Aaron Lisberg, MD, reviews data from the TROPION-Lung01 study investigating Dato-DXd in previously treated patients with advanced/metastatic NSCLC.

Dato-DXd vs Docetaxel in Previously Treated Advanced/Metastatic Non–Small Cell Lung Cancer: Results of the Randomized Phase III Study TROPION-Lung01

Dato-DXd is a novel TROP2-directed antibody-drug conjugate under clinical investigation in multiple tumor types.

This is the first report of TROPION-Lung01 (NCT04656652), a randomized, global, open-label, phase 3 study of Dato-DXd vs docetaxel (DTX) in pretreated patients (pts) with adv/met NSCLC with or without actionable genomic alterations (AGAs).

Pts were randomized 1:1 to Dato-DXd 6 mg/kg or DTX 75 mg/m2 Q3W.

Dual primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR]) and overall survival (OS).

Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety.

604 pts were included in the full analysis set (FAS); 43.1% had received ≥2 prior lines of systemic therapy.

PFS was significantly improved with Dato-DXd over DTX in the FAS (HR, 0.75; 95% CI, 0.62-0.91; P=.004; median, 4.4 vs 3.7 mo).

Confirmed ORRs were 26.4% (Dato-DXd) and 12.8% (DTX), with median DORs of 7.1 and 5.6 mo.

Longer median PFS was observed in the prespecified non-squamous histology subgroup (NSQ; 5.6 vs 3.7 mo).

Median treatment duration was 4.2 mo (range, 0.7-18.3 mo) for Dato-DXd and 2.8 mo (range, 0.7-18.9 mo) for DTX.

The most common treatment-emergent adverse events (TEAEs) seen with Dato-DXd were stomatitis (49.2%, mostly grade [gr] 1/2) and nausea (37%).

Adjudicated drug-related interstitial lung disease gr ≥3 occurred in 3.4% of pts with Dato-DXd vs 1.4% with DTX.

Fewer drug-related gr ≥3 TEAEs and AEs leading to dose reduction or discontinuation were seen with Dato-DXd vs DTX.

PFS was significantly improved with Dato-DXd over DTX in pts with pretreated adv/met NSCLC.

NSQ patients appeared to derive the most benefit.

Dato-DXd was well tolerated, with a manageable safety profile.

The trial is continuing until the final OS analysis.

Ahn M, Lisberg AE, Paz-Ares L et al. LBA12 - Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01. Abstract presented at: ESMO Congress 2023, October 20-24, 2023.

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Aaron Lisberg, MD, assistant professor of medicine, hematologist, thoracic medical oncologist, University of California, Los Angeles (UCLA) Health, discusses ongoing and future efforts to expand effective treatment options for patients with osimertinib (Tagrisso)-resistant, 

mutant non–small cell lung cancer (NSCLC).

The phase 1 Chrysalis-2 trial (NCT04077463) is evaluating the use of the EGFR TKI lazertinib (Laclaza) alone and in combination with the bispecific antibody amivantamab-vmjw (Rybrevant) for patients with 

-mutant NSCLC. Those patients who progressed on prior treatment with osimertinib and platinum-based chemotherapy were enrolled to cohort A of the dose-expansion portion of the study.

Updated results from cohort A were previously presented at the 2022 ASCO Annual Meeting, and they showed that the combination of lazertinib plus amivantamab produced an overall response rate of 33% (95% CI, 26%-41%) and a median duration of response of 9.6 months (95% CI, 7.0–not evaluable) in these patients, who harbored 

 exon 19 deletions or L858R mutations. The safety profile of this regimen was also consistent with prior reports, and these data support the continued exploration of the combination in a larger patient population, Lisberg says.

Other emerging agents in the post-osimertinib space include the antibody-drug conjugates patritumab deruxtecan (HER3-DXd) and datopotamab deruxtecan (Dato-DXd; DS-1062a), Lisberg continues.

-mutant NSCLC after osimertinib progression, making this target a viable candidate for exploration, Lisberg states. In a phase 1 trial (NCT03260491) of previously treated patients with 

-mutated metastatic or unresectable NSCLC, HER3-DXd was shown to generate responses and be well-tolerated.

Meanwhile, the TROP-2 targeted agent Dato-DXd is currently being explored in patients who have NSCLC with or without actionable genomic alterations, Lisberg continues. Current data indicate that the agent has shown efficacy in both populations, he adds. Findings previously presented at the 2021 ESMO Congress from the phase 1 TROPION-PanTumor01 trial (NCT03401385) highlighted the agent's promising response rate and safety in patients with NSCLC harboring genetic alterations, including 

Future data will hopefully continue to support the viability of these novel strategies for patients with NSCLC and acquired osimertinib resistance, Lisberg concludes.

 Dr Lisberg reported receiving consultant/advisory board fees from AstraZeneca, Bristol Myers Squibb, Leica Biosystems, Jazz Pharmaceuticals, Novocure, Pfizer, MorphoSys, Eli-Lilly, Oncocyte, Novartis, Regeneron, Janssen Incology, and Sanofi; commercial research grants from Daiichi Sankyo, Calithera Biosciences, AstraZeneca, Dracen Pharmaceuticals, WindMIL, and eFFECTOR Therapeutics; and employment and equity interest from Boston Scientific.

Aaron Lisberg, MD, discusses ongoing and future efforts to expand effective treatment options for patients with osimertinib-resistant, EGFR-mutant non–small cell lung cancer.

Aaron Lisberg, MD

Articles

Dato-DXd vs Docetaxel in Previously Treated Advanced/Metastatic Non–Small Cell Lung Cancer: Results of the Randomized Phase III Study TROPION-Lung01

Dr Lisberg on Emerging Post-Osimertinib Treatment Options in EGFR-mutant NSCLC