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

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

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

Additionally, amibantamab 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 to 19.3). . Of note, its efficacy was consistent regardless of previous therapy or response to previous platinum chemotherapy.

Forty-two percent (n = 48/114) of patients received ≥12 cycles of amibantamab and reported sustained clinical response with amibantamab. Thirteen percent of these patients had been on the drug for a median of 2.6 years and are still on it. At the time of data cutoff (September 12, 2022), 7 patients were progression-free and 8 were treated beyond disease progression.

“Sustained Clinical Benefits [amivantamab]…12 cycles [or more] associated with having good performance status, [namely an] ECOG [of 0]“…response according to RECIST criteria, with no baseline changes in the RAS/RAF/MEK pathway,” said lead study author Pilar Garrido López, M.D., Ph.D., Associate Professor of Medical Oncology at the University of Alcala, Madrid. Stated. Spain, meeting.

In May 2021, the FDA granted accelerated approval of amibantamab for use in adult NSCLC patients with latent tumors. EGFR Patients with exon 20 insertion mutations and disease progression on platinum-based chemotherapy.² This decision was based on previous CHRYSALIS data (n = 81), in which the drug induced an ORR of 40% (95% CI, 29%–51%), with a median DOR of 11.1–11.1. month (95% CI, 6.9-51%). cannot be evaluated).

This open-label phase 1 trial enrolled patients with metastatic or unresectable NSCLC who had an ECOG performance status of 0 or 1 and had progressed or failed standard therapy.³ Patients were required to have measurable disease and be eligible for the dose-expansion phase of the trial. EGFR again Met Mutation identified by next-generation sequencing. Patients with untreated or active brain metastases were excluded.

Investigators are evaluating amibantamab alone and in combination with other agents in patients with advanced NSCLC.in order to EGFR In the exon 20 insertion-positive cohort, TAGRISSO was evaluated as monotherapy and administered at the recommended phase 2 dose (RP2D) of 1050 mg in patients weighing <80 kg and 1400 mg in patients weighing ≥80 kg. I was.

The primary objective of the dose escalation phase of the study was to identify the maximum tolerated dose and RP2D of amibantamab. In the expansion phase, researchers investigated the drug’s safety, tolerability and anti-tumor activity when administered with RP2D.

In addition, Garrido López, head of the department of thoracic tumors in the Department of Medical Oncology at the Ramón y Cajal University Hospital in Madrid, reported long-term results for this patient population.

The median age of the 114 patients was 62 years (range, 36–84 years). More than half were female (61%) and Asian (52%). At baseline, 57% were never smokers, 43% were smokers, and 25% had brain metastases.

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

The researchers performed a univariate analysis to examine potential predictors of durable clinical efficacy.

“Only an ECOG performance status of 0 will have a sustained clinical effect,” Garrido López pointed out.

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 within that group [that received] Treatment cycles are less than 12 cycles,” added Garrido Lopez. “None [these alterations] occurred within the group [that received the agent for] 12 cycles or more. ”

No new safety signals were observed at long-term follow-up. The most common EGFR-related toxicities were paronychia (total, 58%, grade ≥ 3, 4%), dermatitis acneiformis (total, 47%, grade ≥ 3, 1%), rash (total, 43 %, grade ≥3, 2%), stomatitis (total 25%, grade ≥3, 1%), pruritus (total 20%, grade ≥3, 0%), diarrhea (total 18%, grade ≥3, 0%) 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 discontinuation occurred in her 29% of patients, and dose reduction occurred in 18%.

“[There were] Low treatment-related discontinuation rate [7%]. Cumulative groupings of rash and infusion-related reactions remained the most frequent toxicities,” Garrido Lopez said.

Amibantamab is currently being investigated in combination with chemotherapy for use as first-line treatment for NSCLC patients with: EGFR Exon 20 insertion mutation as part of the Phase 3 PAPILLON trial (NCT04538664).^Four

References

1. Garrido P, Girard N, Cho BC, et al. Predictors of long-term efficacy, safety, and response to amibantamab in his EGFR Ex20ins-mutated advanced NSCLC patients after platinum therapy. Presented at: European Lung Cancer Congress 2023. March 29-April 1, 2023. Copenhagen Denmark. Summary 30.

2. FDA grants early approval of amibantamab-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. Amibantamab in EGFR exon 20 insertion-mutant non-small cell lung cancer undergoing platinum chemotherapy: early results from the CHRYSALIS phase I trial. J Clin Ongol. 2021;39(30):3391-3402.doi:10.1200/JCO.21.00662

4. Brazel D, Nagasaka M. Amibantamab (JNJ61186372) for EGFR exon 20 insertion-positive non-small cell lung cancer. lung cancer (ocher). 2021; 12:133-138. Doi: 10.2147/LCTT.S33786