Sponsor: Merck Sharp & Dohme LLC (industry)
Phase: 3
Start date: May 13, 2025
Planned enrollment: 1440
Ifinatamab deruxtecan (I-DXd; DS-7300; MK-2400) is an investigational B7-H3–directed antibody–drug conjugate (ADC) from Daiichi Sankyo and Merck. It has shown antitumor activity across several solid tumors, with the most mature results in previously treated extensive-stage small cell lung cancer (ES‑SCLC). I-DXd received U.S. FDA Breakthrough Therapy Designation on August 18, 2025 for ES‑SCLC after platinum-based chemotherapy, supported by the phase 2 IDeate‑Lung01 trial. Phase 3 trials are ongoing in relapsed SCLC (IDeate‑Lung02) and in metastatic castration‑resistant prostate cancer (IDeate‑Prostate01). Press release (FDA BTD); WCLC 2025 IASLC news; JCO phase 3 SCLC trial-in-progress abstract; Phase 3 prostate cancer study initiation. (daiichisankyo.us)
Small cell lung cancer (SCLC)
Other tumors (phase 1/2, multi‑cohort; updated ESMO 2023 abstract 690P)
Ongoing confirmatory development
Notes - Reported results are from conference presentations and company/medical‑society communications through September 2025; peer‑reviewed, full‑text clinical publications for the phase 2 SCLC dataset were not identified at the time of this summary. (iaslc.org)
Last updated: Oct 2025
Goal: Evaluate whether ifinatamab deruxtecan (I-DXd, MK-2400) improves overall survival and radiographic progression-free survival versus docetaxel in metastatic castration-resistant prostate cancer (mCRPC).
Patients: Adults with mCRPC with progression on androgen deprivation therapy or post-orchiectomy within 6 months, previously treated with 1–2 androgen receptor pathway inhibitors for at least 8 weeks, and no prior taxane for mCRPC. Key exclusions include prior steroid-requiring interstitial lung disease/pneumonitis, uncontrolled or significant cardiovascular disease, and prior taxane in the mCRPC setting.
Design: Global, randomized, open-label, active-controlled phase 3 trial comparing I-DXd to docetaxel. Blinded independent central review is used for radiographic endpoints. Planned enrollment is large to power co-primary OS and rPFS analyses.
Treatments: I-DXd: 12 mg/kg intravenously every 3 weeks. Ifinatamab deruxtecan is an antibody–drug conjugate targeting B7-H3 (CD276), a transmembrane protein highly expressed across many solid tumors with low expression in normal tissue. The humanized IgG1 antibody is linked via a cleavable tetrapeptide linker to a topoisomerase I inhibitor payload (DXd), designed to deliver cytotoxic payload selectively to tumor cells. In pretreated extensive-stage small cell lung cancer, I-DXd has shown objective response rates around 50% at the 12 mg/kg dose with median PFS approximately 5–6 months and OS around 12 months, with key toxicities including gastrointestinal and hematologic events and a risk of ILD/pneumonitis in roughly 9–12%. Docetaxel: 75 mg/m2 IV every 3 weeks plus daily prednisone per label, a standard chemotherapy option for mCRPC after ARPI exposure.
Outcomes: Co-primary endpoints are overall survival and radiographic progression-free survival by PCWG-modified RECIST 1.1 assessed by blinded independent central review. Secondary endpoints include time to first subsequent therapy, objective response rate, duration of response, time to pain progression, time to PSA progression, PSA response rate, time to first symptomatic skeletal-related event, incidence of adverse events, and treatment discontinuations due to adverse events.
Burden on patient: Moderate. As a phase 3 study with IV therapy every 3 weeks, participants will have regular clinic visits for infusions, routine labs, adverse event monitoring, and periodic radiographic assessments consistent with mCRPC standards. The investigational arm may require additional pulmonary monitoring given ILD/pneumonitis risk, but there is no indication of intensive pharmacokinetic sampling or mandatory serial biopsies. Travel and time commitments are comparable to standard chemotherapy schedules, with added vigilance for respiratory symptoms and standard imaging frequency for rPFS evaluations.
Last updated: Oct 2025
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has diagnosis of metastatic castration-resistant prostate cancer (mCRPC)
* Has prostate cancer progression while on androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months prior to entering the study
* Has received prior treatment with 1 or 2 androgen receptor pathway inhibitor (ARPI) and progressed during or after at least 8 weeks of treatment
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids
* Has uncontrolled or significant cardiovascular disease
* Has received prior treatment with a taxane-based chemotherapy agent for mCRPC
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