The ADC OQY-3258 Demonstrates Early Efficacy in Multiple Breast Cancer Subtypes

The investigational anti-TROP2 antibody-drug conjugate (ADC) OQY-3258 (ESG401) displayed preliminary activity in multiple breast cancer subtypes, according to findings from a phase 1a/1b trial (NCT04892342).

Data presented during the 2024 ESMO Congress demonstrated that patients with treatment-naive triple-negative breast cancer (TNBC; n = 25) achieved a confirmed overall response rate (ORR) of 76% and a disease control rate (DCR) of 100%.2 The median duration of response (DOR) and progression-free survival (PFS) had not yet been reached (NR). Findings from a January 2025 data cut showed that patients who received OQY-3258 (n = 35) experienced a confirmed ORR of 80%; the median DOR and PFS were still NR.1

Efficacy-evaluable patients with late-stage TNBC (n = 37) experienced a confirmed ORR of 27% and the DCR was 62%.2 The median DOR was 4.5 months (range, 3.1-13.6) and the 6-month DOR rate was 38.5% (95% CI, 12.0%-64.9%). Patients experienced a median PFS of 3.9 months (95% CI, 2.5-4.9) and the 6-month PFS rate was 25.3% (95% CI, 11.1%-39.6%).

Furthermore, efficacy-evaluable patients with late-stage hormone receptor (HR)–positive/HER2-negative breast cancer (n = 58) experienced a confirmed ORR of 29%. The median DOR was 8.0 months (range, 4.6-23.9) and the 6-month DOR rate was 70.0% (95% CI, 49.9%-90.1%). The median PFS was 7.4 months (95% CI, 3.7-9.2) and the 6-month PFS rate was 54.7% (95% CI, 41.4%-68.0%).

Findings from another abstract presented during the 2024 ESMO Congress showed that patients with efficacy-evaluable brain metastases and HER2-negative disease treated in the phase 1a/1b study (n = 17) experienced an intracranial ORR of 41% (95% CI, 18.4%-67.1%).3 The intracranial DCR was 76% (95% CI, 50.1%-93.2%) and the median PFS among these patients was 4.6 months (95% CI, 2.0-9.8).

“The compelling clinical activity demonstrated in our phase 1a/1b trial highlights the potential of OQY-3258 to address significant unmet needs in TROP2-expressing tumors,” Michael King, chief executive officer of Oqory, Inc, stated in a news release.1 “With its optimized serum-stable linker design, OQY-3258 has shown a markedly lower incidence of severe off-target toxicity compared with other marketed TROP2 therapies, positioning it as a differentiated late-stage ADC for metastatic breast cancer and other TROP2-expressing cancers.”

The open-label, dose-escalation, and cohort expansion study enrolled adult patients with solid tumors, including cervical, colorectal, endometrial, ovarian, esophageal, gastric, glioblastoma multiforme, head and neck, prostate, and pancreatic cancers, as well as non–small cell lung cancer, small cell lung cancer, non-TNBC, and TNBC.4 Eligible patients needed to have disease for which no effective standard therapy was available or tolerable, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ function.

During the dose escalation phase, patients received OQY-3258 at doses ranging from 2 mg/kg to 20 mg/kg every 3 weeks or from 12 mg/kg to 18 mg/kg on days 1, 8, and 15 of each 28-day cycle.2 In the dose expansion phase, all patients with breast cancer were treated on days 1, 8, and 15. Patients with TNBC who received at least 2 prior lines of therapy received the ADC at a dose of 12-, 14- or 16 mg/kg, those with HR-positive/​HER2-negative breast cancer were treated with 12 mg/kg or 16 mg/kg, and patients with TNBC received OQY-3258 at 16 mg/kg.

The coprimary end points were safety and ORR per independent central review.4 Secondary end points included PFS, overall survival, and ORR by local assessment.

Patients in the safety population (n = 144) experienced any-grade treatment-related adverse effects (TRAEs) at a rate of 97.9%; grade 3 or higher TRAEs (47.9%) and serious TRAEs (11.8%) were also reported.2 TRAEs leading to treatment discontinuation (2.1%), dose delay (38.2%), and dose reduction (6.3%) all occurred. No patients experienced TRAEs leading to death.

OQY-3258 is also being examined in 2 phase 3 clinical trials, one in patients with locally advanced or metastatic HR-positive/​HER2-negative breast cancer (NCT06383767) and in another as frontline treatment for patients with unrespectable recurrent or metastatic TNBC (NCT06732323).1 Data from the latter study led to OQY-3258’s receipt of Breakthrough Designation from China’s National Medical Products Administration in November 2024.

In the news release, Vincerx Pharma and Oqory also offered insights into their proposed strategic merger. The goal of the merger is to advance OQY-3258 into global phase 3 studies and to construct a differentiated ADC pipeline.

“The proposed merger with Oqory reflects our commitment to develop transformative therapies for patients with cancer,” Raquel Izumi, PhD, acting chief executive officer of Vincerx, added in the news release. “The promising efficacy and favorable safety profile demonstrated by OQY-3258 highlights its potential as a best-in-class anti-TROP2 ADC. By bringing together Vincerx’s development expertise and Oqory’s ADC technologies, we aim to accelerate the development of OQY-3258, while building a pipeline of next-generation ADCs that address significant unmet patient needs.”

References

1. Vincerx Pharma, Inc. and Oqory, Inc. highlight promising data for Oqory’s TROP2 antibody drug conjugate, OQY-3258. News release. Vincerx Pharma. January 29, 2025. Accessed January 29, 2025. https://investors.vincerapharma.com/news-releases/news-release-details/vincerx-pharma-inc-and-oqory-inc-highlight-promising-data-oqorys
2. Ma F, Qiu F, Tong Z, et al. Results from a phase Ia/Ib study of ESG401, a novel Trop2 antibody-drug conjugate, in patients with different subtypes of metastatic breast cancer. Ann Oncol. 2024;35(suppl 2):S361-S362. doi:10.1016/j.annonc.2024.08.297
3. Ma F, Qiu F, Tong Z, et al. ESG401, a novel Trop2 antibody-drug conjugate (ADC), and its efficacy evidence in HER2-negative metastatic breast cancer with brain metastases. Ann Oncol. 2024;35(suppl 2):S359. doi:10.1016/j.annonc.2024.08.292
4. Study of ESG401 in adults with solid tumors. ClinicalTrials.gov. Updated on April 30, 2024. Accessed January 29, 2025. https://clinicaltrials.gov/study/NCT04892342