Rybrevant (amivantamab-vmjw)

Our findings contribute to the evolving standard of care for this specific population and highlight the clinical benefits of targeted cancer therapies.

P2, N=365, Not yet recruiting, Janssen Research & Development, LLC

P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

P1, N=12, Recruiting, Institute of Cancer Research, United Kingdom | Not yet recruiting --> Recruiting

P3, N=1000, Not yet recruiting, Janssen Research & Development, LLC

P2, N=200, Recruiting, Janssen Research & Development, LLC | N=300 --> 200

P1, N=701, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=460 --> 701

Recently, amivantamab and sunvozertinib have demonstrated notable efficacy as first-line treatments, and several other promising novel targeted drugs are also challenging the status quo of traditional first-line platinum-based chemotherapy regimens. These developments are anticipated to further improve survival outcomes for NSCLC patients with EGFR ex20ins mutations. Hence, this review summarizes the epidemiology, molecular attributes, detection methodologies, and therapeutic advancements for EGFR ex20ins mutations in NSCLC, and briefly discusses the mechanisms of drug resistance.

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. S1900J (MET amplification) is opening fall 2024 and is studying amivantamab in NSCLC...One hundred seventy-four (5%) 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.

P1, N=12, Not yet recruiting, Institute of Cancer Research, United Kingdom

No abstract available

Infusion-related reactions (IRRs) ranged from 42% to 78% among patients that received amivantamab intravenously, while a 13% IRR rate was found in a group of patients that received amivantamab subcutaneously. Current evidence suggests that amivantamab is an effective treatment option for patients with advanced or metastatic NSCLC with EGFR mutations. Amivantamab-based combinations may prolong survival both in the treatment of naïve patients and those who have progressed on chemotherapy or tyrosine kinase inhibitors.

Firstly Mobocertinib and Amivantamab obtained approval from U.S. Food and Drug Administration (FDA) for EGFR ex20ins mutant NSCLC patients, then other drugs, such as Sunvozertinib, made breakthroughs and combination therapies also obtained gains. As mentioned above, it's definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs. This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins..

Most IRRs occurred during the infusion, were low grade, and were manageable with intervention strategies or treatment modifications. Advanced practitioners are critical in preventing, diagnosing, and managing IRRs, including educating patients and families, accurately administering infusions, prescribing premedications, and closely monitoring for IRRs.

Finally, we demonstrated that in lung adenocarcinoma patients, high expression of AREG and EGFR mutations were mutually exclusive. In conclusion, these data 1) highlight EGFR ligand AREG as a driver of tumor growth in some EGFRWT NSCLC models, 2) illustrate the preclinical efficacy of amivantamab in ligand-driven EGFRWT NSCLC, and 3) identify AREG as a potential predictive biomarker for amivantamab activity in EGFRWT NSCLC.

No abstract available

P1/2, N=57, Active, not recruiting, Janssen Research & Development, LLC | Recruiting --> Active, not recruiting | N=161 --> 57

P1, N=460, Recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Jun 2026

P3, N=776, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2025 --> Jun 2026

P2, N=74, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2026 --> Oct 2025

We report the first two cases of EGFR exon20ins SCLC, treated with amivantamab and TKIs.

P1/2, N=100, Recruiting, Janssen Research & Development, LLC

In PAPILLON (NCT04538664), amivantamab plus carboplatin-pemetrexed (amivantamab-chemotherapy) demonstrated significantly longer progression-free survival (PFS) versus chemotherapy (hazard ratio [HR], 0.395 [95% confidence interval [CI], 0.30-0.53]; P <0.0001). Consistent benefit favoring amivantamab-chemotherapy was seen across all Ex20ins sites. Amivantamab-chemotherapy is the first-line, standard of care for Ex20ins advanced NSCLC.

SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.

P3, N=1074, Active, not recruiting, Janssen Research & Development, LLC | Trial primary completion date: Apr 2024 --> Aug 2023

No abstract available

Ami+laz had significantly lower rates of EGFR and MET resistance alterations with trends for lower rates of TP53 resistance mutations and RB1 loss compared with osi. These initial findings suggest that first-line ami+laz is changing the biology of acquired resistance and demonstrate clear proof of mechanism with potent inhibition of resistance via the EGFR and MET pathways.

Amivantamab plus chemotherapy is unlikely to be a cost-effective option for NSCLC patients with EGFR exon 20 insertions. Reducing the cost of amivantamab may produce favorable economic outcomes.

Our study revealed EGFR-dependent and -independent mechanisms of mobocertinib resistance in patients with advanced EGFR Ex20ins-mutant NSCLC.

Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

Amivantamab-lazertinib showed superior efficacy to osimertinib as first-line treatment in EGFR-mutated advanced NSCLC. (Funded by Janssen Research and Development; MARIPOSA ClinicalTrials.gov number, NCT04487080.).

Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy.

This article encompasses a review of the benefits of amivantamab for patients with non-small cell lung cancer (NSCLC). This drug is the first therapy directed against this specific mutation, and unlike others, it could bind to two genetic receptors, whereas antibodies, in general, are directed toward a single receptor.

After left lower lobectomy, she subsequently developed bilateral pulmonary metastases and began treatment with her first EGFR tyrosine kinase inhibitor in 2003 with gefitinib...In the interim, she was treated with osimertinib from 2016 to 2021 until she developed progression in bilateral lung nodules...Recently her treatment was switched to afatinib, and she quickly obtained clinical improvement...Second, amivantamab is a reasonable treatment option for patients with an EGFR-KDD. Lastly, EGFR-targeted resistance mechanisms can evolve over time and space, and biopsies at the time of resistance can help inform treatment recommendations.

P1/2, N=60, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P1/2, N=117, Recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2026 --> Mar 2027

This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling.

Nivolumab and pembrolizumab are anti-PD-1 antibodies that improve immunosuppression by binding to programmed death-1 (PD-1), leading to an antitumor effect...Sym004 and amivantamab are antibodies that target the epidermal growth factor receptor and have demonstrated efficacy in the treatment of other tumors in recent phase I studies. Furthermore, clinical trials on antibody-drug conjugates such as enfortumab vedotin and DS-7300 for solid tumors are currently ongoing. The standard first-line treatments for patients with advanced ESCC contain ICIs. Therefore, drugs with different mechanisms of action that can overcome resistance to ICIs are needed as second-line or later-line treatments to improve clinical outcomes in these patients.

Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival.

Amivantamab (JNJ-372) and mobocertinib (TAK-788) have been reported to have favorable therapeutic effect for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations. NGS is more advantageous and strongly recommended for the detection of EGFR ex20ins mutations. Considering the fast and cost-effective ARMS detection method, it is suggested that the primers design should be updated according to the characteristics of EGFR ex20ins mutations in Chinese NSCLC patients.

As patients carrying EGFR exon20ins may be eligible for treatment with novel therapeutics-the bispecific antibody amivantamab, the TKI mobocertinib, or potential future innovations-they need to be identified reliably in clinical practice for which quality-based routine genetic testing is crucial. Most of these mutation-/allele-specific (q)PCR assays are not designed to detect the whole spectrum of EGFR exon20ins mutations leading to false negative results. These data suggest that NGS is a suitable method to detect EGFR exon20ins in various types of patient samples and is superior to the detection spectrum of commercially available assays.

The retrospective subgroup analysis of IMpower150 indicated that the quad regimen (carboplatin, paclitaxel, bevacizumab, atezolizumab) improved PFS and overall survival (OS) in patients with EGFR-mutant NSCLC who progressed on first-generation EGFR-TKIs...MARIPOSA-2 provided the first randomized trial post-osimertinib in EGFR-mutant NSCLC patients with another quad regimen (platinum, pemetrexed, lazertinib, amivantamab)...Here, we discuss how the results of IMpower151 and ATTLAS may rejuvenate interest in a non-EGFR containing quad regimen as a potential post-osimertinib monotherapy treatment. Randomized trials comparing the results of these studies, including the quad regimen of MARIPOSA-2 versus the quad regimen of IMpower151/Impower150/ATTLAS in post-osimertinib (or other 3G EGFR-TKI) progression, are urgently needed.