AstraZeneca’s datopotamab deruxtecan (Dato-DXd), a cutting-edge TROP2-directed antibody-drug conjugate, has demonstrated encouraging overall survival results in the TROPION-Lung01 Phase III trial, which focused on patients with advanced nonsquamous non-small cell lung cancer (NSCLC). The study, conducted in collaboration with Daiichi Sankyo, compared datopotamab deruxtecan with docetaxel, the standard chemotherapy, revealing a median overall survival (OS) of 14.6 months for patients treated with datopotamab deruxtecan, compared to 12.3 months for those receiving docetaxel.

Key Findings from TROPION-Lung01 Phase III Trial

The TROPION-Lung01 trial is a global, multicenter, open-label study involving approximately 600 patients with advanced or metastatic NSCLC who had received at least one prior line of therapy. The trial’s dual primary endpoints were progression-free survival (PFS) and overall survival (OS). Datopotamab deruxtecan, developed by AstraZeneca and Daiichi Sankyo, targets TROP2-expressing cancer cells using a highly specialized antibody-drug conjugate designed to deliver a potent cytotoxic payload.

Although the overall survival data did not achieve statistical significance for the entire cohort, a clinically meaningful trend was observed in patients with nonsquamous NSCLC. For this subgroup, the median OS was 14.6 months with datopotamab deruxtecan versus 12.3 months with docetaxel, yielding a hazard ratio of 0.84 (95% CI 0.68-1.05). This trend underscores the potential benefit of datopotamab deruxtecan, particularly in the nonsquamous NSCLC subgroup.

Jacob Sands, MD, from Dana-Farber Cancer Institute and an investigator in the trial, noted the importance of these results. “Datopotamab deruxtecan’s trend towards improved overall survival, along with previously reported progression-free survival data, represents a significant advancement for patients with nonsquamous lung cancer,” he stated.

Safety Profile and Comparative Analysis

The safety profile of datopotamab deruxtecan was consistent with previous findings, demonstrating lower rates of dose reductions (20%) and discontinuations (8%) due to adverse events compared to docetaxel. The median treatment duration was significantly longer for datopotamab deruxtecan (4.2 months) versus docetaxel (2.8 months). Grade 3 or higher treatment-related adverse events included neutropenia, leukopenia, and interstitial lung disease (ILD). Notably, datopotamab deruxtecan showed a lower incidence of ILD compared to docetaxel.

These safety outcomes reinforce the potential of datopotamab deruxtecan as a viable treatment option, offering extended treatment duration with a manageable side effect profile.

NeoCOAST-2 Phase II Trial Results

In addition to the TROPION-Lung01 findings, results from the NeoCOAST-2 Phase II trial, presented at the WCLC Presidential Symposium, further highlight the potential of datopotamab deruxtecan. This trial evaluated the combination of datopotamab deruxtecan with Imfinzi (durvalumab) and carboplatin in early-stage resectable NSCLC. The combination demonstrated promising pathological complete response (pCR) and major pathological response (mPR) rates, with a pCR rate of 34.1% and an mPR rate of 65.9%.

The safety profile of this combination therapy was consistent with known profiles of the individual drugs, suggesting that datopotamab deruxtecan could be beneficial not only in advanced stages but also in earlier stages of NSCLC.

Future Directions and Ongoing Research

AstraZeneca and Daiichi Sankyo’s collaboration continues to advance datopotamab deruxtecan through a broad global clinical development program. This includes ongoing trials investigating its efficacy as a monotherapy and in combination with other treatments across various cancer types and stages. The results from TROPION-Lung01 and NeoCOAST-2 are expected to play a crucial role in shaping future research and regulatory submissions.

The TROPION-Lung01 trial, coupled with data from NeoCOAST-2, positions datopotamab deruxtecan as a promising new treatment option for patients with advanced nonsquamous NSCLC. While the overall survival benefit was not statistically significant in the entire trial cohort, the drug demonstrated a clinically meaningful improvement in specific subgroups. Datopotamab deruxtecan’s favorable safety profile and potential efficacy in both advanced and early-stage settings make it a noteworthy advancement in lung cancer treatment.

  advanced lung cancer treatment, AstraZeneca, Daiichi Sankyo, Datopotamab deruxtecan, NeoCOAST-2, NSCLC, Overall Survival, TROPION-Lung01