Rybrevant (amivantamab-vmjw)

Our study concluded that combination regimens based on third-generation TKIs (osimertinib plus ramucirumab, osimertinib plus chemotherapy, osimertinib plus bevacizumab, amivantamab plus lazertinib and aumolertinib plus apatinib) could be the new and clinically preferable first-line, standard of care for EGFR-mutated advanced non-small cell lung cancer.

P1/2 | "Clinical Trial Registration Number: NCT05379595. The abstract will be released to the public on January 21, 2025 at 10:00 PM UTC"

P3, N=1000, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting | Trial completion date: Jan 2032 --> Dec 2032

In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases...Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

Rational combinations of third-generation EGFR TKIs with anti-angiogenic drugs, chemotherapy, the EGFR-MET bispecific antibody amivantamab or local tumour ablation are being investigated as strategies to delay drug resistance and increase clinical benefit...In this Review, we describe the current first-line treatment options for EGFR-mutant NSCLC, provide an overview of the mechanisms of acquired resistance to third-generation EGFR TKIs and explore novel promising treatment strategies. We also highlight potential avenues for future research that are aimed at improving the survival outcomes of patients with this disease.

P2, N=365, Recruiting, Janssen Research & Development, LLC | Not yet recruiting --> Recruiting

P1/2, N=217, Recruiting, Janssen Research & Development, LLC | N=117 --> 217

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