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

News
Article

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

Recent Videos
According to John Henson, MD, “What we need are better treatments to control the [brain] tumor once it’s detected.”
First-degree relatives of patients who passed away from pancreatic cancer should be genetically tested to identify their risk for the disease.
Destigmatizing cancer care for incarcerated patients may help ensure that they feel supported both in their treatment and their humanity.
A lower percentage of patients who were released within 1 year of incarceration received guideline-concurrent care vs incarcerated patients.
A collaboration between the Connecticut Departments of Health and Corrections and the COPPER Center aimed to improve outcomes among incarcerated patients.
Computational models help researchers anticipate how ADCs may behave in later lines of development, while they are still in the early stages.
ADC payloads with high levels of potency can sometimes lead to higher levels of toxicity, which can eliminate the therapeutic window for patients with cancer.
According to Greg Thurber, PhD, target-mediated uptake is the biggest driver of efficacy for antibody-drug conjugates as a cancer treatment.
Co-hosts Kristie L. Kahl and Andrew Svonavec highlight what to expect at the 43rd Annual Chemotherapy Foundation Symposium, such as new chemotherapeutics and targeted therapies.
In neuroendocrine tumor management, patients with insulinoma may be at risk of severe hypoglycemia following receipt of GLP-1 receptor agonists.
Related Content
Rising cancer diagnoses in the US highlight urgent needs for improved oncology education, workforce distribution, and care infrastructure, especially in rural areas.

A Decline in the US Oncology Workforce: What Will the Next Decade Bring?

Julie M. Vose, MD, MBA
December 2nd 2025
Article

Rising cancer diagnoses in the US highlight urgent needs for improved oncology education, workforce distribution, and care infrastructure, especially in rural areas.

Decision-Making Capacity: The Ethical Core of Patient-Centered Oncology

Decision-Making Capacity: The Ethical Core of Patient-Centered Oncology

Daniel C. McFarland, DO;Louis P. Voigt, MD;Yesne Alici, MD
November 24th 2025
Podcast

Daniel C. McFarland, DO, is joined by Louis P. Voigt, MD, and Yesne Alici, MD, who focused on decision-making capacity and patient-centered care.

PAS-004 was deemed safe and tolerable when given in 37 mg capsules, so the trial will proceed to administer the agent in 45 mg capsules.

Cohort 7 of Novel MEK Inhibitor Trial Completed for MAPK Pathway-Driven Tumors

Tim Cortese
November 25th 2025
Article

PAS-004 was deemed safe and tolerable when given in 37 mg capsules, so the trial will proceed to administer the agent in 45 mg capsules.

Experts discussed supportive care and why it should be integrated into standard oncology care.

How Supportive Care Methods Can Improve Oncology Outcomes

Declan Walsh, MD;Denise B. Reynolds, RD;Adam Friedman, MD, FAAD;Daniel C. McFarland, DO;Michelle Fingeret, PhD;Christian J. Nelson, PhD;William S. Breitbart, MD
November 10th 2025
Podcast

Experts discussed supportive care and why it should be integrated into standard oncology care.

Novel Agent Yields Promising Results in MAPK-Associated Solid Tumors

Novel Agent Yields Promising Results in MAPK-Associated Solid Tumors

Ariana Pelosci
November 21st 2025
Article

Partial responses and stable disease were observed with PAS-004 in patients with advanced solid tumors harboring RAS, NF1, or RAF mutations.

Results from the C-POST trial showed that cemiplimab improved DFS vs placebo in patients with CSCC at high risk of recurrence following surgery and radiation.

EC Approves Adjuvant Cemiplimab in CSCC at High Risk of Recurrence

Tim Cortese
November 20th 2025
Article

Results from the C-POST trial showed that cemiplimab improved DFS vs placebo in patients with CSCC at high risk of recurrence following surgery and radiation.