Rybrevant® (Amivantamab-Vmjw) Plus Lazcluze® (Lazertinib) in Non-Small Cell Lung Cancer (NSCLC) Therapy: A Chemotherapy-Free Regimen Poised to Disrupt the Oncology Market and Elevate Johnson & Johnson’s Shareholder Value

Johnson & Johnson’s (JNJ) Rybrevant (amivantamab-vmjw) and Lazcluze (lazertinib) combination therapy has emerged as a groundbreaking advancement in the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). Approved by the U.S. Food and Drug Administration (FDA) in August 2024 and the European Commission in 2025, this chemotherapy-free regimen has demonstrated statistically significant improvements in overall survival (OS) and progression-free survival (PFS) compared to AstraZeneca’s Tagrisso (osimertinib), the current standard of care [1]. With a projected market size for lung cancer therapies exceeding $60 billion by 2030, the Rybrevant/Lazcluze combination is positioned to disrupt the oncology drug landscape while delivering substantial long-term value to JNJ shareholders [2].

Clinical Efficacy: A New Standard of Care

The Phase 3 MARIPOSA trial, which underpinned the regulatory approvals, revealed compelling data. At three years of follow-up, 61% of patients receiving Rybrevant plus Lazcluze were alive compared to 53% on osimertinib. The median OS for the combination therapy was not estimable, versus 37.3 months for osimertinib [3]. Additionally, the regimen extended PFS to 23.7 months versus 16.6 months for the comparator [4]. These results, coupled with a manageable safety profile—common adverse events included paronychia, infusion-related reactions, and rash—position the therapy as a chemotherapy-free alternative with a survival advantage [5].

The regimen’s mechanism of action further strengthens its clinical appeal. Rybrevant, a bispecific antibody targeting EGFR and MET, combines with Lazcluze, a third-generation EGFR tyrosine kinase inhibitor (TKI), to address resistance mechanisms that often limit monotherapy efficacy [6]. This dual-targeting approach has been endorsed as a Category 1 recommendation in the NCCN Guidelines for first-line treatment of EGFR exon 19 deletion or L858R mutation-positive NSCLC [7].

Regulatory and Market Momentum

Regulatory approvals have accelerated the combination’s market penetration. The FDA granted accelerated approval in August 2024, while the European Commission and Health Canada followed with approvals in 2025, underscoring global recognition of its clinical benefits [8]. These milestones have enabled JNJ to secure favorable reimbursement terms and rapid adoption in key markets.

Financially, the therapy is already generating robust returns. In Q1 2025, Rybrevant/Lazcluze achieved sales of $179 million, reflecting over 100% year-over-year growth [9]. Analysts project the combination to represent a $5 billion annual sales opportunity by 2030, contributing meaningfully to JNJ’s goal of $50 billion in oncology revenue by the same year [10]. The global NSCLC market, valued at $18.56 billion in 2024, is forecasted to grow at a compound annual growth rate (CAGR) of 6.6% through 2035, with Rybrevant/Lazcluze well-positioned to capture a significant share [11].

Strategic Differentiation and Long-Term Value

The chemotherapy-free nature of Rybrevant/Lazcluze is a critical differentiator in a competitive market. Unlike traditional regimens that require cytotoxic agents, this combination reduces treatment-related toxicity while maintaining efficacy. A proactive dermatologic regimen in the Phase 2 COCOON study further mitigated side effects, reducing moderate-to-severe reactions by nearly 50% [12]. Additionally, JNJ is advancing a subcutaneous formulation of Rybrevant to reduce infusion times from five hours to five minutes, enhancing patient convenience and adherence [13].

From a shareholder value perspective, the combination therapy aligns with JNJ’s long-term strategic goals. The company’s $55 billion investment in U.S. innovation and manufacturing over the next four years reinforces its commitment to oncology leadership [14]. With Rybrevant/Lazcluze projected to drive 5–7% operational growth for JNJ’s Innovative Medicine franchise from 2025 to 2030, the therapy is a cornerstone of the company’s oncology portfolio [15].

Conclusion

Rybrevant plus Lazcluze represents a paradigm shift in EGFR-mutated NSCLC treatment, combining clinical superiority, regulatory momentum, and market differentiation. By offering a chemotherapy-free regimen with a survival advantage, JNJ has not only redefined first-line care but also secured a lucrative position in a rapidly expanding market. As the therapy scales, its impact on JNJ’s oncology revenue and shareholder value is poised to be transformative, cementing the company’s leadership in the next era of precision oncology.

Source:
[1] European Commission approves LAZCLUZE® (lazertinib) in combination with RYBREVANT® (amivantamab) for the first-line treatment of patients with EGFR-mutated non-small cell lung cancer [https://www.jnj.com/innovativemedicine/emea/newsroom/european-commission-approves-lazcluze-lazertinib-in-combination-with-rybrevant-amivantamab-for-the-first-line-treatment-of-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer]
[2] Global Non-Small Cell Lung Cancer Market Size [https://www.rootsanalysis.com/reports/squamous-non-small-cell-lung-cancer-market.html]
[3] RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) demonstrates significant overall survival benefit in patients with EGFR-mutated advanced non-small cell lung cancer versus osimertinib [https://www.biospace.com/press-releases/rybrevant-amivantamab-plus-lazcluze-lazertinib-demonstrates-significant-overall-survival-benefit-in-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer-versus-osimertinib]
[4] Amivantamab Plus Lazertinib Improves OS in EGFR-Mutant Advanced NSCLC [https://www.onclive.com/view/amivantamab-plus-lazertinib-improves-os-in-egfr-mutant-advanced-nsclc]
[5] RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) [https://www.ncbi.nlm.nih.gov/books/NBK617243/]
[6] RYBREVANT® (amivantamab-vmjw) plus LAZCLUZE™ (lazertinib) significantly outperforms standard of care in first-line EGFR-mutated lung cancer [https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-significantly-outperforms-standard-of-care-in-first-line-egfr-mutated-lung-cancer-with-compelling-new-data-at-elcc-2025-302406501.html]
[7] J&J combo survival win signals new era in EGFR lung cancer [https://www.fiercepharma.com/pharma/jj-combo-signals-new-era-egfr-lung-cancer-survival-win-against-astrazenecas-tagrisso]
[8] Health Canada authorizes LAZCLUZE (lazertinib) in combination with RYBREVANT (amivantamab) as a first-line chemotherapy-free treatment for advanced non-small cell lung cancer [https://firstwordpharma.com/story/5940989]
[9] Johnson & Johnson (JNJ) Stock Price, ... [https://www.datainsightsmarket.com/companies/JNJ]
[10] RBC maintains Outperform on Johnson & Johnson stock [https://www.investing.com/news/analyst-ratings/rbc-maintains-outperform-on-johnson--johnson-stock-181-target-93CH-3965496]
[11] Global Non-Small Cell Lung Cancer Market Size [https://www.rootsanalysis.com/reports/squamous-non-small-cell-lung-cancer-market.html]
[12] Enhanced preventive regimen demonstrates a statistically significant and clinically meaningful reduction in dermatologic reactions in patients with EGFR-mutated advanced NSCLC [https://www.jnj.com/innovativemedicine/emea/enhanced-preventive-regimen-demonstrates-a-statistically-significant-and-clinically-meaningful-reduction-in-dermatologic-reactions-in-patients-with-egfr-mutated-advanced-nsclc]
[13] J&J combo survival win signals new era in EGFR lung cancer [https://www.fiercepharma.com/pharma/jj-combo-signals-new-era-egfr-lung-cancer-survival-win-against-astrazenecas-tagrisso]
[14] Johnson & Johnson (JNJ) Stock Price, ... [https://www.datainsightsmarket.com/companies/JNJ]
[15] Johnson & Johnson (JNJ): Innovation, Market Impact, and ... [https://monexa.ai/blog/johnson-johnson-jnj-innovation-market-impact-and-f-JNJ-2025-03-28]