Daiichi Sankyo and Merck & Co. have withdrawn an antibody-drug conjugate (ADC) filing after the FDA said they lacked the data for accelerated approval in a lung cancer population.
The partners filed for accelerated approval of their B7-H3-directed ADC, ifinatamab deruxtecan (I-DXd), based on data from the phase 2 IDeate-Lung01 study. The clinical trial enrolled 187 participants with extensive-stage small cell lung cancer (ES-SCLC) who were previously treated with at least one prior line of platinum-based chemotherapy. Researchers called the phase 2 efficacy “promising.”
However, the FDA told Daiichi and Merck that the data supporting the application falls short of the level needed to meet the requirements for accelerated approval. In response, the partners voluntarily pulled the filing for accelerated approval in ES-SCLC that progressed on or after platinum-based chemotherapy.
Merck is “disappointed that the current dataset are not supportive of an approval at this time,” Marjorie Green, M.D., head of oncology, global clinical development at Merck Research Laboratories, said in a statement. But with enrollment in the phase 3 IDeate-Lung02 trial nearing completion, the partners may return to the FDA with an expanded dataset in the future.
The withdrawal has potential implications for Amgen and GSK. Amgen sells a DLL3xCD3 T-cell engager, Imdelltra, for ES-SCLC patients who progress on platinum-based chemotherapy. GSK is developing a rival B7-H3-directed ADC, risvutatug rezetecan, which recently impressed in a phase 3 trial in China.
Phase 3 trials in castration-resistant prostate cancer and esophageal squamous cell carcinoma give I-DXd other paths to market. Even so, the withdrawal of the ES-SCLC filing represents another blow to a deal that has disappointed to date.
Merck paid Daiichi $4 billion upfront in 2023 to partner on three ADCs. The FDA rejected a request for approval of one of the ADCs, the HER3-directed asset patritumab deruxtecan (HER3-DXd), in 2024 on manufacturing grounds. The next year, Daiichi and Merck voluntarily withdrew a HER3-DXd submission after failing to show improved overall survival.
The partners continued to test HER3-DXd, including in an ongoing phase 3 breast cancer trial, but shifted their hopes for near-term sales to I-DXd. The I-DXd withdrawal pushes back the timeline for generating a return on the ADC. Phase 3 trials of I-DXd in ES-SCLC, prostate cancer and esophageal squamous cell carcinoma have primary completion dates in 2028, according to the federal trials database.
Raludotatug deruxtecan (R-DXd), a CDH6-directed ADC, is the third asset covered by the deal. A phase 2/3 trial of R-DXd in ovarian cancer has a primary completion date of February 2028 on the trials register.