New BLA submitted to FDA for accelerated approval for datopotamab deruxtecan for NSCLC/EGFR

The companies have voluntarily withdrawn the BLA in the US for datopotamab deruxtecan for patients with advanced or metastatic nonsquamous NSCLC based on the TROPION-Lung01 Phase III trial. The decision to submit a new BLA for EGFR-mutated NSCLC and withdraw the previously submitted BLA for nonsquamous NSCLC was informed by feedback from the FDA.

The new BLA is based on results from the TROPION-Lung05 Phase II trial and supported by data from the TROPION-Lung01 Phase III and TROPION-PanTumor01 Phase I trials. New results from a pooled analysis of patients with previously treated EGFR-mutated NSCLC in the TROPION-Lung05 and TROPION-Lung01 trials will be featured in a late-breaking presentation at the upcoming European Society for Medical Oncology (ESMO) Asia 2024 Congress (LBA7).

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population. TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned Phase III lung cancer trials.”

Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “Treating EGFR-mutated non-small cell lung cancer is incredibly challenging following disease progression given that the complexity and variability of these mutations often lead to resistance. The potential approval of datopotamab deruxtecan could offer renewed hope for patients with this formidable disease.”

Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.

AstraZeneca and Daiichi Sankyo are evaluating datopotamab deruxtecan alone and with Tagrisso (osimertinib) as treatment for patients with advanced or metastatic EGFR-mutated nonsquamous NSCLC in the ongoing TROPION-Lung14 and TROPION-Lung15 Phase III trials. In addition, ongoing Phase III trials in 1st-line advanced or metastatic nonsquamous NSCLC, AVANZAR and TROPION-Lung10, have the potential to validate the QCS (quantitative continuous scoring) biomarker for TROP2 identified in an exploratory analysis of TROPION-Lung01. An additional trial in patients with biomarker-positive tumours in the 2nd-line nonsquamous NSCLC setting is also planned.

TROPION-Lung05; TROPION-Lung05 is a global, multicentre, single-arm, open-label Phase II trial evaluating the efficacy and safety of datopotamab deruxtecan in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on or after one regimen of platinum-based chemotherapy and at least one TKI (with or without other systemic therapies). Patients receiving up to four prior lines of treatment with tumours with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial. The primary trial endpoint of TROPION-Lung05 is objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary efficacy endpoints include duration of response (DoR), disease control rate (DCR), clinical benefit rate, progression-free survival (PFS), time to response (TTR), overall survival (OS) and safety. TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America.

TROPION-PanTumor01; TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with NSCLC to assess the safety and tolerability of datopotamab deruxtecan to determine the recommended dose for expansion (6 mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-low or negative breast cancer, SCLC, urothelial, gastric, pancreatic, castration-resistant prostate and esophageal cancer. Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.