[MP Test] Once-monthly subcutaneous amivantamab fares well in advanced solid tumours

In individuals with advanced solid malignancies, subcutaneous (SC) amivantamab administered once a month is associated with fewer infusion-related reactions (IRRs) and offers more convenience than the IV formulation, the phase Ib PALOMA study suggest.

“The incidence of IRRs and their severity are markedly reduced with SC administration Q4W compared to the historic experience of IV amivantamab Q2W (16 percent vs 67 percent),” said Dr Natasha Leighl from The Princess Margaret Cancer Centre, Toronto, Ontario, Canada, at ELCC 2024. To further put it into context, the 16 percent represents only three of the 19 patients in the SC arm, and all IRRs were grade 1/2.

Moreover, apart from one patient who received treatment for pruritus, none required additional supportive care. “With resumption of dosing, no recurrent IRRs were seen,” added Leighl.

The most common treatment-emergent adverse events (TEAEs) were mediated through EGFR and MET inhibition and were mostly grade 1/2. Of the nine patients who had grade 3 toxicities, only three were deemed treatment-related. [ELCC 2024, abstract 6MO]

Of note, 15 patients reported rash, but only two of the cases were grade 3. The rash resolved with dose management.

Why switch from IV to SC?

IV amivantamab is associated with a high rate of low-grade reactions, noted Leighl. “To manage this, the first dose is usually split over 2 days at a lower infusion rate for an approximate infusion time of 4 hours.”

Switching to the SC route would offer benefits for both patients and providers, noted discussant Dr Hazel O’Sullivan from Cork University Hospital, Cork, Ireland, at ELCC 2024. “For patients, it is more comfortable, has a shorter infusion time, and has less risks of AEs … For [providers], it has been shown to reduce resource strain. In fact, switching to the SC route has been shown to reduce [provider] active time by >50 percent.”

However, O’Sullivan was quick to point out that the SC route is not without challenges. “It can have variable absorption, delayed bioavailability, and requires a higher drug dose delivery.”

In PALOMA, Leighl and team initially evaluated the Q2W and Q3W dosing of SC amivantamab. [J Clin Oncol 2023;41;9126] In the current analysis, they investigated the Q4W dosing of SC amivantamab in 19 heavily pre-treated patients (median age 62 years, 53 percent women, 68 percent Asian). Seventeen patients had lung adenocarcinoma.

To better match the steady-state C_trough levels of the reference IV Q2W dose, the Q4W dosing has been refined to 3,520 mg (4,640 mg for those ≥80 kg). “With [these doses], we achieved comparable exposure to the approved IV Q2 weekly dose. Administration time was 7–10 minutes, with less severe and a markedly lower rate of IRRs,” Leighl said.

Takeaways

“The main take-home message is that the IRR risk is just a quarter – with 16 percent having IRRs with SC amivantamab vs 67 percent with IV amivantamab – and there were no grade 3 IRRs,” said O’Sullivan.

Therefore, looking at the assessment criteria for SC vs IV formulations, is SC amivantamab safe and tolerable compared with the IV formulation?, O’Sullivan continued. “Certainly. There may be more rash, but there are [fewer] IRRs … and the administration time has been brought down from hours to mere minutes.”

“The fact that treatment can be given successfully for 7 minutes Q4W instead of 2–4 hours every 2 or 3 weeks – with similar exposure to avoid compromising efficacy – is a major benefit,” commented Professor Benjamin Besse from Institut Gustave Roussy, Villejuif, France, in another report.

The PALOMA 2 and 3 trials are underway to ascertain the potential of SC amivantamab in combination with lazertinib in lung cancer cohorts.