First Patients Dosed in New Phase 3 Trials of Dato-DXd in NSCLC

Holographic concept of lung cancer: © catalin - stock.adobe.com

The first patients have been dosed in 3 phase 3 trials evaluating various combinations of datapotamab deruxtecan (Dato-DXd) for the treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC).¹

TROPION-Lung10 (NCT06357533) is investigating Dato-DXd plus rilvegostomig (AZD2936), a PD-1/TIGIT bispecific antibody, or rilvegostomig alone vs pembrolizumab (Keytruda) in patients with treatment-naive, locally advanced or metastatic, nonsquamous NSCLC with high PD-L1 expression and without actionable gene alterations.

TROPION-Lung14 (NCT06350097) will look at Dato-DXd plus osimertinib (Tagrisso) vs osimertinib alone in patients with previously untreated, locally advanced or metastatic EGFR-mutated nonsquamous NSCLC.

In TROPION-Lung15 (NCT06417814), investigators will assess Dato-DXd with or without osimertinib vs platinum-based doublet chemotherapy for the treatment of patients with locally advanced or metastatic, nonsquamous NSCLC with an EGFR mutation and whose disease progressed on osimertinib.

“These three trials in either high PD-L1 expressing or EGFR-mutated nonsquamous non–small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer,” said Mark Rutstein, MD, global head of oncology clinical development, Daiichi Sankyo, said in a press release. “Our growing TROPION clinical program, which now consists of seven phase 3 trials demonstrates our commitment to understanding the full potential of datopotamab deruxtecan in lung cancer.”

The FDA is considering the biologics license application of Dato-DXd in patients with previously treated advanced nonsquamous NSCLC supported by data from TROPION-Lung01 (NCT04656652), and a Prescription Drug User Fee Act target action date of December 20, 2024, is planned.²

About TROPION-Lung10

TROPION-Lung10 plans to enroll an estimated 675 patients and randomize them to receive Dato-DXd plus rilvegostomig, rilvesgostomig monotherapy, or pembrolizumab. The agents will be administered intravenously (IV) on day 1 of 21-day cycles.³

The study’s primary end points are progression-free survival (PFS) and overall survival (OS) in TROP2 biomarker-positive patients, and secondary end points include PFS in the intent-to-treat (ITT) population, OS in the ITT population, objective response rate (ORR), duration of response (DOR), patient-reported lung cancer symptoms, patient-reported physical functioning, pharmacokinetics (PK), and second PFS (PFS2).

About TROPION-Lung14

TROPION-Lung14 plans to enroll an estimated 582 patients with NSCLC harboring an EGFR exon 19 deletion and/or L858R mutation. Patients will be randomized to receive oral osimertinib 80 mg daily plus Dato-DXd IV on day 1 of 21-day cycles or oral osimertinib monotherapy.⁴

The study’s primary end point is PFS by blinded independent central review, and secondary end points include OS, central nervous system (CNS) PFS, ORR, DOR, PFS2, and PK.

About TROPION-Lung15

An estimated 630 patients will be enrolled in TROPION-Lung15 and will be randomized 1:1:1 to receive Dato-DXd plus osimertinib, Dato-DXd, or a chemotherapy doublet of pemetrexed plus carboplatin or cisplatin. Dato-DXd will be administered on day 1 of a 21-day cycle, osimertinib 80 mg will be administered orally daily, and chemotherapy will be administered every 3 weeks for 4 cycles.⁵

The study’s primary end point is PFS, and secondary end points include OS, CNS PFS, ORR, DOR, PFS2, ORR, quality of life, and PK.

REFERENCES:

1. Three phase 3 trials of datopotamab deruxtecan-based combinations initiated in patients with advanced nonsquamous non-small cell lung cancer. News release. Daichii Sankyo. October 30, 2024. Accessed October 31, 2024. https://tinyurl.com/59k6adc8

2. Datopotamab deruxtecan biologics license application accepted in the US for patients with previously treated advanced nonsquamous non-small cell lung cancer. News release. AstraZeneca. February 19, 2024. Accessed October 31, 2024. https://tinyurl.com/w595xw6u

3. Phase III, open-label, study of first-line dato-dxd in combination with rilvegostomig for advanced non-squamous NSCLC with high PD-L1 Expression (TC ≥ 50%) and without actionable genomic alterations (TROPION-Lung10). ClinicalTrials.gov. Updated June 14, 2024. Accessed October 31, 2024. https://www.clinicaltrials.gov/study/NCT06357533

4. Phase III, open-label study of first-line osimertinib with or without datopotamab deruxtecan for EGFRm locally advanced or metastatic non-small cell lung cancer (TROPION-Lung14). ClinicalTrials.gov. Updated October 26, 2024. Accessed October 31, 2024. https://www.clinicaltrials.gov/study/NCT06350097

5. Study to investigate the efficacy and safety of dato-dxd with or without osimertinib compared with platinum based doublet chemotherapy in participants with EGFR-mutated locally advanced or metastatic non-small cell lung cancer (TROPION-Lung15). ClinicalTrials.gov. Updated October 26, 2024. Accessed October 31, 2024. https://www.clinicaltrials.gov/study/NCT06417814