, biochemical and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer. Sci Transl Med. 2013;5(216):216ra177. 15. Yun J, Lee S-H, Kim S-Y, et al. Antitumor activity of amivantamab (JNJ-61186372), an EGFR-cMet bispecific antibody, in diverse models of EGFR Exon 20 insertion-driven NSCLC [published online ahead of print May 15, 2020]. Cancer Discov. doi: 10.1158/2159-8290.CD-20-0116. 16. Sabari JK, Shu CA, Park K, et al. Amivantamab in post-platinum EGFR exon 20 insertion mutant non- small cell lung cancer. Oral presentation presented at: International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer Singapore (WCLC 2020); January 28-31, 2021; Worldwide Virtual Event.