Cancer Treatment Today

RYBREVANT (amivantamab-vmjw) is a low fucose, fully-human immunoglobulin G1 (IgG1)-based bispecific antibody with immune cell-directing activity that targets epidermal growth factor receptor (EGFR) mutations and mesenchymal-epithelial transition (MET) mutations and amplifications in non-small cell lung cancer (NSCLC). Nagasaka et al (2021) reported preliminary results from the RYBREVANT chemotherapy combination cohort from the CHRYSALIS study (NCT02609776) that included 5 treatment-naïve patients with EGFR Exon20ins mutations. In the analysis of the CHRYSALIS study, investigators assessed the efficacy and safety of RYBREVANT® in patients (n=114) with NSCLC and EGFR exon 20 insertion mutations, who had progressed on prior platinum-based chemotherapy, and were treated at the approved Phase 2 dose of 1050 mg (1400 mg for a patient weight of at least 80 kg).1 The primary endpoint was overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1* (RECIST v1.1).1 Additional endpoints included duration of response (DOR), clinical benefit rate, progression-free survival (PFS) and overall survival (OS).1

After a median follow-up of 19.2 months, the median OS with RYBREVANT® treatment was 23 months (95 percent Confidence Interval [CI], 18.5–29.5) with a two-year OS rate of 47 percent.1 The investigator-assessed ORR was 37 percent (95 percent CI, 28–46) with a median DOR of 12.5 months (95 percent CI, 6.9–19.3), and median PFS of 6.9 months (95 percent CI, 5.6-8.8).1 Across subgroups, treatment with RYBREVANT® resulted in consistent efficacy across post-platinum patients with EGFR exon 20 insertion mutations, including the elderly, regardless of prior therapies or response to prior platinum chemotherapy.1 Forty-eight patients (42 percent) had sustained clinical response measured by ORR on RYBREVANT® for at least 12 cycles.1 The median duration of treatment was 7.5 months and treatment is ongoing in 15 patients (13 percent) who have received RYBREVANT® for a median of 2.6 years. 16 cycles of therapy. RYBREVANT in combination with chemotherapy demonstrated a toxicity profile consistent with that observed with each therapy alone.
The PAPILLON study (NCT04538664)was of RYBREVANT in combination with chemotherapy (pemetrexed and carboplatin) vs chemotherapy alone (pemetrexed and carboplatin) in patients with untreated locally advanced or metastatic NSCLC and EGFR Exon20ins mutations.

The following clinical trials are ongoing:
RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:

As first-line therapy in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib, a novel third generation EGFR TKI, against osimertinib and against lazertinib alone in untreated advanced EGFR-mutated NSCLC.[viii]
The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of lazertinib, amivantamab and carboplatin-pemetrexed versus carboplatin-pemetrexed in patients with locally advanced or metastatic EGFR exon 19 deletion or exon 21 L858R substitution NSCLC after osimertinib failure.[ix]
The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating amivantamab in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.[x]
The Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed versus chemotherapy alone in patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations.[xi]
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.[xii]
The Phase 2 PALOMA-2 (NCT05498428) study assessing amivantamab in participants with advanced or metastatic solid tumors including EGFR-mutated NSCLC.[xiii]
The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab as compared to intravenous amivantamab in participants with EGFR-mutated advanced or metastatic NSCLC.[xiv]
The Phase 1/2 METalmark (NCT05488314) study assessing amivantamab and capmatinib combination therapy in unresectable metastatic NSCLC.[xv]

Moores SL, Chiu ML, Bushey BS, et al. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res. 2016;76(13):3942-3953.
Nagasaka M, Goto K, Gomez JE, et al. Amivantamab in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Poster presented at: International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer; September 8-14, 2021; Worldwide Virtual Event.
.Agrawal T, Artis E, Xie J, et al. PAPILLON: a randomized phase 3 study of amivantamab plus chemotherapy vs chemotherapy alone in EGFR exon 20ins NSCLC. Poster presented at: International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer Singapore (WCLC); January 28-31, 2021; Worldwide Virtual Event.
Garrido P., et al. Long-term efficacy, safety and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC. 2023 European Lung Cancer Congress. March 29, 2023.

[ii] Bazhenova, L., Minchom, A., Viteri, S., Bauml, J. M., Ou, S. I., Gadgeel, S. M., Trigo, J. M., Backenroth, D., Li, T., Londhe, A., Mahadevia, P., & Girard, N. (2021). Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung cancer (Amsterdam, Netherlands), 162, 154–161. https://doi.org/10.1016/j.lungcan.2021.10.020

RYBREVANTTM (amivantamab-vmjw) Receives FDA Approval as the First Targeted Treatment for Patients with Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations. Available at: https://www.janssen.com/rybrevant-amivantamab-vmjw-receives-fda-approval-first-targeted-treatment-patients-non-small-cell#_edn16. Accessed March 2023.
Janssen Announces New Data Supporting Safety and Efficacy of RYBREVANT® and Lazertinib Combination for Patients with Non-Small Cell Lung Cancer and EGFR Mutations. Available at: https://www.jnj.com/janssen-announces-new-data-supporting-safety-and-efficacy-of-rybrevant-and-lazertinib-combination-for-patients-with-non-small-cell-lung-cancer-and-egfr-mutations#_edn9. Accessed March 2023.