Half of platinum-resistant ovarian cancer patients respond to Raludotatug deruxtecan in REJOICE-Ovarian01 trial

Raludotatug deruxtecan delivers high response rates in a difficult-to-treat ovarian cancer population

A major breakthrough has emerged in the long-standing challenge of managing platinum-resistant ovarian cancer. In the phase 2 portion of the ongoing REJOICE-Ovarian01 global trial, Raludotatug deruxtecan — an antibody-drug conjugate (ADC) developed jointly by Daiichi Sankyo Company, Limited and Merck & Co., Inc. — produced a confirmed objective response rate (ORR) of 50.5 percent among patients with recurrent platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer.

The study enrolled 107 patients who had previously undergone multiple lines of treatment — a population historically characterized by low survival rates and poor therapeutic options. Data presented by the developers indicated that the responses included both complete and partial remissions across all dose levels tested, underscoring clinically meaningful efficacy in a setting where standard chemotherapy typically yields ORRs below 15 percent.

Investigators described the results as a significant advance in the ADC field, particularly given the inclusion of patients pretreated with both bevacizumab and PARP inhibitors, two therapies that often limit subsequent response potential.

How the REJOICE-Ovarian01 phase 2 data set a new benchmark for efficacy and safety in resistant disease

According to information released by the companies, participants received Raludotatug deruxtecan at doses of 4.8 mg/kg, 5.6 mg/kg, or 6.4 mg/kg. Across the total population, three patients achieved complete responses and 51 achieved partial responses, translating to an overall disease control rate (DCR) of 77.6 percent. Median time to response was approximately seven weeks, signaling a rapid onset of activity rarely seen in this tumor type.

At the 5.6 mg/kg dose — selected as the recommended dose for the phase 3 portion — the ORR reached 50 percent, with two complete responses and a DCR of 80.6 percent. Importantly, efficacy was observed irrespective of CDH6 expression, the target antigen for the ADC, suggesting broad therapeutic potential.

Safety data indicated a manageable toxicity profile. The most frequent treatment-emergent adverse events included nausea, anemia, fatigue, and neutropenia. Grade ≥3 events occurred in 30.6 percent of patients at 5.6 mg/kg — a rate comparable to other ADCs currently in use. The most serious treatment-related concern remained interstitial lung disease (ILD)/pneumonitis, with four cases confirmed across all cohorts. One grade ≥3 ILD event was reported, reinforcing the need for vigilant monitoring as the program progresses to later stages.

The companies confirmed that the 5.6 mg/kg dose will advance into the pivotal phase 3 study, which aims to enroll approximately 700 patients globally. The trial will compare Raludotatug deruxtecan against investigator’s-choice chemotherapy, measuring progression-free survival (PFS) and overall survival (OS) as co-primary endpoints.

Why the results could reshape the competitive landscape for ADCs targeting ovarian and peritoneal cancers

The clinical success of Raludotatug deruxtecan could significantly alter the treatment paradigm in platinum-resistant ovarian cancer, where therapeutic progress has been limited despite decades of research. The drug represents a new generation of ADCs designed to deliver a cytotoxic payload directly to CDH6-expressing tumor cells, minimizing systemic exposure while intensifying tumor-specific lethality.

Analysts have drawn parallels to mirvetuximab soravtansine (ELAHERE®), approved for FRα-positive ovarian cancer, and trastuzumab deruxtecan (Enhertu®), another Daiichi Sankyo–Merck co-developed ADC targeting HER2. However, while ELAHERE® demonstrated an ORR of around 32 percent in its pivotal SORAYA study, Raludotatug deruxtecan has delivered response rates exceeding 50 percent — a differential that could redefine benchmarks for efficacy in refractory disease.

In terms of molecular design, Raludotatug deruxtecan utilizes Daiichi Sankyo’s proprietary DXd payload technology, the same platform underpinning Enhertu®. The conjugate’s optimized linker chemistry allows controlled drug release within tumor microenvironments, contributing to both potency and safety balance. Should phase 3 results confirm the phase 2 findings, this program may not only secure regulatory priority review but also expand the company’s ADC franchise across gynecologic indications.

For Merck & Co., the collaboration strengthens its oncology portfolio beyond immunotherapy, aligning with the strategic objective to diversify revenue streams beyond the Keytruda® franchise. Daiichi Sankyo, meanwhile, continues to leverage its ADC expertise to establish leadership across multiple tumor types, with R-DXd now emerging as one of its most promising pipeline assets.

How expert sentiment positions Raludotatug deruxtecan among next-generation ADCs in gynecologic oncology

Industry analysts and oncology researchers have pointed out that the magnitude of response observed in REJOICE-Ovarian01 is rare in platinum-resistant ovarian cancer, particularly in heavily pretreated cohorts. Experts commenting on the data suggested that Raludotatug deruxtecan could challenge the therapeutic dominance of FRα-targeted agents if its efficacy and tolerability remain consistent in phase 3.

Clinical investigators emphasized that CDH6, a cadherin family protein implicated in tumor progression and adhesion, offers a unique biological target that is overexpressed in several epithelial malignancies. Early evidence from translational studies suggests that targeting CDH6 may inhibit tumor growth and metastatic potential — a finding that could extend the drug’s reach beyond ovarian cancer into renal or pancreatic subtypes.

From an investor-sentiment standpoint, Raludotatug deruxtecan represents a potentially de-risked pipeline asset for both developers. Daiichi Sankyo’s market capitalization has historically been sensitive to ADC-related news flow, and the strong phase 2 data could sustain upward institutional interest. Similarly, Merck’s equity analysts viewed this collaboration as a critical diversification play, especially as Keytruda’s U.S. patent expiration looms later in the decade.

Although the ADC space is becoming increasingly crowded, Raludotatug deruxtecan’s tumor-agnostic activity profile and manageable safety could distinguish it as a competitive option in resistant cancers. The market for ovarian cancer therapeutics is projected to reach USD 10 billion by 2030, with ADCs accounting for a growing share as personalized medicine accelerates adoption.

What factors will determine whether Raludotatug deruxtecan achieves regulatory and commercial success after phase 3

The ultimate impact of Raludotatug deruxtecan will hinge on durability metrics such as median PFS, OS, and duration of response. While the 50 percent ORR marks a high-value inflection point, regulatory authorities will expect long-term evidence confirming that responses translate into meaningful survival benefit.

If phase 3 outcomes align with current efficacy while maintaining a manageable safety profile, analysts anticipate potential breakthrough therapy or accelerated approval filings in major markets. Moreover, because the drug’s efficacy appeared independent of CDH6 expression levels, companion diagnostic complexity may be reduced — a commercial advantage that could expand its addressable patient pool.

Beyond clinical performance, cost structure and manufacturing scalability will play pivotal roles. ADC production requires complex bioconjugation and stringent quality control, factors that influence pricing and reimbursement discussions. Merck and Daiichi Sankyo have already invested in global ADC manufacturing capacity, signaling readiness for commercial rollout should approval follow.

Investors will also monitor how this program integrates into the partners’ broader ADC alliances. Daiichi Sankyo’s multi-billion-dollar collaboration framework with Merck includes several candidates across solid tumors. Success with Raludotatug deruxtecan could catalyze further co-development milestones and revenue sharing through 2030 and beyond.

Strategic takeaway: could Raludotatug deruxtecan redefine how drug developers target platinum-resistant ovarian cancer?

The REJOICE-Ovarian01 results illustrate how targeted cytotoxic delivery is evolving beyond surface-antigen specificity into multi-tumor strategies anchored by linker-payload innovation. If validated in phase 3, Raludotatug deruxtecan may establish CDH6 as a credible oncology biomarker, reshape treatment sequencing in platinum-resistant ovarian cancer, and demonstrate the continued commercial viability of ADCs even as biologic competition intensifies.

For clinicians, the therapy could represent a meaningful option for patients who have exhausted platinum-based regimens, PARP inhibitors, and anti-angiogenic drugs. For investors, it underscores the structural importance of ADC pipelines within large-cap pharma growth models.

While caution remains warranted pending durability data, the early efficacy signals mark a tangible step toward transforming one of oncology’s most intractable diseases. The upcoming phase 3 readout — likely to capture global attention across both clinical and financial circles — may well determine whether this investigational ADC moves from promise to practice.