FDA Approves Fam-Trastuzumab Deruxtecan-nxki for Unresectable or Metastatic HER2-Positive Solid Tumors


This is the fifth indication for fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo and AstraZeneca) approved by the FDA.

The FDA has expanded the approved indications for fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo and AstraZeneca) to include the treatment of adult patients with unresectable or metastatic HER2-positive (classified as immunohistochemistry [IHC] 3+) solid tumors who have received prior systemic treatment and who have no satisfactory alternative treatment options. The approval is based on data from the DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831) phase 2 trials, which included the evaluating of the therapy across HER2-positive (IHC 3+) metastatic solid tumors. However, due to the indication approval being under accelerated approval, ongoing approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Fam-trastuzumab deruxtecan-nxki, which is a HER2 directed antibody drug conjugate (ADC), is the first HER2-directed treatment to receive a tumor agnostic indication. The therapy now has 5 approved indications in the United States.

“This fifth indication in the US is a significant milestone as eligible patients with previously treated metastatic HER2 positive solid tumors may now be treated with [fam-trastuzumab deruxtecan-nxki],” said Ken Keller, global head of oncology business, and president and CEO, Daiichi Sankyo, Inc, in a press release. “The accelerated approval by the FDA for this tumor agnostic indication is based on the clinically meaningful efficacy seen with [fam-trastuzumab deruxtecan-nxki] across numerous types of metastatic cancers.”

Although HER2-directed therapies have been approved to treat breast, gastric, lung, and colorectal cancers, there are other HER2-positive metastatic solid tumors with limited or no treatment options available. For these solid tumors, HER2-positive expression classified as IHC 3+ has been observed as occurring at rates of approximately 28%.

“As the first antibody drug conjugate to be granted a tumor agnostic indication, [fam-trastuzumab deruxtecan-nxki] is truly delivering on its potential across metastatic HER2 targetable tumors,” said Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, in the press release. “This approval also elevates the importance of testing for biomarkers, including HER2, across a broad range of tumors to ensure these patients with advanced cancer who have few options know whether a targeted medicine might be right for them.”

In all the 3 phase 2 trials in the DESTINY clinical development program, the major efficacy outcome was objective response rate (ORR), and duration of response (DOR) was a secondary end point. In the DESTINY-PanTumor02 trial, investigators assessed efficacy among previously treated patients (n=111) with centrally or locally assessed HER2 positive solid tumors classified as IHC 3+, including either biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, or other tumors. In this trial, ORR was 51.4% (95% CI: 41.7-61.0) and median DOR was 19.4 months (range: 1.3, 27.9+).

In the DESTINY-Lung01 trial, investigators assessed efficacy looking at data from a subgroup of patients (n=17) with centrally confirmed HER2 positive non-small cell lung cancer classified as IHC 3+. The trials results confirmed an ORR of 52.9% (95% CI: 27.8-77.0) and a median DOR of 6.9 months (range: 4.0, 11.7+).

In DESTINY-CRC02, investigators assessed efficacy in patients (n=64) with centrally confirmed HER2 positive colorectal cancer classified as IHC 3+. Investigators observed an ORR of 46.9% (95% CI: 34.3-59.8) and a median DOR of 5.5 months (range: 1.3+, 9.7+).

“Until the approval of trastuzumab deruxtecan, patients with metastatic HER2 positive solid tumors have had limited treatment options,” said Funda Meric-Bernstam, MD, chair of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, in the press release. “Based on the clinically meaningful response rates seen across clinical trials, this tumor-agnostic approval means that patients may now be treated with a HER2-directed medicine.”


ENHERTU Approved in the U.S. as First Tumor Agnostic HER2 Directed Therapy for Previously Treated Patients with Metastatic HER2 Positive Solid Tumors. News Release. Tokyo: Daiichi Sankyo; April 5, 2024. Accessed April 6, 2024. https://daiichisankyo.us/press-releases/-/article/enhertu-approved-in-the-u-s-as-first-tumor-agnostic-her2-directed-therapy-for-previously-treated-patients-with-metastatic-her2-positive-solid-tumors

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