Rybrevant (amivantamab-vmjw)

After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.

This pharmacovigilance study systematically explored the cardiovascular adverse events of amivantamab and provided new safety signals based on past safety information. Early and intensified monitoring is crucial, and attention should be directed towards high-risk signals.

P1/2, N=117, Recruiting, Janssen Research & Development, LLC

P1/2 | "Clinical Trial Registration Number: NCT05488314"

P3 | "Clinical Trial Registration Number: NCT04487080"

P2, N=300, Recruiting, Janssen Research & Development, LLC | N=180 --> 300

P2, N=74, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting

The MARIPOSA trial was designed to study if the combination of amivantamab plus lazertinib in untreated epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients would provide improved progression-free survival. Here, we discuss the rationale for the study and the early results of MARIPOSA.

We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

NSCLC w/EGFRex19del & MET amp: durable intracranial + systemic response to amivantamab/osimertinib.

Consequently, their detection allows for the selection of emerging treatment options to significantly improve patients' outcomes in these particular subgroups of EGFR-mutated advanced non-small cell lung cancer (NSCLC). Specifically, this commentary is focused on the notable progress of the Phase 3 PAPILLON study that showed primary efficacy results from amivantamab, a bispecific antibody with specific binding and affinity to extracellular domains of EGFR and MET, plus chemotherapy in the first-line setting for EGFR exon 20 insertion-mutated advanced or metastatic NSCLC patients, as compared with chemotherapy alone, thus becoming the new standard of care in this group of patients.

P2, N=88, Not yet recruiting, SWOG Cancer Research Network | Initiation date: Feb 2024 --> May 2024

The costly price of amivantamab is one of the major reasons for the high cost of this combined treatment strategy. Therefore, it is imperative to take into account the high cost of amivantamab in the subsequent clinical application and strive to attain a relative equilibrium between its significant clinical benefit and economic encumbrance.

P2, N=62, Terminated, Janssen Pharmaceutical K.K. | Completed --> Terminated; Due to reconsideration of development strategy

There are three currently active sub-studies and one soon to be activated sub-study studying amivantamab-vmjw in MET amplification positive NSCLC (S1900J). Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC...One hundred seventy (7%) were submitted with the classification of "Other". The most common reasons included: no sub studies available, patient chose hospice, and patient transferred to different hospital.

Our data support the use of osimertinib in real-word settings and highlight the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice. It is yet to be determined if the use of evolving first-line EGFR inhibitor combination strategies (either platinum-doublet chemotherapy plus osimertinib or amivantamab plus lazertinib) will similarly translate from clinical trials to real-word settings.

P1/2, N=80, Recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2025 --> Aug 2026

P1, N=751, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2024 --> Jun 2025

This study provides a comprehensive longitudinal ctDNA analysis in patients with EGFR ex20ins mutant NSCLC who were treated with amivantamab. Our results suggested that the presence of ctDNA for EGFR ex20ins mutation and co-alteration with EGFR amplification at baseline might be related to the clinical outcomes of amivantamab.

P2, N=67, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Aug 2026

P1/2, N=225, Recruiting, Janssen Research & Development, LLC | Trial completion date: Mar 2026 --> Apr 2027 | Trial primary completion date: May 2024 --> Apr 2027

P2, N=180, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P=N/A, N=30, Recruiting, Groupe Francais De Pneumo-Cancerologie

Passaro et al.1 demonstrated in EGFR+ NSCLC post-1L osimertinib both "quad" (lazertinib [L] + amivantamab [A] + chemotherapy [CP]) and "triplet" (ACP) regimens achieved improved median progression-free survival over CP. Nonetheless, a high incidence of adverse events requiring dose modifications may limit adaptation of the triplet and quad MARIPOSA-2 regimens.

The PAPILLON trial showed that adding amivantamab to carboplatin-pemetrexed for advanced non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations is more effective than chemotherapy. Although safety concerns may arise, this study highlights the need for alternative therapeutic strategies beyond chemotherapy for this subtype of NSCLC.

The efficacy of amivantamab was confirmed for the real-world population for EGFR E20I-mutated NSCLC. PD-L1 status could be a poor predictive factor, which should be further validated.

P2, N=67, Recruiting, Janssen Research & Development, LLC | N=126 --> 67

P1/2; N=12; Recruiting; Sponsor:University of Colorado, Denver

P1/2, N=80, Recruiting, Janssen Research & Development, LLC | N=20 --> 80

P2, N=43, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

MAIC analysis showed that mobocertinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum-based chemotherapy. These findings may benefit patients by supporting future treatment options.

P2, N=180, Not yet recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2026 --> Mar 2026

No abstract available

Ami showed clinical meaningful antitumor activity in EC, especially in Met-high-expression tumors. There was minimal monotherapy activity in GC. No new safety signals were identified in pts with GC and EC, which appeared to be acceptable.

P1, N=751, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2024 --> Dec 2024

P3, N=308, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Sep 2023 --> May 2023

P3, N=1074, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2025 --> Jun 2027

P1/2, N=225, Recruiting, Janssen Research & Development, LLC | Phase classification: P1b/2 --> P1/2

P2, N=390, Recruiting, Janssen Research & Development, LLC | Trial completion date: Nov 2025 --> Jul 2026

The use of amivantamab-chemotherapy resulted in superior efficacy as compared with chemotherapy alone as first-line treatment of patients with advanced NSCLC with EGFR exon 20 insertions. (Funded by Janssen Research and Development; PAPILLON ClinicalTrials.gov number, NCT04538664.).

P2, N=18, Terminated, Janssen Research & Development, LLC | Completed --> Terminated; N~15 subjects data analysis did not meet statistical consideration of ORR and study primary/secondary objectives were not met. Enrollment was terminated for futility