Hot Topics in Lung Cancer

There are currently more than 800 clinical trials investigating treatments for lung cancer listed on NIH.

Healio has compiled a list of treatments in current and ongoing phase 2 and 3 studies to give a brief glance of where lung cancer research is heading.

Phase 2

Tepotinib (Tepmetko, Merck, EMD Serono) plus osimertinib (Tagrisso, AstraZeneca) in patients with EGFR-mutated, MET-amplified NSCLC

The Insight-2 study showed a 50% overall response rate for a combination of tepotinib and osimertinib in patients with EGFR-mutated, MET-amplified non-small cell lung cancer who have experienced disease progression after receiving osimertinib. The phase 2 study is assessing the combination’s efficacy and median duration as a second-line treatment.

Phase 3

Amivantamab (Rybrevant, Janssen) with lazertinib (Leclaza; Yuhan, Janssen Biotech) for EGFR-mutant NSCLC

Data from the randomized phase 3 MARIPOSA trial suggested that amivantamab, with or without the addition of lazertinib, improved PFS vs. chemotherapy alone in patients with EGFR-mutant NSCLC. The trial studied adults with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or L858R substitutions who experienced disease progression after or while receiving osimertinib.

Amivantamab plus chemotherapy for EGFR exon 20 insertion-mutated advanced NSCLC

The randomized phase 3 PAPILLON trial produced data indicating that amivantamab-vmjw along with chemotherapy improved PFS among patients with EGFR exon 20 insertion-mutated advanced NSCLC. The treatment had already received accelerated approval by the FDA in 2021 for patients whose disease progressed on or after platinum-based chemotherapy.

Neoadjuvant nivolumab (Opdivo, Bristol Myers Squibb) for resectable NSCLC

The double-blind CheckMate 77T trial was the first phase 3 study to examine the efficacy of a perioperative nivolumab-chemotherapy treatment for resectable NSCLC. The study produced data showing that nivolumab produced a 42% improvement in EFS compared with a placebo in a population of patients with EGFR/ALK wild-type disease and ECOG performance status of 0 or 1.

Adjuvant alectinib (Alecensa, Genentech) in ALK-positive early-stage lung cancer

The randomized phase 3 ALINA trial produced data showing that adjuvant therapy with alectinib showed positive PFS results compared with platinum-based chemotherapy in a population of patients with ALK-positive early-stage lung cancer. ALK-positive disease affects roughly 5% of patients with NSCLC.

References:

• Kim TM, et al. Tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification following 1L osimertinib: INSIGHT 2 primary analysis. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Sept. 9-12, 2023; Singapore.
• Janssen. Phase 3 MARIPOSA-2 Study meets dual primary endpoint resulting in statistically significant and clinically meaningful improvement in progression-free survival for RYBREVANT (amivantamab-vmjw) plus chemotherapy with and without lazertinib versus chemothery alone in patients with EGFR-mutated non-small cell lung cancer after disease progression on osimertinib (press release). Available at: https://www.jnj.com/phase-3-mariposa-2-study-meets-dual-primary-endpoint-resulting-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-for-rybrevant-amivantamab-vmjw-plus-chemotherapy-with-and-without-lazertinib-versus-chemotherapy-alone-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-after-disease-progression-on-osimertinib. Published Sept. 6, 2023. Accessed Oct. 27, 2023.
• Janssen. Treatment with RYBREVANT (amivantamab-vmjw) plus chemotherapy resulted in statistically significant and clinically meaningful improvement in progression-free survival in patients with newly diagnosed EGFR exon 20 insertion mutation-positive non-small cell lung cancer (press release). Available at: https://www.jnj.com/treatment-with-rybrevant-amivantamab-vmjw-plus-chemotherapy-resulted-in-statistically-significant-and-clinically-meaningful-improvement-in-progression-free-survival-in-patients-with-newly-diagnosed-egfr-exon-20-insertion-mutation-positive-non-small-cell-lung-cancer. Published July 17, 2023. Accessed Oct. 27, 2023.
• Cascone T, et al. Abstract LBA1. Presented at: European Society for Medical Oncology Congress; Oct. 20-24, 2023; Madrid.