Long-term benefits of amivantamab continue in post-platinum NSCLC

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

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

In addition, amivantamab elicited an objective response rate (ORR) of 37% (95% CI, 28% to 46%) by investigator assessment, with a median duration of response (DOR) of 12.5 months (95% CI, 6.9 to 19.3) . Notably, its effectiveness was consistent regardless of prior treatments or response to prior platinum-based chemotherapy.

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

“Sustainable clinical benefit with [amivantamab]…for 12 cycles [or more] was associated with a good performance index, [namely an] ECOG [of 0]…a response according to RECIST criteria, and showing no baseline alteration in the RAS/RAF/MEK pathway,” said Pilar Garrido López, MD, PhD, lead study author and associate professor of medical oncology. at the University of Alcalá, in Madrid, Spain, in Reunion.

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 previous CHRYSALIS data (n=81), in which the agent induced an ORR of 40% (95% CI, 29%-51%) with a median ORR 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 or were unable to receive standard therapy.³ For the dose expansion phase of the trial, patients had to have measurable disease and qualify EGFR Or ENCOUNTER mutations identified by next-generation sequencing. Those with untreated or active brain metastases were excluded.

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

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

Additionally, Garrido López, who is also head of the thoracic tumors section of the medical oncology department at Ramón y Cajal University Hospital, Madrid, reported long-term results for this patient population.

The median age among the 114 patients was 62 years (range, 36-84). More than half were women (61%) and Asians (52%). Fifty-seven percent were non-smokers, 43% smokers, and 25% had brain metastases at baseline.

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

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

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

All patients were required to submit a plasma sample at baseline for analysis of circulating tumor DNA. “Patients with baseline RAS/RAF/MEK pathway alterations were observed only in the group [that received] less than 12 treatment cycles,” added Garrido López. “None of [these alterations] happened 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 reactions (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 treatment-related dropouts [7%]. Cumulative cluster rashes and infusion-related reactions remained the most common toxicities,” said Garrido López.

Amivantamab is currently being studied in combination with chemotherapy for use as a first-line treatment in patients with NSCLC EGFR exon 20 insertion mutations in the Phase 3 PAPILLON trial (NCT04538664).⁴

THE REFERENCES

1. Garrido P, Girard N, Cho BC, et al. Long-term efficacy, safety, and predictors of response to amivantamab in patients with advanced NSCLC with post-platinum EGFR Ex20ins mutation. Presented at: European Lung Cancer Congress 2023; March 29-April 1, 2023; Copenhagen, Denmark. Summary 30.

2. FDA grants expedited approval for 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 non-small cell lung cancer mutated by EGFR exon 20 insertion evolving under platinum-based chemotherapy: first results from the phase I CHRYSALIS 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 positive insertions in non-small cell lung cancer. Lung cancer (Auckl). 2021;12:133-138. doi:10.2147/LCTT.S33786