Subcutaneous Amivantamab Is Associated With Increased Tolerability in Solid Tumors

The subcutaneous administration of amivantamab-vmjw (Rybrevant) led to low rates of infusion-related reactions and an overall safety profile consistent with that historically associated with the intravenous (IV) administration of the drug in patients with advanced solid tumors, according to Anna Minchom, MB BCh, MRCP, MD.

The phase 1 PALOMA trial (NCT04606381) investigated the feasibility, safety, and pharmacokinetics of various formulations of subcutaneous amivantamab in patients with advanced solid tumors who were predicted to benefit from EGFR- or MET-targeted therapy to determine the recommended phase 2 dose (RP2D) of this agent. In this trial, the rate of infusion-related reactions or symptoms associated with infusion-related reactions with subcutaneous administration of the agent was 16%.¹ In contrast, in the initial readout of the phase 1 CHRYSALIS trial (NCT02609776), which investigated amivantamab in patients with EGFR exon 20 insertion–mutated non–small cell lung cancer (NSCLC), the rate of infusion-related reactions or symptoms associated with infusion-related reactions with IV administration of amivantamab was 66%.²

“Subcutaneous administration of amivantamab negates the need for split dosing, prolonged observation periods, and prolonged infusion times, with low rates of infusion-related reactions,” Minchom said in an interview with OncLive® during the 2023 ASCO Annual Meeting. “[Thus, subcutaneous] administration [of this agent is] much more feasible [than IV administration].”

In the interview, Minchom discussed the need to develop an amivantamab administration method that decreases the likelihood of infusion-related reactions in patients with solid tumors, revealed the RP2D of subcutaneous amivantamab that was determined in the PALOMA trial, and emphasized potential future directions with this agent.

Minchom is a consultant medical oncologist and BRC clinical scientist in the Drug Development and Lung Units at the Royal Marsden Hospital and the Institute of Cancer Research in London, United Kingdom.

OncLive: What was the rationale for the PALOMA trial?

Minchom: Amivantamab is a MET-/EGFR-targeted bispecific antibody that is licensed for use in [patients with] NSCLC with EGFR exon 20 insertion mutations and is being investigated in other subtypes of EGFR-mutated lung cancer. This drug is given intravenously, but it carries the problem of infusion-related reactions, [which are] reactions [that occur] after the drug is given, and which necessitate long infusion times and observation periods. This study is investigating a subcutaneous preparation of amivantamab to overcome those infusion-related reactions.

What patient populations were observed in PALOMA?

This trial recruited patients with all cancer types. The main end points of the trial were to evaluate the pharmacokinetics of the subcutaneous preparation [of amivantamab] and compare this with the IV preparation to determine the RP2D of that subcutaneous preparation.

What was the frequency of infusion-related reactions in this study?

[With] the IV preparation, there were high infusion-related reaction rates. With the subcutaneous preparation, the rate was 16%. Importantly, they were all grade 1 and 2 reactions; there were no grade 3 or 4 reactions. [In addition], the subcutaneous preparation was feasible to administer. It was given around the umbilicus, the abdominal subcutaneous tissue, and there was little irritation around the injection site.

What other safety findings from PALOMA are important to mention?

The other adverse effects associated with amivantamab have already been well documented in [studies investigating the] IV preparation. They seem similar with the subcutaneous preparation. For example, rash was reasonably common, [although it was observed in] reasonably low numbers in this subcutaneous trial. However, broadly speaking, [the safety profile of subcutaneous amivantamab] seems similar to [that of] IV amivantamab.

Based on these findings, what was determined to be the RP2D of subcutaneous amivantamab?

Several dose schedules were explored. For the once every 2 weeks regimen, the RP2D was dose banded. For patients [who weigh less than] 80 kg, it’s 1600 mg. For those [who weigh at least] 80 kg, it’s 2240 mg. The once every 3 weeks preparation is slightly different. That’s 2560 mg for those [who weigh less than] 80 kg, and 3360 mg for those [who weigh at least] 80 kg.

What are the next steps for this research?

It’s hoped that this subcutaneous preparation can be substituted for the IV preparation in ongoing trials. Several trials of interest are ongoing, for example, the phase 2] PALOMA-2 trial [NCT05498428] and the [phase 3] PALOMA-3 trial [NCT05388669].

What else were you excited to see come out of the 2023 ASCO Annual Meeting?

[I enjoyed] all the EGFR data and the new drugs that are coming out and being explored. Lung cancer with EGFR exon 20 insertion mutations [is an] interest of mine. [I was also] interested in the neoadjuvant data for NSCLC management. 

References

1. Minchom AR, Krebs MG, Cho BC, et al. Subcutaneous amivantamab (ami) in patients (pts) with advanced solid malignancies: the PALOMA study—updated safety and identification of the recommended phase 2 dose. J Clin Oncol. 2023;41(suppl 16):9126. doi:10.1200/JCO.2023.41.16_suppl.9126
2. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: initial results from the CHRYSALIS phase I study. J Clin Oncol. 2021;39(30):3391-3402. doi:10.1200/JCO.21.00662