Top 10 Lung Cancer Advances of 2024

Significant advancements in lung cancer treatment were seen throughout 2024, from new drug approvals to promising clinical trial results. Here are some of the top developments covered by Targeted Oncology^TM, highlighting the progress in targeted therapies and improved patient outcomes.

FDA Approval of Ensartinib for ALK-Positive NSCLC: The FDA approved ensartinib for the first-line treatment of patients with ALK-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who have not previously received an ALK inhibitor. This decision was supported by findings from the phase 3 eXalt3 trial (NCT02767804), which demonstrated a median progression-free survival (PFS) of 25.8 months with ensartinib compared with 12.7 months with crizotinib (Xalkori).

FDA Approves Tarlatamab in Small Cell Lung Cancer: In May 2024, the FDA granted accelerated approval to tarlatamab-dlle (Imdelltra), a bispecific T-cell engager (BiTE), for small cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy, based on results from the phase 2 DeLLphi-301 study (NCT05060016). This approval makes tarlatamab the first BiTE therapy approved for a major solid tumor.

FDA Complete Response Letter for SC Amivantamab BLA in EGFR+ NSCLC: The FDA issued a complete response letter (CRL) for the biologics license application (BLA) for subcutaneous amivantamab-vmjw (Rybrevant) with recombinant human hyaluronidase, covering all approved or submitted indications for intravenous amivantamab in select patients with NSCLC. According to Johnson & Johnson, the CRL pertains to manufacturing inspection issues, not the product’s formulation, efficacy, safety, or the need for additional clinical studies.

Amivantamab Boosts OS in EGFR-Mutant NSCLC After Osimertinib: Longer-term follow-up from the MARIPOSA-2 trial (NCT04988295) continues to demonstrate improved overall survival (OS) with amivantamab combined with chemotherapy compared with chemotherapy alone in patients with EGFR-mutant advanced NSCLC who experienced disease progression on osimertinib (Tagrisso). These findings, based on a median follow-up of 18.1 months, were presented at the 2024 ESMO Congress.

FDA ODAC Unanimously Calls for Phase Assessments in NSCLC Perioperative Regimens: In a unanimous 11 to 0 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) recommended that the FDA require new trial designs for perioperative regimens in resectable NSCLC to include thorough assessments of the contribution of each treatment phase.

FDA Grants Full Approval to Tepotinib in NSCLC: In February 2024, tepotinib (Tepmetko) was FDA-approved for patients with NSCLC with mesenchymal-epithelial transition (MET) exon 14 skipping alterations. The approval was supported by findings from the VISION trial (NCT02864992).

FDA Grants Zongertinib Breakthrough Designation in HER2-Mutant NSCLC: Zongertinib (BI 1810631), an investigational oral therapy, received breakthrough therapy designation from the FDA in August 2024. The agent also received breakthrough therapy designation from China’s Center for Drug Evaluation for adult patients with advanced, unresectable or metastatic NSCLC with activating HER2 mutations.

New BLA Submitted for Dato-DXD in EGFR-Mutant NSCLC: A new BLA was submitted specifically for EGFR-mutated NSCLC after FDA feedback, replacing the earlier nonsquamous NSCLC application. This application draws from phase 2 and phase 3 data in the TROPION-Lung01 (NCT04656652), TROPION-Lung05 (NCT04484142), and TROPION-PanTumor01 (NCT03401385) trials.

Osimertinib Improves PFS in Stage III EGFR+ NSCLC: Osimertinib demonstrated statistically significant and clinically meaningful improvements in PFS for the treatment of unresectable, stage III EGFR-mutant NSCLC following chemoradiotherapy, compared with placebo, according to results from the phase 3 LAURA trial (NCT03521154). This marks the first EGFR inhibitor and targeted therapy to show PFS benefits in patients with stage III disease.

FLAURA2 Analysis Extends Osimertinib Combo Benefit in NSCLC: The second interim analysis of the phase 3 FLAURA2 study (NCT04035486) showed encouraging trends for osimertinib combined with platinum-pemetrexed chemotherapy over osimertinib monotherapy in EGFR-mutant advanced NSCLC. The combination arm had a median OS not reached vs 36.7 months with osimertinib alone (HR, 0.75; P = .028), and also showed favorable outcomes for post-progression measures.

These developments represent significant strides in lung cancer research and treatment, offering hope for improved patient outcomes and survival rates.