ASCO Denver 2024: Dr Salgia Discusses the MARIPOSA and PALOMA-3 Trials in NSCLC with EGFR Mutations

Presented by:

Ravi Salgia, MD, PhD, City of Hope

 Meeting:

2024 ASCO Direct ™ Denver

The Bottom Line

Results from a recently reported clinical trial suggest that the combination of amivantamab (AMI) and lazertinib (LAZ), two different types of targeted treatment, is an effective treatment option for some patients with advanced non-small cell lung cancer (NSCLC) who have specific mutations in the epidermal growth factor receptor (EGFRm) and/or other high risk features.  Results from a separate study further suggest that a subcutaneous form of AMI was at least as effective, but better tolerated than an intravenous formulation of AMI, when used as a component of the AMI-LAZ combination inEGFRm NSCLC patients.

Background

 Results from the previously reported LAURA Trial and others have established osimertinib, an orally administered tyrosine kinase inhibitor (TKI) type drug as the new standard of care for patients with stage III epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC) that is not amenable to curative intent surgery (unresectable).  Certain individuals, however, such as those with specific mutations like Ex19Del or L858R EGFRm NSCLC may represent a more resistant and challenging to treat population.  In addition, many of these NSCLC patients may present with additional high-risk features, such as spread of their disease (metastases) to the brain or liver, an accompanying mutation in the TP53 gene (TP53m) and detectable residual disease at the start of treatment (EGFRm circulating tumor DNA positive).  Two trials presented at this year’s annual meeting of the American Society for Clinical Oncology (ASCO) examined the use of a two drug combination in EGFRm NSCLC, amivantamab (AMI), a bispecific antibody type therapy, and lazertinib (LAZ), a 3rd generation EGFR TKI type therapy that is central nervous system penetrant, meaning it is able to penetrate into areas like the brain with its anticancer activity. The MARIPOSA trial examined the activity of the AMI-LAZ combination as compared to osimertinib in patients with EGFRm NSCLC and high risk features.  The PALOMA-3 trial examined the use of a subcutaneous (SC) versus intravenously (IV) administered formulation of AMI with the combination therapy.

MARIPOSA

In MARIPOSA, a phase III study, the primary endpoint of progression-free survival (PFS) was significantly improved with AMI-LAZ as compared to osimertinib, with a median PFS of 23.7 versus 16.6 months in the respective groups (P<0.001).  There was also a significant PFS benefit of the combination over osimertinib in the high risk subgroups, including those with a history of brain metastases (31% improvement; P=0.01), those with liver metastases (42% improvement; P=0.017), those with an accompanying TP53 mutation (35% improvement; P=0.003) and those with detectable circulating tumor DNA at the start of treatment (32% improvement; P=0.002). Dr Salgia noted the positive results for the trial, and that the combination could become a preferred first line therapy for some EGFRm NSCLC patients, but also emphasized that AMI could lead to some significant side effects as a result of it being administered as an IV formulation.

PALOMA-3

Dr Salgia noted the availability of a SC formulation of AMI and the significant advantages of this formulation over the IV form in terms of ease of administration for the patients and reducing the overall workload to the oncology infusion clinic.  In PALOMA-3, patients had locally advanced or metastatic Ex19Del or L858R EGFRm NSCLC that had progressed following osimertinib or chemotherapy.  Patients in the trial received either the SC or IV formulations of AMI, both in combination with LAZ.  Results from the trial reported at ASCO 2024 showed a significant benefit of SC versus IV AMI for overall survival (OS), an exploratory endpoint (12-month OS, 65% versus 51%; P=0.02).  There was also a numerically longer duration of treatment response (11.2 vs. 8.3 months) and PFS (6.1 vs. 4.3 months) with the SC versus IV AMI formulation.  Importantly, however, Dr Salgia emphasized that immune-related adverse reactions (IRRs) were dramatically reduced with the SC versus IV AMI formulation (13% vs. 66%, 5-fold reduction), as was the frequency of blood clotting-related (venous thromboembolic) events (9% vs. 14%).  In addition, IRRs leading to a hospitalization, and IRRs leading to a treatment discontinuation were not observed in the SC arm but were observed in the IV arm of the study.  Overall, the results from PALOMA-3 demonstrated the SC formulation to be essentially equivalent (non-inferior) to the IV formulation of AMI in terms of efficacy when used as part of the AMI-LAZ combination, but the SC formulation was easier to administer, safer, and better tolerated.

Speaker Disclosure Information:

Dr Salgia did not report any relevant disclosures for this presentation.