FDA Approves Monthly Rybrevant Faspro in EGFR Lung Cancer

The U.S. Food and Drug Administration (FDA) has approved a new once-monthly dosing schedule for Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) in the United States, giving patients with epidermal growth factor receptor (EGFR)–mutated advanced non-small cell lung cancer (NSCLC) a simplified treatment option that may reduce clinic visits while maintaining established safety and efficacy. The therapy is used in combination with oral Lazcluze (lazertinib) for first-line treatment.

According to a news release from Johnson & Johnson, patients may transition to monthly dosing as early as week 5, after receiving weekly injections during weeks 1 through 4. The newly approved schedule delivers consistent outcomes compared with the previously approved bi-weekly subcutaneous dosing regimen.

Main data that support the findings

Data supporting the monthly dosing schedule were recently presented at the 2025 World Conference on Lung Cancer. Findings from the PALOMA-2 study showed that once-monthly Rybrevant Faspro combined with Lazcluze produced a high objective response rate in previously untreated patients with EGFR-mutated advanced NSCLC.

The study also demonstrated a significant reduction in administration-related reactions compared with historical intravenous administration. Rates of administration-related reactions were consistent with the bi-weekly subcutaneous schedule. Specifically, administration-related reactions occurred in 12% of patients receiving monthly dosing compared with 13% with bi-weekly subcutaneous dosing and 66% with historical intravenous administration.

Venous thromboembolic events were also comparable between monthly and bi-weekly subcutaneous dosing. These events occurred in 13% of patients receiving monthly dosing compared with 11% in patients who received bi-weekly subcutaneous dosing with anticoagulation and 38% in historical intravenous data without anticoagulation.

No new safety signals were identified with the monthly schedule. Only 8% of patients discontinued amivantamab due to treatment-related side effects. Mean plasma concentration levels were consistent with historical intravenous and bi-weekly subcutaneous dosing, supporting pharmacokinetic comparability.

The approval builds on the earlier FDA approval of Rybrevant Faspro, which changed administration time from hours with intravenous delivery to minutes with subcutaneous injection and demonstrated a fivefold reduction in administration-related reactions compared with intravenous delivery.

PALOMA-2 and MARIPOSA trial details

PALOMA-2 is an open-label phase 2 study evaluating the efficacy, safety and pharmacokinetics of first-line subcutaneous amivantamab administered by manual injection in combination with Lazcluze and or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. The primary end point was objective response rate.

The MARIPOSA study is a randomized phase 3 trial that enrolled 1,074 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The study compared Rybrevant plus Lazcluze versus Tagrisso (osimertinib) and versus Lazcluze alone in the first-line setting. The primary endpoint is progression-free survival as assessed by blinded independent central review. Secondary endpoints include overall survival, objective response rate, duration of response, progression-free survival after first subsequent therapy and intracranial progression-free survival.

An analysis from MARIPOSA presented at the 2025 World Congress on Lung Cancer showed that the combination significantly reduced the development of EGFR- and MET-driven resistance compared with Tagrisso in the first-line setting. MET amplifications occurred in 3% of patients receiving the combination compared with 13% of those receiving Tagrisso. Secondary EGFR mutations such as C797S were reported in 1% of patients on the combination versus 8% with Tagrisso. Acquired MET amplification led to early discontinuation in 23% of patients on Tagrisso within six months compared with 4% on the combination.

Understanding the safety of Rybrevant Faspro

Rybrevant Faspro is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. The therapy can cause hypersensitivity and administration-related reactions, including dyspnea, flushing, fever, chills, chest discomfort, hypotension and vomiting. In PALOMA-3, all grade administration-related reactions occurred in 13% of patients and 0.5% were grade 3 (severe). Most occurred with the initial dose.

Interstitial lung disease or pneumonitis has been reported with both Rybrevant Faspro and Rybrevant. In PALOMA-3, interstitial lung disease or pneumonitis occurred in 6% of patients, including grade 3 in 1%, grade 4 (life-threatening) in 1.5% and fatal cases in 1.9%. Five percent of patients permanently discontinued treatment due to interstitial lung disease or pneumonitis.

Venous thromboembolic events can occur when Rybrevant Faspro or Rybrevant is used with Lazcluze. In PALOMA-3, all grade venous thromboembolic events occurred in 11% of patients and 1.5% were grade 3. Among patients who received prophylactic anticoagulation at study entry, all grade venous thromboembolic events occurred in 7% compared with 17% in those who did not receive prophylactic anticoagulation.

Dermatologic side effects, including rash, were common. In PALOMA-3, rash occurred in 80% of patients, including grade 3 in 17% and grade 4 in 0.5%. Ocular toxicity also occurred in 13% of patients, including 0.5% grade 3 events.

Serious side effects occurred in 33% of patients treated with Rybrevant Faspro and Lazcluze in PALOMA-3. Death due to side effects occurred in 5% of patients, including interstitial lung disease or pneumonitis in 1.9% and pneumonia in 1.5%.

Patients are advised to discuss potential risks and monitoring plans with their health care team when considering treatment.

References

1. “PALOMA-2: Subcutaneous Amivantamab Administered Every 4 Weeks Plus Lazertinib in First-Line EGFR-Mutated Advanced NSCLC” by Dr. Scott S, et al., presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.

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