FDA Grants Accelerated Approval to T-DXd in Advanced HER2+ Solid Tumors

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Results from 3 DESTINY trials led to the accelerated approval of fam-trastuzumab deruxtecan-nxki for patients with unresectable or metastatic HER2-positive solid tumors.

Supporting data for the approval came from the DESTINY-PanTumor02 trial (NCT04482309), DESTINY-Lung01 trial (NCT03505710), and DESTINY-CRC02 trial (NCT04744831).

Supporting data for the approval came from the DESTINY-PanTumor02 trial (NCT04482309), DESTINY-Lung01 trial (NCT03505710), and DESTINY-CRC02 trial (NCT04744831).

Fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) has been granted accelerated approval by the FDA for patients with unresectable or metastatic HER2-positive solid tumors who have received prior systemic treatment and have no alternative therapy options.1

The approval is based on results from 3 trials in which 192 patients were enrolled: the phase 2 DESTINY-PanTumor02 trial (NCT04482309),2 the phase 2 DESTINY-Lung01 trial (NCT03505710),3 and the phase 2 DESTINY-CRC02 trial (NCT04744831).4 These trials excluded patients with interstitial lung disease/pneumonitis who needed steroids and those with significant cardiac disease. Additionally, if brain metastases were present and patients had an ECOG performance status of less than 1, they were not considered for the trial.

Major efficacy outcomes included a confirmed objective response rate (ORR) and duration of response (DOR) across all 3 trials. These outcomes were assessed by independent central review. For each trial, the rates were:

  • DESTINY-PanTumor02:
    • ORR was 51.4% (95% CI, 41.7%-61.0%)
    • Median DOR was 19.4 months
  • DESTINY-Lung01
    • ORR was 52.9% (95% CI, 27.8%-77.0%)
    • Median DOR was 6.9 months
  • DESTINY-CRC02
    • ORR was 46.9% (95% CI, 34.3%-59.8%)
    • Median DOR was 5.5 months

The most common adverse effects included decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, and fatigue.

The current recommended dosage of T-DXd is 5.4 mg/kg given intravenously every 3 weeks until disease progression or unacceptable toxicity.

References

  1. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors. News release. FDA. April 5, 2024. Accessed April 5, 2024. https://shorturl.at/hzLQ9
  2. Meric-Bernstam F, Makker V, Oaknin A, et al. Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-PanTumor02 phase II trial. J Clin Oncol. 2024;42(1):47-58. doi:10.1200/JCO.23.02005
  3. Smit EF, Felip E, Uprety D, et al. Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial. Lancet Oncol. 2024;25(4):439-454. doi:10.1016/S1470-2045(24)00064-0
  4. Raghav KPS, Siena S, Takashima A, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-overexpressing/amplified (HER2+) metastatic colorectal cancer (mCRC): primary results from the multicenter, randomized, phase 2 DESTINY-CRC02 study. J Clin Oncol. 2023;41(suppl 16). doi:10.1200/JCO.2023.41.16_suppl.3501

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