RYBREVANT®Johnson’s with chemotherapy shows improved survival outcomes for EGFR-mutated NSCLC patients in Johnson & Johnson’s Phase 3 MARIPOSA-2 study.

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Johnson & Johnson

Johnson & Johnson (NYSE: JNJ) announced significant findings from the Phase 3 MARIPOSA-2 clinical trial, demonstrating that RYBREVANT® (amivantamab-vmjw) combined with chemotherapy offers substantial benefits for patients with previously treated non-small cell lung cancer (NSCLC).

The study focused on individuals with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations, both common in this type of lung cancer.

The results, presented at the 2024 European Society of Medical Oncology (ESMO) Congress, highlight a potential breakthrough in treatment, showing improved overall survival (OS) and better patient outcomes than chemotherapy alone.

Promising Results from MARIPOSA-2: A New Hope for Lung Cancer Patients

In the second interim analysis of the MARIPOSA-2 trial, the combination of RYBREVANT® and chemotherapy demonstrated a strong trend toward improved overall survival compared to chemotherapy alone.

With a median follow-up of 18.1 months, 50% of patients receiving the combination therapy were still alive at the 18-month landmark, compared to 40% of those treated with chemotherapy alone.

The median overall survival for the RYBREVANT® group was 17.7 months, compared to 15.3 months for the chemotherapy-only group.

This represents a significant improvement, with a hazard ratio (HR) of 0.73 (95% confidence interval [CI], 0.54–0.99; nominal P=0.039), indicating a reduction in the risk of death.

The data also revealed a marked improvement in treatment adherence, with nearly five times as many patients remaining on RYBREVANT® therapy at the 18-month mark (22%) compared to chemotherapy alone (4%).

The median time to treatment discontinuation (TTD) was 10.4 months for the RYBREVANT® group versus 4.5 months for chemotherapy (HR, 0.42; 95% CI, 0.33–0.53; nominal P<0.0001).

Treatment Impact: Reducing Symptomatic Progression and Prolonging Therapy

In addition to prolonging survival, the combination of RYBREVANT® plus chemotherapy reduced the risk of symptomatic progression by 27%.

The median time to symptomatic progression (TTSP) was 16.0 months for the combination therapy group, compared to 11.8 months for those receiving chemotherapy alone (HR, 0.73; 95% CI, 0.55–0.96; nominal P=0.026).

Furthermore, the time to subsequent therapy was significantly prolonged with the combination treatment, offering a median time to subsequent therapy (TTST) of 12.2 months, compared to 6.6 months for chemotherapy (HR, 0.51; 95% CI, 0.39–0.65; nominal P<0.0001).

Patients also experienced a 36% reduction in the risk of second disease progression or death, with the median progression-free survival (PFS2) reaching 16.0 months for the RYBREVANT® group versus 11.6 months for chemotherapy alone (HR, 0.64; 95% CI, 0.48–0.85; nominal P=0.002).

Outcome	RYBREVANT® + Chemotherapy	Chemotherapy Alone	Hazard Ratio (HR)
Median Overall Survival (OS)	17.7 months	15.3 months	0.73
Patients Alive at 18 Months	50%	40%	N/A
Median Time to Treatment Discontinuation (TTD)	10.4 months	4.5 months	0.42
Median Time to Symptomatic Progression (TTSP)	16.0 months	11.8 months	0.73
Median Time to Subsequent Therapy (TTST)	12.2 months	6.6 months	0.51
Median Progression-Free Survival (PFS2)	16.0 months	11.6 months	0.64

Expert Reactions: A Step Forward in Lung Cancer Treatment

Renowned oncologists and researchers are enthusiastic about the study’s results, emphasizing the potential of RYBREVANT® to alter the treatment landscape for EGFR-mutated NSCLC.

Professor Sanjay Popat, FRCP, Ph.D., a medical oncologist at the Royal Marsden Hospital and the Institute of Cancer Research in the United Kingdom, remarked on the significance of the findings:

“The positive overall survival trend seen in MARIPOSA-2 is up-and-coming, suggesting that amivantamab combined with chemotherapy could change the treatment landscape for a population that has historically faced limited options. By helping more patients stay on treatment for longer, we improve their chances for better outcomes.”

Dr. Joshua Bauml, Vice President of Lung Cancer Disease Area Stronghold Leader at Johnson & Johnson Innovative Medicine, echoed these sentiments.

“We are pleased to see that RYBREVANT® plus chemotherapy continues to show improved survival outcomes after a year and a half of follow-up, providing real benefits to patients with few other options. These results underscore the potential of this combination regimen to make a meaningful difference for patients, and we anticipate continued improvement as we move toward the final analysis.”

Safety Profile: Consistent with Previous Findings

The safety profile of RYBREVANT® in combination with chemotherapy was consistent with the known profiles of both treatments. Permanent discontinuation of RYBREVANT® due to adverse reactions occurred in 11% of patients, with side effects generally manageable. These results reassure us that the combination treatment is safe and well-tolerated, especially considering its survival benefits.

European Commission Approval: A New Treatment Option for NSCLC

In August 2024, the European Commission approved the use of RYBREVANT® plus chemotherapy as a treatment for patients with previously treated NSCLC harboring common EGFR mutations. This approval was based on the superior efficacy and safety profile demonstrated in the MARIPOSA-2 study.

The approval marks a significant advancement in the treatment of non-small cell lung cancer, giving patients with limited options a new, more effective therapy.

Conclusion: A Groundbreaking Therapy for Lung Cancer

The results of the Phase 3 MARIPOSA-2 study offer hope for the future of lung cancer treatment, particularly for patients with EGFR-mutated NSCLC. With improved survival outcomes, reduced symptomatic progression, and better treatment adherence, RYBREVANT® combined with chemotherapy can potentially change the standard of care for these patients.

As the world continues to battle the burden of non-small cell lung cancer, the approval of RYBREVANT® in combination with chemotherapy signals a new era of personalized treatments aimed at providing better outcomes for patients who need them most.

Trivia

Did you know? Lung cancer remains the leading cause of cancer deaths worldwide, accounting for approximately 25% of all cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common form, making up about 85% of all lung cancer cases. Treatments like RYBREVANT® off