Long-term Benefit of Amivantamab Continues in Postplatinum NSCLC

Publication
Article
Targeted Therapies in OncologyMay 2023
Volume 12
Issue 7
Pages: 27

Amivantamab elicited an objective response rate of 37% per investigator assessment, with a median duration of response of 12.5 months, according to long-term data from the CHRYSALIS trial.

Long-term data from the CHRYSALIS trial (NCT02609776) continued to demonstrate clinical benefit for amivantamabvmjw (Rybrevant), according to findings presented at the European Lung Cancer Congress 2023 in Copenhagen, Denmark.1

At a median follow-up of 19.2 months, median progression-free survival (PFS) with the agent was 6.9 months (95% CI, 5.6-8.8), and the 2-year PFS rate was 13.7%. Median overall survival (OS) was 23 months (95% CI, 18.5-29.5), and the 2-year landmark OS rate was 47.2%.

Moreover, amivantamab elicited an objective response rate (ORR) of 37% (95% CI, 28%-46%) per investigator assessment, with a median duration of response (DOR) of 12.5 months (95% CI, 6.9-19.3). Notably, its efficacy was consistent irrespective of previous therapies or response to prior platinum chemotherapy.

Forty-two percent of patients (n = 48/114) were reported to have sustained clinical benefit with amivantamab, having received it for 12 or more cycles. Thirteen percent of these patients had been receiving the agent for a median of 2.6 years and were still receiving it. At the time of data cutoff (September 12, 2022), 7 patients were progression free and 8 were receiving treatment beyond disease progression.

“Sustained clinical benefit with [amivantamab]…for 12 cycles [or more] was associated with having a good performance status, [namely an] ECOG [of 0]…a response according to RECIST criteria, and not having a baseline alteration in the RAS/RAF/MEK pathway,” said Pilar Garrido López, MD, PhD, lead study author and associate professor of medical oncology at Universidad de Alcalá, in Madrid, Spain, at the meeting.

In May 2021, the FDA granted accelerated approval to amivantamab for use in adults with NSCLC whose tumor harbors EGFR exon 20 insertion mutations and whose disease had progressed on platinum-based chemotherapy.2 The decision was based on earlier data from CHRYSALIS (n = 81), in which the agent induced an ORR of 40% (95% CI, 29%-51%) with a median DOR of 11.1 months (95% CI, 6.9-not evaluable).

The open-label, phase 1 study enrolled patients with metastatic or unresectable NSCLC who had an ECOG performance status of 0 or 1 and had progressed on or were not able to receive standard treatment.3 For the dose-expansion phase of the trial, patients were required to have measurable disease and qualifying EGFR or MET mutations identified via next-generation sequencing. Those with untreated or active brain metastases were excluded.

Investigators are evaluating the use of amivantamab alone and in combination with other agents in patients with advanced NSCLC. For the EGFR exon 20 insertion– positive cohort, the agent was evaluated as a monotherapy and administered at the recommended phase 2 dose (RP2D) of 1050 mg in patients weighing less than 80 kg and of 1400 mg in those weighing at least 80 kg.

The primary objective of the doseescalation phase of the study was to identify the maximum tolerated dose and RP2D of amivantamab. In the expansion phase, investigators examined the safety, tolerability, and antitumor activity of the agent when administered at the RP2D.

In addition, Garrido López, who is also head of the Thoracic Tumors Section in the Medical Oncology Department of University Hospital Ramón y Cajal, in Madrid, reported long-term results for this patient population.

Median age among the 114 patients was 62 years (range, 36-84). More than half were female (61%) and Asian (52%). Fifty-seven percent were nonsmokers, 43% smokers, and 25% had brain metastases at baseline.

This was a heavily pretreated population with a median of 2 prior lines of therapy (range, 1-7). All patients had previously received platinum-based chemotherapy, 44% had prior immunotherapy, and 20% a prior EGFR tyrosine kinase inhibitor.

Investigators conducted a univariate analysis to examine potential predictors of sustained clinical benefit.

“Only an ECOG performance status of 0 was associated with sustained clinical benefit,” Garrido López noted.

All patients were required to submit a plasma sample at baseline for circulating tumor DNA analysis. “Patients with baseline alterations in the RAS/RAF/MEK pathway were only seen in the group [that received] less than 12 treatment cycles,” Garrido López added. “None of [these alterations] occurred in the group [that received the agent for] 12 cycles or more.”

No new safety signals were observed with longer follow-up. The most common EGFR-related toxicities were paronychia (total, 58%; grade ≥ 3, 4%), dermatitis acneiform (total, 47%; grade ≥ 3, 1%), rash (total, 43%; grade ≥ 3, 2%), stomatitis (total, 25%; grade ≥ 3, 1%), pruritus (total, 20%; grade ≥ 3, 0%), and diarrhea (total, 18%; grade ≥ 3, 4%). The most common MET-related adverse effects (AEs) were hypoalbuminemia (total, 39%; grade ≥ 3, 4% ) and peripheral edema (total, 27%; grade ≥ 3, 1%).

Other toxicities included infusion-related reactions (67%), nausea (28%), constipation (26%), and fatigue (26%). Treatment-related dose interruptions occurred in 29% of patients and dose reductions in 18%.

“[There were] low rates of treatmentrelated discontinuations [7%]. Cumulative grouped rash and infusion-related reactions remained the most frequent toxicities,” Garrido López said.

Amivantamab is now being explored in combination with chemotherapy for use as a first-line treatment in patients with NSCLC harboring EGFR exon 20 insertion mutations as part of the phase 3 PAPILLON trial (NCT04538664).4

REFERENCES
1. Garrido P, Girard N, Cho BC, et al. Long-term efficacy, safety and predictors of response to amivantamab among patients with post-platinum EGFR Ex20ins-mutated advanced NSCLC. Presented at: 2023 European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Abstract 30.
2. FDA grants accelerated approval to amivantamab-vmjw for metastatic non-small cell lung cancer. FDA. May 21, 2021. Accessed March 29, 2023. http://bit.ly/3Ks1jW2
3. 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
4. Brazel D, Nagasaka M. Spotlight on amivantamab (JNJ61186372) for EGFR exon 20 insertions positive non-small cell lung cancer. Lung Cancer (Auckl). 2021;12:133-138. doi:10.2147/LCTT.S33786
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