At the ESMO Congress 2026, Ana Oaknin (Majadahonda, Spain) presented results from cohort B-1 of the phase Ib/II REJOICE-Ovarian02 trial (NCT06843447), evaluating raludotatug deruxtecan (R-DXd), a cadherin-6-targeted antibody–drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant recurrent ovarian cancer.
The investigational combination demonstrated promising preliminary antitumor activity, achieving a confirmed objective response rate (ORR) of 80% at the 4.8 mg/kg R-DXd dose, compared with 53% at 5.6 mg/kg. However, the small patient cohorts and a fatal interstitial lung disease event highlight the need for further efficacy and safety evaluation.
Methods
REJOICE-Ovarian02 is a phase Ib/II study evaluating the safety and preliminary efficacy of raludotatug deruxtecan, an ADC combining a humanized anti-cadherin-6 antibody with a topoisomerase I inhibitor payload, alongside bevacizumab.
The analysis included 30 patients with platinum-resistant high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received 1–3 prior lines of systemic therapy. Patients with primary platinum-refractory disease were excluded.
Patients received intravenous R-DXd at either 4.8 mg/kg (n=10) or 5.6 mg/kg (n=20), combined with bevacizumab 15 mg/kg every three weeks until disease progression or unacceptable toxicity.
The primary endpoints included dose-limiting toxicities, adverse events, and treatment discontinuations due to adverse events. Confirmed ORR assessed by blinded independent central review according to RECIST v1.1 was a secondary endpoint.
Key Takeaways
At the February 3, 2026, data cutoff, the median follow-up was 4.5 months.
- Confirmed objective response rate at 4.8 mg/kg: 80% (8/10; 95% CI, 44–98%), including one complete response and seven partial responses.
- Confirmed objective response rate at 5.6 mg/kg: 53% (8/15 response-evaluable patients; 95% CI, 27–79%), with eight partial responses.
- Disease control: All patients achieved disease control and experienced tumor shrinkage.
- Ongoing treatment: 25 of 30 patients remained on treatment at the data cutoff.
- Grade ≥3 adverse events: None occurred in the 4.8 mg/kg cohort, compared with 45% (9/20) in the 5.6 mg/kg cohort.
- Treatment interruptions: Adverse events led to treatment interruptions in 50% and 45% of patients at 4.8 mg/kg and 5.6 mg/kg, respectively.
- Treatment discontinuation: Adverse events led to discontinuation in 10% of patients in each dose cohort.
- Interstitial lung disease (ILD): One grade 1 drug-related ILD case occurred at 4.8 mg/kg. At 5.6 mg/kg, one fatal event initially assessed as aspiration pneumonia was subsequently adjudicated as drug-related ILD.
No dose-limiting toxicities or evidence of synergistic toxicity were reported. The overall safety profile was consistent with the known profiles of the individual treatments.
Conclusion
The REJOICE-Ovarian02 findings demonstrated encouraging preliminary antitumor activity with raludotatug deruxtecan plus bevacizumab in patients with platinum-resistant recurrent ovarian cancer.
The 80% confirmed response rate at 4.8 mg/kg, together with disease control across both dose cohorts, supports further investigation of this cadherin-6-targeted ADC combination. However, the small sample size and short follow-up limit conclusions about comparative efficacy and response durability.
Although no dose-limiting toxicities were observed, the fatal ILD event at the higher dose highlights an important safety concern requiring careful monitoring in subsequent studies.
Further clinical evaluation is needed to establish the optimal dose, long-term safety, and potential clinical benefit of R-DXd plus bevacizumab in platinum-resistant ovarian cancer.
Source: ESMO Congress 2026, Abstract 1247RO; REJOICE-Ovarian02 (NCT06843447).
