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REJOICE-Ovarian01 — Raludotatug deruxtecan (R-DXd, CDH6 ADC) in platinum-resistant ovarian

Abstract: Phase 2/3 efficacy readout · Session: Saturday April 11, 2026 · Simultaneous publication: TBD (Gynecologic Oncology abstract + Daiichi data package)

Headline: First CDH6-targeted ADC clinical efficacy at scale — ORR 50.5% in platinum-resistant high-grade serous/endometrioid ovarian cancer, establishing CDH6 as a tractable ovarian ADC target beyond FRα.

At a glance

  • Sponsor: Daiichi Sankyo (R-DXd / DS-6000)
  • PI / presenter: Apr 11 presentation (presenter TBD)
  • NCT ID: NCT05489211 (REJOICE-Ovarian01)
  • Phase / arms / N: Phase 2/3, multi-dose-cohort expansion in platinum-resistant ovarian
  • Primary endpoint(s): ORR (RECIST 1.1)
  • Indication / line: Platinum-resistant high-grade serous or endometrioid ovarian cancer
  • Comparator: None at Ph2 (Ph3 expansion vs investigator-choice chemo planned)
  • Session: Day 2 (Apr 11)

Headline result

Confirmed ORR 50.5% overall in platinum-resistant HGSOC/endometrioid — a roughly 5x lift over the ~10% ORR historical benchmark of single-agent chemo in this setting. CDH6 expression by IHC was correlated with response. Safety profile consistent with the deruxtecan (DXd) topo-1 ADC class — ILD/pneumonitis remains the watched AE.

Mechanism / class

Raludotatug deruxtecan (R-DXd, DS-6000) is an antibody-drug conjugate targeting CDH6 (cadherin-6) — a kidney- and ovarian-restricted target — with the Daiichi DXd exatecan-derivative topoisomerase-1 payload (same payload class as trastuzumab deruxtecan / datopotamab deruxtecan / patritumab deruxtecan). First CDH6 ADC to deliver clinical efficacy at scale.

Trial design deep dive

Study architecture: Phase 2/3 seamless design — Phase 2 portion is multi-dose-cohort expansion (specific doses TBD per Daiichi protocol, typically 4.8 mg/kg, 5.6 mg/kg, and 6.4 mg/kg Q3W for the DXd class) in platinum-resistant HGSOC/endometrioid ovarian cancer; Phase 3 portion will randomize R-DXd vs investigator-choice chemo (paclitaxel, PLD, or topotecan). Enrollment open to platinum-resistant high-grade serous or endometrioid histology; CDH6 IHC selection strategy TBD (prospective vs retrospective stratification).

Endpoint definitions: Phase 2 primary endpoint ORR by blinded independent central review per RECIST 1.1. Secondary endpoints include DOR, PFS, OS, safety, and PK. Phase 3 primary endpoint expected to be PFS with OS as key secondary (gated). The 50.5% confirmed ORR reported at SGO 2026 is the Phase 2 efficacy readout.

Key subgroup analyses: CDH6 IHC expression-by-response correlation — the most-watched analysis, with response correlated to expression per the OncLive coverage. Histology (HGSOC vs endometrioid), prior bevacizumab exposure, prior PARPi, and dose-cohort subgroups TBD in full presentation. ILD/pneumonitis rates by dose cohort are the safety-side counterpart.

Comparator context: No randomized control in Phase 2, but the 50.5% ORR represents a ~5x lift over the ~10% historical chemo benchmark in platinum-resistant HGSOC. Phase 3 investigator-choice chemo arm will provide the formal comparison.

FDA implications: Pre-pivotal — Phase 2 establishes CDH6 ADC efficacy clinically; Phase 3 expansion (already enrolling per the seamless design) is the registration vehicle. Project Optimus dose-optimization will apply across the DXd-platform comparison.

Discussant takeaway

Per OncLive coverage: the 50.5% ORR is the first robust signal that the deruxtecan platform extends beyond HER2 and TROP2 into a kidney/ovarian-restricted target — and that platinum-resistant ovarian, long stuck near 10% ORR with chemo, can be reshaped by ADCs alongside the FRα franchise.

Practice-changing verdict

No (Ph2/3 readout) — but pivotal-design-defining. REJOICE-Ovarian01 anchors a registration-enabling Phase 3 expansion. Class-level read-through across the DXd ovarian platform (datopotamab, patritumab) and across CDH6 in renal.

  • AACR 2026: CDH6 mechanism + deruxtecan-platform sessions (Apr 17–22)
  • Other SGO 2026: Mirvetuximab IMGN853-0420 (FRα ADC); BLUESTAR puxitatug samrotecan (B7-H4); BNT-324 (B7-H3); BEHOLD-1
  • ASCO 2026: Expected dose-cohort comparisons + tolerability deep-dive
  • ESMO 2026: Mature R-DXd follow-up
  • JPM 2026: Daiichi Sankyo DXd-platform framing Jan 12–15

Sources