FDA Grants Accelerated Approval of Trastuzumab Deruxtecan for HER2-Positive Solid Tumors
On April 5, the US Food and Drug Administration granted accelerated approval to fam-trastuzumab deruxtecan-nxki (T-DXd) for patients with unresectable or metastatic HER2-positive (IHC3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options.
In a statement, the FDA said efficacy was evaluated in 192 adult patients with previously treated unresectable or metastatic HER2-positive solid tumors who were enrolled in one of three multicenter trials: DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. All three trials excluded patients with a history of interstitial lung disease/pneumonitis requiring treatment with steroids or interstitial lung disease/pneumonitis at screening and clinically significant cardiac disease. Patients were also excluded for active brain metastases or ECOG performance status >1. Treatment was administered until disease progression, death, withdrawal of consent, or unacceptable toxicity.1
The major efficacy outcome measure in all three trials was confirmed objective response rate (ORR), and an additional efficacy outcome was duration of response (DOR). In DESTINY-Lung01, ORR was 52.9% and median DOR was 6.9 months.1
According to the FDA, this tumor agnostic indication was approved under accelerated approval based on objective response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
China Accepts Application for Savolitinib in Previously Treated MET Exon 14 NSCLC
In late March, China’s National Medical Products Administration (NMPA) accepted a supplemental New Drug Application for savolitinib for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations, according to a press release from HUTCHMED, the maker of savolitinib. If approved, the label indication for savolitinib will be expanded to include treatment-naive patients in China.2
The application was based on phase IIIb data that demonstrated a median progression-free survival of 13.7 months. Median overall survival had not been reached in treatment-naïve patients when the final data from the confirmatory phase IIIb trial (NCT04923945) were presented on March 20 at the European Lung Cancer Congress. Preliminary efficacy and safety data from the first-line cohort of the trial were presented at the 2023 World Conference on Lung Cancer in September.2
Savolitinib was previously granted conditional approval in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.
The study data provide confirmatory evidence for savolitinib as a targeted treatment option for treatment-naïve or previously treated patients with MET exon 14 skipping alteration NSCLC. In treatment-naïve patients, objective response rate (ORR) was 62.1%, disease control rate (DCR) was 92.0% and median duration of response (DoR) was 12.5 months. Median progression-free survival (PFS) was 13.7 months and median overall survival (OS) was not reached with median follow-up of 20.8 months.3
In previously treated patients, ORR was 39.2%, DCR was 92.4%, and median DoR was 11.1 months. Median PFS was 11.0 months (95% CI: 8.3 months to 16.6 months) and median OS was not mature with median follow-up of 12.5 months.3
References
- 1. FDA grants accelerated approval to fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HER2-positive solid tumors
- 2. HUTCHMED Announces Savolitinib sNDA Accepted in China for Treatment-Naïve or Previously Treated Patients with Locally Advanced or Metastatic MET Exon 14 NSCLC
- 3. A phase IIIb study of savolitinib in patients with locally advanced or metastatic NSCLC harboring MET exon 14 mutation.
