The first patients with locally advanced or metastatic nonsquamous non-small cell lung cancer have been dosed in three phase 3 trials that will be assessing the safety and efficacy of datopotamab deruxtecan (Dato-DXd)-based combinations.
The three phase 3 trials are TROPION-Lung10, TROPION-Lung14 and TROPION-Lung15, according to a press release from Daiichi Sankyo, one of the developers of the drug.
Dato-DXd is a TROP2-directed antibody drug conjugate, according to the release. Note that the drug is being jointly developed with AstraZeneca. The release also mentioned that there at the moment, there are no antibody drug conjugates approved by the Food and Drug Administration that targets TROP2 to treat lung cancer.
“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,” Dr. Mark Rutstein, Global Head, Oncology Clinical Development at Daiichi Sankyo, said in the 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.”
Glossary:
Antibody drug conjugate: a substance consisting of a monoclonal antibody that is linked to a drug. The antibody binds to receptors or proteins found on cancer cells, and then the linked drug enters the cells and kills them while leaving surrounding cells intact.
Progression-free survival: the time during and after treatment when a patient with cancer lives without the disease worsening.
Overall survival: the time when a patient with cancer is still alive.
Overall response rate: the percentage of patients who have a partial response or a complete response to treatment.
In particular, TROPION-Lung10 is focusing on Dato-DXd plus rilvegostomig or rilvegostomig plus Keytruda (pembrolizumab) in patients with previously untreated, locally advanced or metastatic nonsquamous non-small cell lung cancer with a high PD-L1 expression and without actionable genomic alterations.
In TROPION-Lung14, patients with previously untreated, locally advanced or metastatic EGFR-mutated nonsquamous non-small cell lung cancer will be treated with either Dato-DXd plus Tagrisso (osimertinib) or Tagrisso alone.
Lastly, TROPION-Lung15 will aim to assess Dato-DXd with or without Tagrisso compared with a platinum-based doublet chemotherapy in locally advanced or metastatic nonsquamous, EGFR-mutated non-small cell lung cancer with disease progression on prior Tagrisso treatment.
“Clinical research suggests that combining an antibody drug conjugate with a targeted treatment or a bispecific immunotherapy may drive stronger and more durable tumor responses in patients with a variety of cancers including lung cancer,” Dr. Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer at AstraZeneca, said in the release. “The initiation of these additional three phase 3 trials of datopotamab deruxtecan in combination with our agents, [Tagrisso] and rilvegostomig, illustrates our commitment to exploring potential synergies within our oncology pipeline, as well as the full potential and combinability of this TROP2-directed antibody drug conjugate across multiple segments and settings of non-small cell lung cancer.”
TROPION-Lung10
In the TROPION-Lung10 trial, researchers will aim to enroll an estimated 675 patients with previously untreated, locally advanced or metastatic nonsquamous non-small cell lung cancer. Patients will be randomly assigned to receive Dato-DXd plus rilvegostomig, rilvegostomig alone or Keytruda alone. Researchers will focus on several areas of interest including progression-free survival and overall survival, in addition to objective response rate, duration of response, safety and tolerability.
The TROPION-Lung14 trial will enroll an estimated 580 patients with previously untreated, locally advanced or metastatic nonsquamous non-small cell lung cancer with an EGFR mutation, particularly exon 19 deletion and/or L858R, according to the release. Patients will be randomly assigned to treatment with Dato-DXd plus Tagrisso or Tagrisso alone. The areas of interest in this trial include progression-free survival, central nervous system progression-free survival, overall response rate, overall survival and safety.
In the TROPION-Lung15 trial, an estimated 630 patients will be randomly assigned to receive either Dato-DXdeither alone or with Tagrisso, or platinum-based doublet chemotherapy. Patients in this trial will have locally advanced or metastatic nonsquamous non-small cell lung cancer with at least one EGFR mutation, particularly G719X, exon 19 deletion, S768I, L858R and/or L861Q, and whose disease progressed after treatment with Tagrisso. The endpoints of interest include progression-free survival, central nervous system progression-free survival, overall response rate, overall survival, safety and duration of response.
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