The FDA has approved a once-monthly subcutaneous dosing schedule for RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj), making it the first EGFR-targeted therapy that can be administered monthly. The update builds on the prior approval of subcutaneous amivantamab and is intended to simplify administration while maintaining established efficacy and safety.

“This new approval lets us treat with subcutaneous amivantamab every four weeks,” says Danny Nguyen, assistant clinical professor and general medical oncologist at City of Hope. “The first month of treatment remains weekly for four weeks, and then patients can move to once-a-month injections.”

Where This Fits in the Treatment Landscape

Amivantamab plus lazertinib is a first-line option for patients with EGFR exon 19 deletion or L858R–mutated advanced non–small cell lung cancer (NSCLC). In the MARIPOSA trial, the combination demonstrated superior progression-free survival and an emerging overall survival advantage compared with Tagrisso (osimertinib), the long-standing standard of care.

The monthly subcutaneous schedule does not change who is eligible for treatment or expectations around efficacy. Instead, it changes how the therapy is delivered.

“It’s not that the drug is more effective,” Dr. Nguyen notes. “It appears to have fewer administration-related reactions, is more convenient for patients, and frees up capacity in infusion centers.”

Administration and Dosing

The updated schedule is straightforward:

• Induction: Weekly subcutaneous dosing for the first 4 weeks

• Maintenance: Once every 4 weeks thereafter

• Premedication: Typically unchanged (acetaminophen, antihistamine, steroid on treatment day; optional steroid lead-in per institutional practice)

• Administration time: Injection over approximately 4–5 minutes, followed by observation

For clinics accustomed to IV amivantamab, this represents a shift from multi-hour infusions—particularly during early dosing—to brief injection visits.

“Practically and logistically, patients who travel long distances or have work and family obligations don’t have to spend nearly as much time in clinic,” Dr. Nguyen says.

Operational Impact

Beyond convenience for patients, the shift to monthly subcutaneous administration may have meaningful operational benefits:

• Reduced chair time and scheduling complexity

• Decreased nursing workload associated with infusion setup and monitoring

• Greater flexibility to accommodate additional patients

• Potential improvement in adherence due to fewer visits

Together, these factors may ease pressure on infusion centers without compromising outcomes.

Safety Profile and Monitoring

Experience with subcutaneous amivantamab suggests lower rates of administration-related reactions compared with historical IV data, as well as a potentially lower risk of thromboembolic events. However, EGFR-related dermatologic toxicities remain common and require proactive management.

“I think follow-up stays about the same,” Dr. Nguyen says. “We still advise patients closely about skin toxicities and other side effects. The monitoring doesn’t change — but the delivery does.”

Most adverse events occur within the first four months of treatment. Importantly, temporary dose holds during this period have not been shown to compromise progression-free survival, supporting flexibility in toxicity management.

Why This Matters

The approval does not redefine the standard of care — it refines how that standard is delivered.

It preserves the efficacy of a highly active targeted regimen while:

• Improving tolerability

• Reducing time in clinic

• Lessening system burden

• Enhancing patient experience

“The subcutaneous formulation is one of those incremental advances that keeps adding on,” Dr. Nguyen says. “It helps patients live longer and hopefully with improved quality of life.”